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Sample records for antioxidant resveratrol significantly

  1. An antioxidant resveratrol significantly enhanced replication of hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    Mitsuyasu; Nakamura; Masanori; Ikeda; Ryota; Hokari; Nobuyuki; Kato; Toshifumi; Hibi; Soichiro; Miura

    2010-01-01

    AIM:To elucidate the effect of antioxidants,resveratrol (RVT)and astaxanthin(AXN),on hepatitis C virus(HCV) replication. METHODS:We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6.RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses.AXN is also a strong antioxidant.The replication of HCV RNA was assessed by the luciferase reporter assay.An additive effect of antioxidants on antiviral effects of inter...

  2. Resveratrol inhibits LXRα-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction

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    Jin, So Hee; Yang, Ji Hye; Shin, Bo Yeon; Seo, Kyuhwa; Shin, Sang Mi [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Cho, Il Je, E-mail: skek023@dhu.ac.kr [MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan, Gyeongsangbukdo 712-715 (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2013-08-15

    Liver X receptor-α (LXRα), a member of the nuclear receptor superfamily of ligand-activated transcription factors, regulates de novo fatty acid synthesis that leads to stimulate hepatic steatosis. Although, resveratrol has beneficial effects on metabolic disease, it is not known whether resveratrol affects LXRα-dependent lipogenic gene expression. This study investigated the effect of resveratrol in LXRα-mediated lipogenesis and the underlying molecular mechanism. Resveratrol inhibited the ability of LXRα to activate sterol regulatory element binding protein-1c (SREBP-1c) and thereby inhibited target gene expression in hepatocytes. Moreover, resveratrol decreased LXRα–RXRα DNA binding activity and LXRE-luciferase transactivation. Resveratrol is known to activate Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK), although its precise mechanism of action remains controversial. We found that the ability of resveratrol to repress T0901317-induced SREBP-1c expression was not dependent on AMPK and Sirt1. It is well established that hepatic steatosis is associated with antioxidant and redox signaling. Our data showing that expression of Sestrin2 (Sesn2), which is a novel antioxidant gene, was significantly down-regulated in the livers of high-fat diet-fed mice. Moreover, resveratrol up-regulated Sesn2 expression, but not Sesn1 and Sesn3. Sesn2 overexpression repressed LXRα-activated SREBP-1c expression and LXRE-luciferase activity. Finally, Sesn2 knockdown using siRNA abolished the effect of resveratrol in LXRα-induced FAS luciferase gene transactivation. We conclude that resveratrol affects Sesn2 gene induction and contributes to the inhibition of LXRα-mediated hepatic lipogenesis. - Highlights: • We investigated the effect of resveratrol in LXRα-mediated lipogenesis. • Resveratrol attenuated the ability of the LXRα-mediated lipogenic gene expression. • Resveratrol’s effects on T090-induced lipogenesis is not dependent on Sirt1 or AMPK.

  3. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

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    Zhigang Zhang

    2014-01-01

    Full Text Available Resveratrol (Rev can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3 is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.

  4. Syntheses of Resveratrol Analogues and Evaluation of Their Antioxidant Activity

    International Nuclear Information System (INIS)

    Free radicals such as superoxide anion radicals (O2·-), hydroxyl radicals (·OH) and non-free radical species such as hydrogen peroxide (H2O2) and singlet oxygen (1O2) are considered as ROS. These ROS not only oxidize membrane lipids but damage nucleic acids, proteins and carbohydrates leading to mutations. If ROS are not scavenged by antioxidants, they could be involved in ageing and various diseases related to oxidative stress. Resveratrol is a natural phytoalexin found in the skin of grapes, red wines, and peanuts. It has three hydroxyl groups at the trans-stilbene structure, in which resorcinol and phenol are bridged by a trans double bond. The recent extensive studies on the resveratrol and its derivatives revealed that they have antioxidant, antimutagenic, antiinflammatory, antidiabetic, cardiovascular protective, and anticancer properties. It has been believed that the majority of the biological functions of resveratrol has been attributed to its antioxidant activity

  5. Resveratrol content and antioxidant properties of underutilized fruits.

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    Shrikanta, Akshatha; Kumar, Anbarasu; Govindaswamy, Vijayalakshmi

    2015-01-01

    In the present study, resveratrol content and antioxidant properties of underutilized fruits such as Jamun (Syzygium cumini L.), Jackfruit (Artocarpus heterophyllus) and Mulberry (Morus rubra) were investigated keeping Grape (Vitis vinifera) as a reference. Ethanol/water (80:20 v/v) extracts of different parts of fruit samples including skin, pulp and seeds were analyzed by HPLC and MS for the quantification of resveratrol. Total polyphenols, flavonoids, DPPH scavenging activity and total antioxidant capacity were also investigated. Among the samples analyzed, mulberry fruit (whole) showed highest resveratrol content (50.61 μg g(-1) dry weight) followed by jamun seed (34.87 μg g(-1) dry weight), jamun pulp (13.70 μg g(-1) dry weight) and skin of jamun (11.19 μg g(-1) dry weight). Jamun seed extract exhibited the highest polyphenol content (55.54 mg gallic acid equivalent g(-1) dry weight) and highest antioxidant property (IC50 value-0.40 mg ml(-1)). The results suggest that underutilized fruits high in resveratrol and other polyphenols can be used as functional beverages. PMID:25593373

  6. Syntheses of Resveratrol Analogues and Evaluation of Their Antioxidant Activity

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    Kim, Mi Jeong; Jung, Se Hoon; Moon, Insu; Jun Jonggab; Lee, Jeong Tae [Hallym Univ., Chuncheon (Korea, Republic of)

    2014-05-15

    Free radicals such as superoxide anion radicals (O{sub 2}·{sup -}), hydroxyl radicals (·OH) and non-free radical species such as hydrogen peroxide (H{sub 2}O{sub 2}) and singlet oxygen ({sup 1}O{sub 2}) are considered as ROS. These ROS not only oxidize membrane lipids but damage nucleic acids, proteins and carbohydrates leading to mutations. If ROS are not scavenged by antioxidants, they could be involved in ageing and various diseases related to oxidative stress. Resveratrol is a natural phytoalexin found in the skin of grapes, red wines, and peanuts. It has three hydroxyl groups at the trans-stilbene structure, in which resorcinol and phenol are bridged by a trans double bond. The recent extensive studies on the resveratrol and its derivatives revealed that they have antioxidant, antimutagenic, antiinflammatory, antidiabetic, cardiovascular protective, and anticancer properties. It has been believed that the majority of the biological functions of resveratrol has been attributed to its antioxidant activity.

  7. Resveratrol

    DEFF Research Database (Denmark)

    Vang, Ole

    2015-01-01

    Testing the biological activities of a dietary compound like resveratrol presents various challenges, which are highlighted in this commentary, with some suggested direction for future research, focusing on five challenges: (1) many different cellular effects are observed for resveratrol......, but it is not known whether they arise from one point of action (or a few) or whether resveratrol is non-specific in its action; (2) the health-promotion effect of dietary resveratrol is likely a combinatory effect of various bioactive components in the mixture (diet); (3) the known cell biological response...... to resveratrol is presently based on exposure to short-term high levels, and better in vitro analyses have to be developed; (4) the actual level of resveratrol and resveratrol metabolites present in vitro and in vivo during experiments may be over- and underestimated, respectively, because resveratrol...

  8. Resveratrol

    Science.gov (United States)

    Resveratrol is a chemical found in red wine, red grape skins, purple grape juice, mulberries, and in ... It is used as a medicine. People use resveratrol for "hardening of the arteries" (atherosclerosis), lowering "bad" ( ...

  9. In Vitro Protective Effect and Antioxidant Mechanism of Resveratrol Induced by Dapsone Hydroxylamine in Human Cells.

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    Rosyana V Albuquerque

    Full Text Available Dapsone (DDS hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV on DDS hydroxylamine (DDS-NHOH mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET, but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT activity and reactive oxygen species (ROS generation, but did not alter superoxide dismutase (SOD activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

  10. PTEN Mediates the Antioxidant Effect of Resveratrol at Nutritionally Relevant Concentrations

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    Marta Inglés

    2014-01-01

    Full Text Available Introduction. Antioxidant properties of resveratrol have been intensively studied for the last years, both in vivo and in vitro. Its bioavailability after an oral dose is very low and therefore it is very important to make sure that plasma concentrations of free resveratrol are sufficient enough to be active as antioxidant. Aims. In the present study, using nutritionally relevant concentrations of resveratrol, we aim to confirm its antioxidant capacity on reducing peroxide levels and look for the molecular pathway involved in this antioxidant effect. Methods. We used mammary gland tumor cells (MCF-7, which were pretreated with different concentrations of resveratrol for 48 h, and/or a PTEN inhibitor (bpV: bipy. Hydrogen peroxide levels were determined by fluorimetry, PTEN levels and Akt phosphorylation by Western Blotting, and mRNA expression of antioxidant genes by real-time reverse transcriptase-polymerase chain reaction (RT-PCR. Results. Resveratrol treatment for 48 h lowered peroxide levels in MCF-7, even at low nutritional concentrations (1 nM. This effect was mediated by the activation of PTEN/Akt pathway, which resulted in an upregulation of catalase and MnSOD mRNA levels. Conclusion. Resveratrol acts as an antioxidant at nutritionally relevant concentrations by inducing the expression of antioxidant enzymes, through a mechanism involving PTEN/Akt signaling pathway.

  11. Structural modeling for DNA binding to antioxidants resveratrol, genistein and curcumin.

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    N'soukpoé-Kossi, C N; Bourassa, P; Mandeville, J S; Bekale, L; Tajmir-Riahi, H A

    2015-10-01

    Several models are presented here for the bindings of the antioxidant polyphenols resveratrol, genistein and curcumin with DNA in aqueous solution at physiological conditions. Multiple spectroscopic methods and molecular modeling were used to locate the binding sites of these polyphenols with DNA duplex. Structural models showed that intercalation is more stable for resveratrol and genistein than groove bindings, while curcumin interaction is via DNA grooves. Docking showed more stable complexes formed with resveratrol and genistein than curcumin with the free binding energies of -4.62 for resveratrol-DNA (intercalation), -4.28 for resveratrol-DNA (groove binding), -4.54 for genistein-DNA (intercalation), -4.38 for genistein-DNA (groove binding) and -3.84 kcal/mol for curcumin-DNA (groove binding). The free binding energies show polyphenol-DNA complexation is spontaneous at room temperature. At high polyphenol concentration a major DNA aggregation occurred, while biopolymer remained in B-family structure. PMID:26188387

  12. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

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    Allan Lançon

    2016-03-01

    Full Text Available Resveratrol (3,4′,5 trihydroxy-trans-stilbene is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.

  13. Improved Antioxidant Capacity of Optimization of a Self-Microemulsifying Drug Delivery System for Resveratrol

    OpenAIRE

    Ying Chen; Huiyong Zhang; Jing Yang; Haiyan Sun

    2015-01-01

    The use of nano-encapsulated resveratrol (RSV) in self-micro-emulsified drug delivery systems (SMEDDS) formulations was investigated. Self-emulsifying grading tests were used to establish the optimal ratio of oil, surfactant, and co-surfactant. The optimized system was further investigated for the droplet size and zeta potential at the different medium pH values by a Malvern Zetasizer and transmission electron microscopy (TEM). The antioxidant capacity and cytotoxicity of the formulation were...

  14. Physicochemical properties and antioxidant potential of phosvitin-resveratrol complexes in emulsion system.

    Science.gov (United States)

    Duan, Xiang; Li, Mei; Ma, Huijie; Xu, Xueming; Jin, Zhengyu; Liu, Xuebo

    2016-09-01

    Egg yolk phosvitin is the most highly phosphorylated protein found in the nature. The physicochemical properties of phosvitin-resveratrol complexes and their synergistic antioxidant activities in microemulsions were investigated. The particle diameters of microemulsions containing 0.5%, 1.0% and 2.0% phosvitin were 2.660, 0.501 and 0.414μm, respectively. The emulsifying activity index increased largely from 3.72 to 21.5m(2)/g with increasing phosvitin concentration from 0.5% to 2.0%. Fourier transform infrared spectroscopy and thermal analyses indicated that the microemulsions underwent a conformational change during homogenization. Antioxidant assays showed that phosvitin-resveratrol microemulsions exhibited a higher antioxidant activity than that of phosvitin-resveratrol primary emulsions. The MTT assay indicated that HepG2 cell viability remained higher than 80% at phosvitin concentration below 1.0mg/ml. This suggested that phosvitin, when coupled with polyphenol, can effectively inhibit lipid oxidation in food emulsions, which provided valuable insights into deep processing and application of egg proteins in food industry. PMID:27041304

  15. A randomized clinical study assessing the effects of the antioxidants, resveratrol or SG1002, a hydrogen sulfide prodrug, on idiopathic oligoasthenozoospermia

    Institute of Scientific and Technical Information of China (English)

    Arturo Morales Martinez; Luis H. Sordia-Hernández; Juan A. Morales; Martha Merino; Oscar Vidal; Manuel R. García Garza; Otto Valdés

    2015-01-01

    Objective: To determine whether subjects suffering from oligoasthenozoospermia would benefit from antioxidant treatment with resveratrol, a natural-occurring polyphenol, and hydrogen sulfide. Methods: A randomized controlled clinical trial involving 54 men with Oligoasthenozoospermia. We randomly assigned resveratrol (n=18), SG 1002 (n=18), and placebo (n=18) for 75 days. Sperm analysis was performed after treatment. Statistical analysis was made with chi square test. Results: When compared to the placebo treated group, SG1002 treatment led to an increase in sperm concentration (11.18 í 106 vs. 17.01 í 106, P < 0.05), sperm motility (10.06 í 106 vs. 20.06 í 106, P<0.05) and motile forms recovery (0.33 í 106 vs. 1.62 í 106, P<0.05). Resveratrol treatment did not significantly affect any of the parameters. Conclusions: SG1002 may reverse oligoasthenozoospermia. It seems to be more potent antioxidant than resveratrol. This findings need be supported by further clinical investigation.

  16. ANTIOXIDANT EFFECT OF RESVERATROL IN HUMAN SPERMATOZOA AND IN RAT GERMINAL CELLS

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    MG. Federico

    2012-01-01

    Full Text Available Objective: To assess the antioxidant activity of Resveratrol (3,5,4’-trihydroxystilbene, RES after induction of lipid peroxidation LPO in human spermatozoa and in immature rat germinal cells. Materials and Methods: Ejaculated human spermatozoa, selected by swim up, have been incubated with tert-Butylhydroperoxide and tert-Butylhydroperoxide-RES. The localization of LPO has been performed using the probe C11-BODIPY581/591. The same assays were carried out on pachytene spermatocytes and round spermatids obtained from three Wistar rats 35 days of age. The two cellular fractions were achieved after enzymatic digestion with collagenase and subsequent fractionation on bovine serum albumin 0.5-3% gradient (STAPUT. The ultrastructure of all samples was assessed by transmission electron microscopy (TEM. Results: The midpiece of sperm tail and the whole plasma membrane of germ cells were the target of LPO. TEM analysis of sperm, quantitatively elaborated by a mathematical formula, showed a significantly lower percentage of necrosis in the samples treated with RES (P<0.01; as regards rat germinal cells, necrosis features (cytoplasmic vacuoles, disrupted chromatin and broken plasma membrane were mainly evident in the meiotic fraction without RES. Conclusions: RES, found in the skins of grape, reduces the damage induced by oxidative stress in human sperm and rat testicular germ cells; in particular spermatids appeared to be less sensitive to oxidative damage compared with spermatocytes.

  17. Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice

    International Nuclear Information System (INIS)

    The present study was designed to examine the antioxidative effect of curcumin, resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and cadmium distribution in an experimental model in mice. Male CD mice were treated once daily for 3 days with curcumin (50 mg/kg b.w., p.o.), resveratrol (20 mg/kg b.w., p.o.) or melatonin (12 mg/kg, p.o.), dispersed in 0.5% methylcellulose. One hour after the last dose of antioxidants cadmium chloride was administered (7 mg/kg b.w., s.c.) to pre-treated animals and control animals receiving methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP - expressed as malondialdehyde production), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates. Cadmium concentration was measured in the liver, kidneys, testes and brain by AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation (to 133%, p < 0.001), decreased GSH content (to 65%, p < 0.001) and inhibited catalase (to 68%, p < 0.001) and GPx activity (to 60%, p < 0.001) in the liver. Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity. Resveratrol was effective against Cd-induced inhibition of catalase activity (p < 0.001). The decrease in hepatic GSH level was not prevented by curcumin, resveratrol or melatonin pre-treatment. In mice treated with antioxidants alone the level of LP, GSH, GPx or CAT was not different from control levels. The pre-treatment with antioxidants did not affect cadmium distribution in the tissues of Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and melatonin pre-treatment effectively protect against cadmium-induced lipid peroxidation and ameliorate the adverse effect of cadmium on antioxidant status without any reduction in tissue Cd burden

  18. Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes.

    Science.gov (United States)

    Fabris, Sabrina; Momo, Federico; Ravagnan, Giampietro; Stevanato, Roberto

    2008-06-01

    The antioxidant activities of trans-resveratrol (trans-3,5,4'-trihydroxystilbene) and trans-piceid (trans-5,4'-dihydroxystilbene-3-O-beta-D-glucopyranoside), its more widespread glycosilate derivative, have been compared measuring their inhibitory action on peroxidation of linoleic acid (LA) and the radical scavenging ability towards different free radicals (such as DPPH) and radical initiators. It has been found that the two stilbenes have similar antioxidant capacity, while the comparison with BHT (2,6-di-tert-butyl-4-methylphenol) and alpha-tocopherol (vitamin E, vit. E), taken as reference, points out a slower but prolonged protective action against lipid peroxidation. Furthermore, piceid appears more efficacious than resveratrol as a consequence of the reaction of the latter with its radical form. The DSC profiles of phosphatidylcholine liposomes of various chain lengths, and EPR measurements of spin labelled liposomes demonstrated that the susceptible hydroxyl group of these compounds are located in the lipid region of the bilayer close to the double bonds of polyunsaturated fatty acids, making these stilbenes particularly suitable for the prevention and control of the lipid peroxidation of the membranes.

  19. Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia patients.

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    Fibach, Eitan; Prus, Eugenia; Bianchi, Nicoletta; Zuccato, Cristina; Breveglieri, Giulia; Salvatori, Francesca; Finotti, Alessia; Lipucci di Paola, Michele; Brognara, Eleonora; Lampronti, Ilaria; Borgatti, Monica; Gambari, Roberto

    2012-06-01

    Thalassemia and sickle-cell anemia (SCA) present a major public health problem in countries where the number of carriers and affected individuals is high. As a result of the abnormalities in hemoglobin production, cells of thalassemia and SCA patients exhibit oxidative stress, which ultimately is responsible for the chronic anemia observed. Therefore, identification of compounds exhibiting both antioxidant and hemoglobin-inducing activities is highly needed. Our results demonstrate resveratrol to be such a compound. This was shown both in the human K562 cell line, as well as in erythroid precursors derived from normal donors and β-thalassemia patients. Resveratrol was shown to exhibit antioxidant activity and to stimulate the expression of the γ-globin genes and the accumulation of fetal hemoglobin (HbF). To the best of our knowledge, this is the first report pointing to such a double effect of resveratrol. Since this natural product is already marketed as an antioxidant, future investigations should concentrate on demonstrating its potential to augment HbF production in experimental animal models (e.g., thalassemia and SCA mice) as well as in patients. We believe that the potential of clinical use of resveratrol as an antioxidant and HbF stimulator may offer a simple and inexpensive treatment to patients.

  20. Locating the binding sites of antioxidants resveratrol, genistein and curcumin with tRNA.

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    N'soukpoé-Kossi, C N; Bourassa, P; Mandeville, J S; Bekale, L; Bariyanga, J; Tajmir-Riahi, H A

    2015-09-01

    We located the binding sites of antioxidants resveratrol, genistein and curcumin on tRNA in aqueous solution at physiological conditions using constant tRNA concentration and various polyphenol contents. FTIR, UV-visible, CD spectroscopic methods and molecular modeling were used to determine polyphenol binding sites, the binding constant and the effects of polyphenol complexation on tRNA conformation and particle formation. Structural analysis showed that polyphenols bind tRNA via G-C and A-U base pairs through hydrophilic, hydrophobic and H-bonding contacts with overall binding constants of K(res-tRNA)=8.95(±0.80)×10(3) M(-1), K(gen-tRNA)=3.07(±0.5)×10(3) M(-1) and K(cur-tRNA)=1.55(±0.3)×10(4) M(-1). Molecular modeling showed the participation of several nucleobases in polyphenol-tRNA adduct formation with free binding energy of -4.43 for resveratrol, -4.26 kcal/mol for genistein and -4.84 kcal/mol for curcumin, indicating that the interaction process is spontaneous at room temperature. While tRNA remains in A-family structure, major biopolymer aggregation and particle formation occurred at high polyphenol contents. PMID:26093317

  1. Potential of the Dietary Antioxidants Resveratrol and Curcumin in Prevention and Treatment of Hematologic Malignancies

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    Marc Diederich

    2010-10-01

    Full Text Available Despite considerable improvements in the tolerance and efficacy of novel chemotherapeutic agents, the mortality of hematological malignancies is still high due to therapy relapse, which is associated with bad prognosis. Dietary polyphenolic compounds are of growing interest as an alternative approach, especially in cancer treatment, as they have been proven to be safe and display strong antioxidant properties. Here, we provide evidence that both resveratrol and curcumin possess huge potential for application as both chemopreventive agents and anticancer drugs and might represent promising candidates for future treatment of leukemia. Both polyphenols are currently being tested in clinical trials. We describe the underlying mechanisms, but also focus on possible limitations and how they might be overcome in future clinical use – either by chemically synthesized derivatives or special formulations that improve bioavailability and pharmacokinetics.

  2. Evaluation of free radical scavenging capacity and antioxidative damage effect of resveratrol-nanostructured lipid carriers

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    Jin, Ju; Shi, Fan; Li, Qiu-wen; Li, Pei-shan; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Cellular damage induced by free-radicals like reactive oxygen species has been implicated in several diseases. 2, 2-azobis(2-amidino-propane) dihydrochloride(AAPH) generates two potent ROS capable of inducing lipid peroxidation: alkoxy radical(RO-) and peroxy radical(ROO-). These radicals are similar to those that are physiologically active and thus might initiate a cascade of intracellular toxic events leading to oxidation, lipid peroxidation, DNA damage and subsequent cell death. Hence naturally anti-oxidant play a vital role in combating these conditions. In this study, resveratrol loaded nanostructured lipid carriers (Res-NLC) was prepared by hot melting and then high pressure homogenization technique. The effects of Res-NLC on free radical scavenging capacity and antioxidative damage is investigated. The particle size and zeta potential of Res-NLC were 139.3 ± 1.7 nm and -11.21 ± 0.41 mV, respectively. By free radical scavenging assays, the IC50 value of Res-NLC were 19.25, 5.29 μg/mL with DPPH, ABTS assay respectively, and 0.161 mg ferrous sulfate/1 mg Res-NLC with FRAP assay; and by AAPH-induced oxidative injury cell model assay, Res-NLC showed the strong protective effect against the human liver tumor HepG2 cell oxidative stress damage. These results indicated that the antioxidant properties of Res-NLC hold great potential used as an alternative to more toxic synthetic antioxidants as an additive in food, cosmetic and pharmaceutical preparations for the oxidative diseases treatment.

  3. Improved Antioxidant Capacity of Optimization of a Self-Microemulsifying Drug Delivery System for Resveratrol.

    Science.gov (United States)

    Chen, Ying; Zhang, Huiyong; Yang, Jing; Sun, Haiyan

    2015-01-01

    The use of nano-encapsulated resveratrol (RSV) in self-micro-emulsified drug delivery systems (SMEDDS) formulations was investigated. Self-emulsifying grading tests were used to establish the optimal ratio of oil, surfactant, and co-surfactant. The optimized system was further investigated for the droplet size and zeta potential at the different medium pH values by a Malvern Zetasizer and transmission electron microscopy (TEM). The antioxidant capacity and cytotoxicity of the formulation were detected by DCFH-DA and a CCK-8 assays. The results showed that the nano-emulsion based on ethyl oleate, Tween-80, and PEG-400 (35:40:25, w/w/w) was the most stable formulation due to the small droplet size (approximately 50 nm) and high zeta potential in a neutral environment. Furthermore, this formulation also exhibited a greater antioxidant capacity with less toxicity than free RSV. Taken together, considering these results and the simple fabrication process, this formulation could be used to deliver nutritional food supplements in a stable, efficient, and safe manner. PMID:26633319

  4. Improved Antioxidant Capacity of Optimization of a Self-Microemulsifying Drug Delivery System for Resveratrol

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    Ying Chen

    2015-11-01

    Full Text Available The use of nano-encapsulated resveratrol (RSV in self-micro-emulsified drug delivery systems (SMEDDS formulations was investigated. Self-emulsifying grading tests were used to establish the optimal ratio of oil, surfactant, and co-surfactant. The optimized system was further investigated for the droplet size and zeta potential at the different medium pH values by a Malvern Zetasizer and transmission electron microscopy (TEM. The antioxidant capacity and cytotoxicity of the formulation were detected by DCFH-DA and a CCK-8 assays. The results showed that the nano-emulsion based on ethyl oleate, Tween-80, and PEG-400 (35:40:25, w/w/w was the most stable formulation due to the small droplet size (approximately 50 nm and high zeta potential in a neutral environment. Furthermore, this formulation also exhibited a greater antioxidant capacity with less toxicity than free RSV. Taken together, considering these results and the simple fabrication process, this formulation could be used to deliver nutritional food supplements in a stable, efficient, and safe manner.

  5. Enhancement of phenolics, resveratrol and antioxidant activity by nitrogen enrichment in cell suspension culture of Vitis vinifera.

    Science.gov (United States)

    Sae-Lee, Napaporn; Kerdchoechuen, Orapin; Laohakunjit, Natta

    2014-01-01

    Ammonium nitrate (NH4NO3), an important nitrogen source (34% N), has been used as an elicitor to stimulate plant growth and development as well as induce secondary metabolites under controlled conditions. In the present paper, we investigated the enhancement of cell biomass, total phenolics, resveratrol levels, and antioxidant activity of Vitis vinifera cv. Pok Dum by nitrogen enrichment (MS medium supplemented with NH4NO3 at 0, 500, 1,000, 5,000 and 10,000 mg/L). The highest accumulations of biomass, phenolics and resveratrol contents were observed at 8.8-fold (86.6 g DW/L), 15.9-fold (71.91 mg GAE/g DW) and 5.6-fold (277.89 µg/g DW) by the 14th day, in the medium supplemented with 500 mg/L NH4NO3. Moreover, the antioxidant activities of cultured grape cells estimated by the DPPH· and ABTS·+ assay were positively correlated with phenolics and resveratrol, and the maximum activity was also observed in cultured cells with 500 mg/L NH4NO3 at 176.11 and 267.79 mmol TE/100 g DW, respectively. PMID:24962393

  6. Enhancement of Phenolics, Resveratrol and Antioxidant Activity by Nitrogen Enrichment in Cell Suspension Culture of Vitis vinifera

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    Napaporn Sae-Lee

    2014-06-01

    Full Text Available Ammonium nitrate (NH4NO3, an important nitrogen source (34% N, has been used as an elicitor to stimulate plant growth and development as well as induce secondary metabolites under controlled conditions. In the present paper, we investigated the enhancement of cell biomass, total phenolics, resveratrol levels, and antioxidant activity of Vitis vinifera cv. Pok Dum by nitrogen enrichment (MS medium supplemented with NH4NO3 at 0, 500, 1,000, 5,000 and 10,000 mg/L. The highest accumulations of biomass, phenolics and resveratrol contents were observed at 8.8-fold (86.6 g DW/L, 15.9-fold (71.91 mg GAE/g DW and 5.6-fold (277.89 µg/g DW by the 14th day, in the medium supplemented with 500 mg/L NH4NO3. Moreover, the antioxidant activities of cultured grape cells estimated by the DPPH· and ABTS·+ assay were positively correlated with phenolics and resveratrol, and the maximum activity was also observed in cultured cells with 500 mg/L NH4NO3 at 176.11 and 267.79 mmol TE/100 g DW, respectively.

  7. Isolation and purification of two antioxidant isomers of resveratrol dimer from the wine grape by counter-current chromatography.

    Science.gov (United States)

    Kong, Qingjun; Ren, Xueyan; Hu, Ruilin; Yin, Xuefeng; Jiang, Guoshan; Pan, Yuanjiang

    2016-06-01

    Resveratrol dimers belong to a group of compounds called stilbenes, which along with proanthocyanidins, anthocyanins, catechins, and flavonols are natural phenolic compounds found in grapes and red wine. Stilbenes have a variety of structural isomers, all of which exhibit various biological properties. Counter-current chromatography with a two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water (2:5:4:5, v/v/v/v) was applied to isolate and purify stilbene from the stems of wine grape. Two isomers of resveratrol dimers trans-ε-viniferin and trans-δ-viniferin were obtained from the crude sample in a one-step separation, with purities of 93.2 and 97.5%, respectively, as determined by high-performance liquid chromatography. The structures of these two compounds were identified by (1) H and (13) C NMR spectroscopy. In addition, their antioxidant activities were assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The antioxidant activities of trans-δ-viniferin were higher than that of trans-ε-viniferin in this model. This work demonstrated that counter-current chromatography is a powerful and effective method for the isolation and purification of polyphenols from wine grape. Additionally, the DPPH radical assay showed that the isolated component trans-δ-viniferin exhibited stronger antioxidant activities than trans-ε-viniferin and a little bit weaker than vitamin E at the same concentration. PMID:27130423

  8. Ovarian actions of resveratrol.

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    Ortega, Israel; Duleba, Antoni J

    2015-08-01

    Resveratrol, a natural polyphenol found in grapes, berries, and medicinal plants, exhibits antioxidant and anti-inflammatory activities and has been proposed to be a longevity-prolonging agent. There is also growing evidence that resveratrol has cardioprotective properties and beneficial effects on both glucose and lipid metabolism. Recently, several studies have examined the use of resveratrol as a therapeutic agent to treat numerous pathological and metabolic disorders. Herein, we present insights into the mechanisms of action, biological effects, and current evidence of actions of resveratrol on the ovary. In vitro, resveratrol inhibits proliferation and androgen production by theca-interstitial cells. Resveratrol also exerts a cytostatic, but not cytotoxic, effect on granulosa cells, while decreasing aromatization and vascular endothelial growth factor expression. In vivo, resveratrol treatment reduced the size of adipocytes and improved estrus cyclicity in the previously acyclic rat model of polycystic ovary syndrome (PCOS). In addition, resveratrol increased the ovarian follicular reserve and prolonged the ovarian life span in rats. Taken together, resveratrol emerges as a potential therapeutic agent to treat conditions associated with androgen excess, such as PCOS. The efficacy of resveratrol in the treatment of gynecological conditions requires further investigation. PMID:26315293

  9. Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

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    Shraddha D. Rege

    2013-01-01

    Full Text Available Resveratrol (3,5,4′-trihydroxy-trans-stilbene is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice.

  10. Effect of resveratrol on alcohol-induced mortality and liver lesions in mice

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    Hijona Elisabeth

    2006-11-01

    Full Text Available Abstract Background Resveratrol is a polyphenol with important antiinflammatory and antioxidant properties. We investigated the effect of resveratrol on alcohol-induced mortality and liver lesions in mice. Methods Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol. Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. The animals had free access to standard diet. Blood levels were determined for transaminases, IL-1 and TNF-α. A histological evaluation was made of liver damage, and survival among the animals was recorded. Results Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p Conclusion The results obtained suggest that resveratrol reduces mortality and liver damage in mice.

  11. Acuminatol and Other Antioxidative Resveratrol Oligomers from the Stem Bark of Shorea acuminata

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    Norhayati Muhammad

    2012-07-01

    Full Text Available A new resveratrol dimer, acuminatol (1, was isolated along with five known compounds from the acetone extract of the stem bark of Shorea acuminata. Their structures and stereochemistry were determined by spectroscopic methods, which included the extensive use of 2D NMR techniques. All isolated compounds were evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging activity (RSA and the β-carotene-linoleic acid (BCLA assays, and compared with those of the standards of ascorbic acid (AscA and butylated hydroxytoluene (BHT. All compounds tested exhibited good to moderate antioxidant activity in the DPPH assay (IC50s 0.84 to 10.06 mM and displayed strong inhibition of β-carotene oxidation (IC50s 0.10 to 0.22 mM. The isolated compounds were evaluated on the Vero cell line and were found to be non-cytotoxic with LC50 values between 161 to 830 µM.

  12. Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications

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    Sandri G

    2012-04-01

    Full Text Available Evren H Gokce1, Emrah Korkmaz1, Eleonora Dellera2, Giuseppina Sandri2, M Cristina Bonferoni2, Ozgen Ozer11Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ege, Izmir, Turkey; 2Department of Drug Sciences, University of Pavia, Pavia, ItalyBackground: Excessive generation of radical oxygen species (ROS is a contributor to skin pathologies. Resveratrol (RSV is a potent antioxidant. Solid lipid nanoparticles (SLN and nanostructured lipid carriers (NLC can ensure close contact and increase the amount of drug absorbed into the skin. In this study, RSV was loaded into SLN and NLC for dermal applications.Methods: Nanoparticles were prepared by high shear homogenization using Compritol 888ATO, Myglyol, Poloxamer188, and Tween80. Particle size (PS, polydispersity index (PI, zeta potential (ZP, drug entrapment efficiency (EE, and production yield were determined. Differential scanning calorimetry (DSC analysis and morphological transmission electron microscopy (TEM examination were conducted. RSV concentration was optimized with cytotoxicity studies, and net intracellular accumulation of ROS was monitored with cytofluorimetry. The amount of RSV was determined from different layers of rat abdominal skin.Results: PS of uniform RSV-SLN and RSV-NLC were determined as 287.2 nm ± 5.1 and 110.5 nm ± 1.3, respectively. ZP was –15.3 mV ± 0.4 and –13.8 mV ± 0.1 in the same order. The drug EE was 18% higher in NLC systems. TEM studies showed that the drug in the shell model was relevant for SLN, and that the melting point of the lipid in NLC was slightly lower. Concentrations below 50 µM were determined as suitable RSV concentrations for both SLN and NLC in cell culture studies. RSV-NLC showed less fluorescence, indicating less ROS production in cytofluorometric studies. Ex vivo skin studies revealed that NLC are more efficient in carrying RSV to the epidermis.Conclusion: This study suggests that both of the lipid nanoparticles had

  13. Resveratrol enhances antitumor activity of TRAIL in prostate cancer xenografts through activation of FOXO transcription factor.

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    Suthakar Ganapathy

    Full Text Available BACKGROUND: Resveratrol (3, 4', 5 tri-hydroxystilbene, a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining and inducing apoptosis (TUNEL staining. The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells and markers of metastasis (MMP-2 and MMP-9. The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. CONCLUSIONS/SIGNIFICANCE: These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.

  14. Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Phyu, Hnin Ei; Irwin, Jordon Candice; Vella, Rebecca Kate; Fenning, Andrew Stuart

    2016-06-01

    Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (Pheart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus. PMID:27153202

  15. Biological effects of resveratrol.

    Science.gov (United States)

    Frémont, L

    2000-01-14

    Resveratrol (3, 4', 5 trihydroxystilbene) is a naturally occuring phytoalexin produced by some spermatophytes, such as grapevines, in response to injury. Given that it is present in grape berry skins but not in flesh, white wine contains very small amounts of resveratrol, compared to red wine. The concentrations in the form of trans- and cis- isomers of aglycone and glucosides are subjected to numerous variables. In red wine, the concentrations of the trans-isomer, which is the major form, generally ranges between 0.1 and 15 mg/L. As phenolic compound, resveratrol contributes to the antioxidant potential of red wine and thereby may play a role in the prevention of human cardiovascular diseases. Resveratrol has been shown to modulate the metabolism of lipids, and to inhibit the oxidation of low-density lipoproteins and the aggregation of platelets. Moreover, as phytoestrogen, resveratrol may provide cardiovascular protection. This compound also possesses anti-inflammatory and anticancer properties. However, the bioavailability and metabolic pathways must be known before drawing any conclusions on the benefits of dietary resveratrol to health.

  16. Resveratrol and Myopathy.

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    Bastin, Jean; Djouadi, Fatima

    2016-01-01

    Resveratrol is a natural polyphenolic compound produced by plants under various stress conditions. Resveratrol has been reported to exhibit antioxidant, anti-inflammatory, and anti-proliferative properties in mammalian cells and animal models, and might therefore exert pleiotropic beneficial effects in different pathophysiological states. More recently, resveratrol has also been shown to potentially target many mitochondrial metabolic pathways, including fatty acid β-oxidation or oxidative phosphorylation, leading to the up-regulation of the energy metabolism via signaling pathways involving PGC-1α, SIRT1, and/or AMP-kinase, which are not yet fully delineated. Some of resveratrol beneficial effects likely arise from its cellular effects in the skeletal muscle, which, surprisingly, has been given relatively little attention, compared to other target tissues. Here, we review the potential for resveratrol to ameliorate or correct mitochondrial metabolic deficiencies responsible for myopathies, due to inherited fatty acid β-oxidation or to respiratory chain defects, for which no treatment exists to date. We also review recent data supporting therapeutic effects of resveratrol in the Duchenne Muscular Dystrophy, a fatal genetic disease affecting the production of muscle dystrophin, associated to a variety of mitochondrial dysfunctions, which likely contribute to disease pathogenesis. PMID:27136581

  17. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol.

    Science.gov (United States)

    Banu, Sakhila K; Stanley, Jone A; Sivakumar, Kirthiram K; Arosh, Joe A; Burghardt, Robert C

    2016-07-15

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in >50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50ppm potassium dichromate) from postpartum days 1-21 through drinking water with or without RVT (10mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E2) biosynthesis and enhancing metabolic clearance of E2, increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E2 levels by inhibiting hydroxylation, glucuronidation and sulphation of E2. This is the first study to report the protective effects of RVT against any toxicant in the ovary. PMID:27129868

  18. Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction

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    Seo, Kyuhwa; Seo, Suho; Han, Jae Yun; Ki, Sung Hwan; Shin, Sang Mi, E-mail: smshin@chosun.ac.kr

    2014-10-15

    Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. - Highlights: • Resveratrol decreased methylglyoxal-induced apoptosis. • Resveratrol attenuated GSH depletion and ROS production promoted by methylglyoxal. • Resveratrol restored the mitochondrial function by Sestrin2 induction. • Induction of Sestrin2

  19. Resveratrol: A Multifunctional Compound Improving Endothelial Function

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    Li, Huige; Förstermann, Ulrich

    2009-01-01

    The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

  20. Toxicogenomics of resveratrol in rat liver.

    Science.gov (United States)

    Hebbar, Vidya; Shen, Guoxiang; Hu, Rong; Kim, Bok-Ryang; Chen, Chi; Korytko, Peter J; Crowell, James A; Levine, Barry S; Kong, A-N Tony

    2005-04-01

    Resveratrol, a polyphenolic compound found in grape skin and peanuts has been shown to prevent many diseases including cardiovascular diseases and cancer. To better understand resveratrol's potential in vivo toxicity, we studied the dose response using cDNA stress arrays coupled with drug metabolizing enzymatic (DME) assays to investigate the expression of stress-responsive genes and Phase I and II detoxifying enzymes in rat livers. Male and female CD rats were treated with high doses of resveratrol (0.3, 1.0 and 3.0 gm/kg/day) for a period of 28 days. Total RNA from rat liver was reverse-transcribed using gene-specific primers and hybridized to stress-related cDNA arrays. Among female rats, Phase I DME genes were repressed at 0.3 and 1.0 gm/kg/day doses, while genes such as manganese superoxide dismutase, cytochrome P450 reductase, quinone oxidoreductase and thiosulfate sulfurtransferase demonstrated a dose-dependent increase in gene expression. The modulation of these liver genes may implicate the potential toxicity as observed among the rats at the highest dose level of resveratrol. Real-Time PCR was conducted on some of the Phase II DME genes and anti-oxidant genes to validate the cDNA array data. The gene expression from real-time PCR demonstrated good correlation with the cDNA array data. UGT1A genes were amongst the most robustly induced especially at the high doses of resveratrol. We next performed Phase I and Phase II enzymatic assays on cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1), NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Induction of Phase II detoxifying enzymes was most pronounced at the highest dose of resveratrol. CYP1A1 activity demonstrated a decreasing trend among the 3 dose groups and CYP2E1 activity increased marginally among female rats over controls. In summary, at lower doses of resveratrol there are few significant changes in gene expression whereas the

  1. Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction.

    Science.gov (United States)

    Bellaver, Bruna; Bobermin, Larissa Daniele; Souza, Débora Guerini; Rodrigues, Marília Danielly Nunes; de Assis, Adriano Martimbianco; Wajner, Moacir; Gonçalves, Carlos-Alberto; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-09-01

    Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and, neuroprotective effects. Resveratrol also plays a significant role modulating glial functionality, protecting the health of neuroglial cells against several neuropsychiatric in vivo and in vitro experimental models. Mitochondrial impairment strongly affected astrocyte functions and consequently brain homeostasis. Molecules that promote astrocyte mitochondrial protection are fundamental to maintain brain energy balance and cellular redox state, contributing to brain healthy. Thus, the present study was designed to evaluate some glioprotective mechanisms of resveratrol against mitochondrial damage promoted by azide exposure in hippocampal primary astrocyte cultures. Azide treatment provoked deleterious effects, including the dysfunction of mitochondria, the deterioration of redox homeostasis, the augmentation of pro-inflammatory cytokines and impairment of glutamate uptake activity. However, resveratrol prevented these effects, protecting hippocampal astrocytes against azide-induced cytotoxicity through the heme-oxygenase-1 (HO-1) pathway and inhibiting p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NFκB) activation. Resveratrol also protected astrocytes via phosphatidylinositide 3-kinase (PI3K)/Akt. These results contribute to the comprehension of the mechanisms by which resveratrol mediates hippocampal astrocyte protection against mitochondrial failure and implicate resveratrol as an important glioprotective molecule. PMID:27373419

  2. Resveratrol and its biological actions

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    Shah Praharsh

    2010-01-01

    Full Text Available Resveratrol is a phytoalexin that is found in a few edible food materials such as grape skins, pea-nuts and red wine. Numerous reports exists in the literature suggesting that dietary resveratrol may act as an antioxidant, promotes nitric oxide production, inhibits platelet aggregation and increases high-density lipoprotein cholesterol, and subsequently may serve as a cardio-protective agent. Recent reports demonstrated that resveratrol can function as a cancer chemopreventive agent, exhibiting anti-inflammatory, neuroprotective, anti-ageing and antiviral properties. However, most of these effects are yet to be confirmed in humans. In the only clinical trial, high doses of special proprietary formulation has demonstrated blood sugar-lowering effects of resveratrol in type 2 diabetes mellitus. As with many polyphenols, resveratrol is reasonably well absorbed but has low bioavailability. It is metabolized by hydroxylation, glucuronidation, sulfation and hydrogenation. We reviewed the published literature and reports to consolidate information available on the biological activity of resveratrol using electronic databases as well as handpicked articles to summarize the biological effects of resveratrol and its clinical benefits against human diseases.

  3. Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1.

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    Zhang, Nannan; Li, Zhongchi; Xu, Kang; Wang, Yanying; Wang, Zhao

    2016-01-01

    Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction. PMID:27582325

  4. Resveratrol and Omega 3 fatty acid: Its implications in Cardiovascular Diseases

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    Bibhuti B Kakoti

    2015-12-01

    Full Text Available The present review aimed at summarizing the major therapeutic roles of resveratrol and omega-3 fatty acids along with their related pathways. This article reviews some of the key studies involving the health benefits of resveratrol and omega 3 fatty acids. Oxidative stress has been considered as one of the most important pathophysiological factor associated with various cardiovascular disease conditions. Resveratrol with the potent antioxidant and free radical scavenging properties has been proven to be a significantly protective compound in restoring the normal cardiac health. A plethora of research also demonstrated the reduction of the risk of coronary heart disease, hypertension and stroke, and their complications by omega-3 fatty acids derived from fish and fish oils. This review describes the potential cardioprotective role of resveratrol and omega 3 fatty acids in ameliorating the endoplasmic reticulum (ER stress.

  5. Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice

    International Nuclear Information System (INIS)

    Nonmelanoma skin cancer is the most common cancer among humans and solar UV radiation, particularly its UVB component (290-320 nm), is its major cause. One way to reduce the occurrence of the cancer is via the use of substances (often antioxidants) termed 'photochemopreventive agents'. Resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin found in grapes, nuts, fruits, and red wine, is a potent antioxidant with strong anti-inflammatory and antiproliferative properties. This study was designed to examine whether resveratrol possesses the potential to ameliorate the damages caused by short-term UVB exposure to mouse skin. Single topical application of resveratrol (25 μmol/0.2 ml acetone per mouse) to SKH-1 hairless mice was found to result in significant inhibition of UVB (180 mJ/cm2)-mediated increase in bifold skin thickness and skin edema. The resveratrol treatment to mouse skin was also found to result in significant inhibition of UVB-mediated induction of cyclooxygenase and ornithine decarboxylase (ODC) enzyme activities and protein expression of ODC, which are well-established markers for tumor promotion. We also observed that resveratrol inhibits UVB-mediated increased level of lipid peroxidation, a marker of oxidative stress. Taken together, our results suggest that resveratrol may afford substantial protection against the damages caused by UVB exposure, and these protective effects may be mediated via its antioxidant properties

  6. Resveratrol and obesity: Can resveratrol relieve metabolic disturbances?

    NARCIS (Netherlands)

    Ligt, M. de; Timmers, S.; Schrauwen, P.

    2015-01-01

    There is an increasing need for novel preventive and therapeutic strategies to combat obesity and related metabolic disorders. In this respect, the natural polyphenol resveratrol has attracted significant interest. Animal studies indicate that resveratrol mimics the effects of calorie restriction vi

  7. Protective effects of resveratrol in experimental retinal detachment.

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    Wei Huang

    Full Text Available BACKGROUND: Oxidative stress is one of the major factors that trigger photoreceptor apoptosis. To investigate whether resveratrol, a potent antioxidant and small molecule activator of the FoxO pathway, would be neuroprotective against photoreceptor cell death in a rodent model of retinal detachment. METHODS: Retinal detachment was created in adult Brown Norway rats by subretinal injection of sodium hyaluronate. The animals were treated daily with vehicle or resveratrol (20 mg/kg intraperitoneal injection. Photoreceptor death was assessed by counting the number of apoptotic cells with TdT-dUTP terminal nick-end labeling (TUNEL and measurement of the outer nuclear layer (ONL thickness 3 days after RD. Changes in expression of FoxO1a, FoxO3a, and FoxO4 were analyzed by western blot. The activity of caspase 3, caspase 8, caspase 9, spectrin and their cleavage forms were studied. RESULTS: Three days after retinal detachment, caspase 3, caspase 8 and caspase 9 were significantly activated in the detached retina. Spectrin cleavage products at 120 and 145 kDa were also detected. Both caspase and calpain activation are involved in apoptotic photoreceptor cell death in detached retinas. Treatment with resveratrol increases FoxO1a, FoxO3a, and FoxO4 protein expression in detached retinas only. Resveratrol treatment decreases activation of intrinsic and extrinsic caspase apoptotic pathways triggered by RD. The number of TUNEL-positive cells decreases from 1301±51 cells/mm(2 in control groups to 430±35 cells/mm(2 in treatment groups (p<0.05. Resveratrol treatment also demonstrates 59% less ONL thickness loss compared to controls. CONCLUSIONS: Resveratrol treatment up-regulates the FoxO family and blocks Caspase3, 8, and 9 activation. Resveratrol has the potential to be used as a novel therapeutic agent for preventing vision loss in diseases characterized by photoreceptor detachment.

  8. Assessment in vitro of radioprotective efficacy of curcumin and resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Sebastia, Natividad, E-mail: natividad.sebastia@uv.es [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain); Montoro, Alegria [Servicio de Proteccion Radiologica, Hospital Universitario La Fe, 46009, Valencia (Spain); Montoro, Amparo [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain); Almonacid, Miguel; Villaescusa, Juan Ignacio [Servicio de Proteccion Radiologica, Hospital Universitario La Fe, 46009, Valencia (Spain); Cervera, Jose; Such, Esperanza; Silla, Ma Angeles [Servicio de Hematologia, Hospital Universitario La Fe, 46009, Valencia (Spain); Soriano, Jose Miguel [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain)

    2011-09-15

    Many natural substances have been studied in recent past to be used as radioprotectors to mitigate ionizing radiation-induced damage in mammalian systems due to its effectiveness given both pre- and post-irradiation and for long time with out drug-related toxicity. Curcumin and trans-resveratrol are both natural occurring polyphenols, obtained from the root of Curcuma longa and from grapes and other berries, respectively. These compounds have shown antioxidant, anti-inflammatory, immunostimulant and anti-carcinogenic properties. Our aim was to evaluate the radioprotective efficacy, in vitro, of curcumin and trans-resveratrol separately against radiation-induced chromosomal aberrations. The study was carried out by the pre-treatment of human blood lymphocytes at concentrations from 0 to 500 {mu}g mL{sup -1} and from 0 to 50 {mu}g mL{sup -1} for curcumin and trans-resveratrol, respectively. The results showed that all concentrations tested reduced radiation-induced chromosomal damage. Maximum damage protection was observed at the concentration of 5 {mu}g mL{sup -1} for curcumin and 0.5 {mu}g mL{sup -1} for trans-resveratrol. Thus, our results show that curcumin and trans-resveratrol pre-treatment significantly protect normal lymphocytes against {gamma}-radiation-induced cellular damage.

  9. Assessment in vitro of radioprotective efficacy of curcumin and resveratrol

    International Nuclear Information System (INIS)

    Many natural substances have been studied in recent past to be used as radioprotectors to mitigate ionizing radiation-induced damage in mammalian systems due to its effectiveness given both pre- and post-irradiation and for long time with out drug-related toxicity. Curcumin and trans-resveratrol are both natural occurring polyphenols, obtained from the root of Curcuma longa and from grapes and other berries, respectively. These compounds have shown antioxidant, anti-inflammatory, immunostimulant and anti-carcinogenic properties. Our aim was to evaluate the radioprotective efficacy, in vitro, of curcumin and trans-resveratrol separately against radiation-induced chromosomal aberrations. The study was carried out by the pre-treatment of human blood lymphocytes at concentrations from 0 to 500 μg mL-1 and from 0 to 50 μg mL-1 for curcumin and trans-resveratrol, respectively. The results showed that all concentrations tested reduced radiation-induced chromosomal damage. Maximum damage protection was observed at the concentration of 5 μg mL-1 for curcumin and 0.5 μg mL-1 for trans-resveratrol. Thus, our results show that curcumin and trans-resveratrol pre-treatment significantly protect normal lymphocytes against γ-radiation-induced cellular damage.

  10. The Phytoalexin Resveratrol Ameliorates Ochratoxin A Toxicity in Human Embryonic Kidney (HEK293) Cells.

    Science.gov (United States)

    Raghubeer, Shanel; Nagiah, Savania; Phulukdaree, Alisa; Chuturgoon, Anil

    2015-12-01

    Ochratoxin A (OTA) is a nephrotoxic mycotoxin produced by Aspergillus and Penicillium fungi. It contaminates human and animal food products, and chronic exposure is associated with renal fibrosis in humans (Balkan endemic nephropathy). Resveratrol, a phytoalexin, possesses anti-cancer and antioxidant properties. We investigated the mechanism of cellular oxidative stress induced by OTA, and the effect of resveratrol in human embryonic kidney (HEK293) cells over 24 and 48 h. Cells were exposed to OTA [IC50 = 1.5 μM (24 h) and 9.4 μM (48 h) determined using MTT assay] and 25 μM resveratrol. Glutathione was quantified by luminometry and gene expression of Nrf2 and OGG1 was determined by qPCR. Protein expression of Nrf2, LonP1, SIRT3, and pSIRT1 was assessed by Western blot, DNA damage (comet assay), and intracellular reactive oxygen species (flow cytometry). At 24 h, resveratrol increased mRNA expression of the DNA repair enzyme, OGG1 (P < 0.05), whereas OTA and OTA+resveratrol significantly decreased OGG1 expression (P < 0.05). OGG1 expression increased during 48-h exposure to resveratrol and OTA+resveratrol (P < 0.05). Comet tail lengths doubled in 48-h OTA-treated cells, whereas at both time periods, OTA+resveratrol yielded shorter comet tails (P < 0.0001). During 24- and 48-h exposure, OTA, resveratrol, and OTA+resveratrol significantly decreased mRNA expression of Nrf2 (P < 0.05). Luminometry analysis of GSH revealed an increase by OTA+resveratrol for 24 and 48 h (P < 0.05 and P < 0.001, respectively). Western blot analysis showed decreased Nrf2 protein expression during 24-h exposure, but increased Nrf2 expression during 48 h. LonP1 protein expression increased during 24-h exposure to OTA (P < 0.05) and OTA+resveratrol (P < 0.0011) and during 48-h exposure to resveratrol (P < 0.0005).

  11. Resveratrol and Ophthalmic Diseases

    Directory of Open Access Journals (Sweden)

    Khaled K. Abu-Amero

    2016-04-01

    Full Text Available Resveratrol, a naturally occurring plant polyphenol found in grapes, is the principal biologically active component in red wine. Clinical studies have shown that resveratrol due to its potent anti-oxidant and anti-inflammatory properties are cardio-protective, chemotherapeutic, neuroprotective, and display anti-aging effects. Oxidative stress and inflammation play a critical role in the initiation and progression of age-related ocular diseases (glaucoma, cataract, diabetic retinopathy and macular degeneration that lead to progressive loss of vision and blindness. In vitro and in vivo (animal model experimental studies performed so far have provided evidence for the biological effects of resveratrol on numerous pathways including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, pro-survival or angiogenesis that are implicated in the pathogenesis of these age-related ocular disorders. In this review, we provide a brief overview of current scientific literature on resveratrol, its plausible mechanism(s of action, its potential use and current limitations as a nutritional therapeutic intervention in the eye and its related disorders.

  12. Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress.

    Science.gov (United States)

    Duan, Guo-Li; Wang, Chang-Nan; Liu, Yu-Jian; Yu, Qing; Tang, Xiao-Lu; Ni, Xin; Zhu, Xiao-Yan

    2016-06-30

    We have recently demonstrated that endotoxin causes oxidative stress and overproduction of nitric oxide in adrenal glands, thereby leading to adrenocortical insufficiency. The aim of this study is to investigate the effects of resveratrol, a natural plant polyphenol with anti-oxidant and anti-nitrative properties, on endotoxemia-associated adrenocortical insufficiency. Resveratrol was administered immediately before injection of lipopolysaccharide (LPS). Twenty four hours later, the adrenocorticotropic hormone (ACTH) stimulation tests was been performed to measure the plasma corticosterone level and the adrenal gland tissues were collected for histopathologic examination, and determination of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) and peroxynitrite production. Treatment with resveratrol significantly inhibited endotoxemia-induced iNOS expression, NO production, and peroxynitrite formation and also attenuated LPS-induced oxidative stress in the adrenal gland, as evidenced by the decrease of pro-oxidant biomarker (MDA), and the increases of anti-oxidant biomarkers (T-AOC, CAT and SOD activity). H&E staining demonstrated that administration of LPS resulted in increased into the adrenal gland. H&E-stained sections of adrenal glands demonstrated signs of leukocyte infiltration and hemorrhage during endotoxemia, which were significantly improved by resveratrol treatment. In addition, resveratrol reversed the LPS-induced downregulation of ACTH receptor and silent information regulator 1 (SIRT1) in adrenal gland, as well as adrenocortical hyporesponsiveness to ACTH. Resveratrol exerts protective effects against endotoxemia-associated adrenocortical insufficiency by suppressing oxidative/nitrative stress. These findings support the potential for resveratrol as a possible pharmacological agent to improve adrenocortical

  13. Therapy with resveratrol attenuates obesity-associated allergic airway inflammation in mice.

    Science.gov (United States)

    André, Diana Majolli; Calixto, Marina Ciarallo; Sollon, Carolina; Alexandre, Eduardo Costa; Leiria, Luiz O; Tobar, Natalia; Anhê, Gabriel Forato; Antunes, Edson

    2016-09-01

    Obesity and insulin resistance have been associated with deterioration in asthma outcomes. High oxidative stress and deficient activation of AMP-activated protein kinase (AMPK) have emerged as important regulators linking insulin resistance and inflammation. This study aimed to evaluate the effects of resveratrol on obesity-associated allergic pulmonary inflammation. Male C57/Bl6 mice fed with high-fat diet to induce obesity (obese group) or standard-chow diet (lean group) were treated or not with resveratrol (100mg/kg/day, two weeks). Mice were sensitized and challenged with ovalbumin (OVA). At 48h thereafter, bronchoalveolar lavage fluid was performed, and lungs collected for morphological studies and Western blot analysis. Treatment of obese mice with resveratrol significantly reduced hyperglycemia and insulin resistance, as well as the body measures (body mass, fat mass, % fat, and body area). OVA-challenge promoted a higher increase in pulmonary eosinophil infiltration in obese compared with lean mice, which was nearly abrogated by resveratrol treatment. Resveratrol markedly increased the phosphorylated AMPK expression in lung tissues of obese compared with lean mice. Resveratrol reduced the p47phox expression and reactive-oxygen species (ROS) production, and elevated the superoxide dismutase (SOD) levels in lung tissues of obese mice. The increased pulmonary levels of TNF-α and inducible nitric oxide synthase (iNOS) in obese mice were also normalized after resveratrol treatment. In lean mice, resveratrol failed to affect the levels of fasting glucose, p47phox, ROS levels, TNF-α, iNOS and phosphorylated AMPK. Resveratrol exhibits protective effects in obesity-associated lung inflammation that is accompanied by local AMPK activation and antioxidant property. PMID:27344038

  14. Enzymatic Biosynthesis of Novel Resveratrol Glucoside and Glycoside Derivatives

    OpenAIRE

    Pandey, Ramesh Prasad; Parajuli, Prakash; Shin, Ju Yong; Lee, Jisun; Lee, Seul; Hong, Young-Soo; Park, Yong Il; Kim, Joong Su; Sohng, Jae Kyung

    2014-01-01

    A UDP glucosyltransferase from Bacillus licheniformis was overexpressed, purified, and incubated with nucleotide diphosphate (NDP) d- and l-sugars to produce glucose, galactose, 2-deoxyglucose, viosamine, rhamnose, and fucose sugar-conjugated resveratrol glycosides. Significantly higher (90%) bioconversion of resveratrol was achieved with α-d-glucose as the sugar donor to produce four different glucosides of resveratrol: resveratrol 3-O-β-d-glucoside, resveratrol 4′-O-β-d-glucoside, resveratr...

  15. Resveratrol attenuates acute kidney injury by inhibiting death receptor‑mediated apoptotic pathways in a cisplatin‑induced rat model.

    Science.gov (United States)

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-10-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti‑inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin‑induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor‑α (TNF‑α), caspase‑8 and Bcl‑2 associated protein X apoptosis regulator (Bax), and decreased expression of anti‑apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl‑2). Administration of resveratrol significantly reversed the cisplatin‑induced alteration in these apoptosis‑associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin‑induced acute kidney injury through inactivation of the death receptor‑mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  16. Resveratrol immobilization and release in polymeric hydrogels

    International Nuclear Information System (INIS)

    Resveratrol (3, 4', 5-trihydroxystilbene) is a polyphenolic produced by a wide variety of plants in response to injury and found predominantly in grape skins. This active ingredient has been shown to possess benefits for the health, such as the antioxidant capacity which is related to the prevention of several types of cancer and skin aging. However, the oral bioavailability of resveratrol is poor and makes its topical application interesting. The purpose of this study was to immobilize resveratrol in polymeric hydrogels to obtain a release device for topical use. The polymeric matrices composed of poli(N-vinyl-2-pyrrolidone) (PVP), poly(ethyleneglycol) (PEG) and agar or PVP and glycerol irradiated at 20 kGy dose were physical-chemically characterized by gel fraction and swelling tests and its preliminary biocompatibility by in vitro test of cytotoxicity using the technique of neutral red uptake. Due to low solubility of resveratrol in water, the addition of 2% ethanol to the matrices was verified. All matrices showed a high crosslinking degree, capacity of swelling and the preliminary cytotoxicity test showed nontoxicity effect. The devices were obtained by resveratrol immobilization in polymeric matrices, carried out in a one-or-two-steps process, that is, before or after irradiation, respectively. The one step resveratrol devices were characterized by gel fraction, swelling tests and preliminary biocompatibility, and their properties were maintained even after the resveratrol incorporation. The devices containing 0,05% of resveratrol obtained by one-step process and 0,1% of resveratrol obtained by two-steps process were submitted to the release test during 24 h. Resveratrol quantification was done by high performance liquid chromatography (HPLC). The results obtained in the kinetics of release showed that only the devices obtained by two-step process release the resveratrol, which demonstrate antioxidant capacity after the release. (author)

  17. Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet.

    Science.gov (United States)

    Pan, Qing-Rong; Ren, Yan-Long; Zhu, Jia-Jia; Hu, Yan-Jin; Zheng, Jin-Su; Fan, Hui; Xu, Yuan; Wang, Guang; Liu, Wen-Xian

    2014-07-14

    Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

  18. Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Qing-Rong Pan

    2014-07-01

    Full Text Available Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol. Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB and superoxide dismutase (SOD, the content of malondialdehyde (MDA, and the protein levels of tumor necrosis factor (TNF-α, monocyte chemotactic protein-1 (MCP-1, nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

  19. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol

    Science.gov (United States)

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  20. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol.

    Science.gov (United States)

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  1. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups often: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfu-sion for 45 min; (4) I-R/Resveratrol group: rats pretreat-ed with resveratrol (10 μmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratrol-treated livers.CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusion-related liver injury.

  2. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

    Science.gov (United States)

    Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed As

    2016-01-01

    Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities

  3. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

    Science.gov (United States)

    Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed As

    2016-01-01

    Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities

  4. Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death.

    Science.gov (United States)

    Amri, Ahmed; Le Clanche, Solenn; Thérond, Patrice; Bonnefont-Rousselot, Dominique; Borderie, Didier; Lai-Kuen, René; Chaumeil, Jean-Claude; Sfar, Souad; Charrueau, Christine

    2014-04-01

    The aim of the present study was to develop and characterize a resveratrol self-emulsifying drug delivery system (Res-SEDDS), and to compare the uptake of resveratrol by bovine aortic endothelial cells (BAECs), and the protection of these cells against hydrogen peroxide-mediated cell death, versus a control resveratrol ethanolic solution. Three Res-SEDDSs were prepared and evaluated. The in vitro self-emulsification properties of these formulations, the droplet size and the zeta potential of the nanoemulsions formed on adding them to water under mild agitation conditions were studied, together with their toxicity on BAECs. An optimal atoxic formulation (20% Miglyol® 812, 70% Montanox® 80, 10% ethanol 96% v/v) was selected and further studied. Pre-incubation of BAECs for 180 min with 25 μM resveratrol in the nanoemulsion obtained from the selected SEDDS significantly increased the membrane and intracellular concentrations of resveratrol (for example, 0.076±0.015 vs. ethanolic solution 0.041±0.016 nmol/mg of protein after 60 min incubation, p<0.05). Resveratrol intracellular localization was confirmed by fluorescence confocal microscopy. Resveratrol nanoemulsion significantly improved the endothelial cell protection from H2O2-induced injury (750, 1000 and 1500 μM H2O2) in comparison with incubation with the control resveratrol ethanolic solution (for example, 55±6% vs. 38±5% viability after 1500 μM H2O2 challenge, p<0.05). In conclusion, formulation of resveratrol as a SEDDS significantly improved its cellular uptake and potentiated its antioxidant properties on BAECs. PMID:24184672

  5. Nanoscale Delivery of Resveratrol towards Enhancement of Supplements and Nutraceuticals

    Science.gov (United States)

    Neves, Ana Rute; Martins, Susana; Segundo, Marcela A.; Reis, Salette

    2016-01-01

    Resveratrol was investigated in terms of its stability, biocompatibility and intestinal permeability across Caco-2 cell monolayers in its free form or encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs and NLCs presented a mean diameter between 160 and 190 nm, high negative zeta potential of −30 mV and resveratrol entrapment efficiency of 80%, suggesting they are suitable for resveratrol oral delivery. Nanoencapsulation effectively protected resveratrol from photodegradation, and MTT assays demonstrated that neither resveratrol nor lipid nanoparticles adversely affected cell viability and integrity of Caco-2 cell monolayers. The in vitro intestinal permeability of resveratrol was significantly increased by NLCs, and SLNs did not impair the absorption of resveratrol. Resveratrol oral absorption can be enhanced during meals, since the intestinal permeability was increased in the presence of fed-state intestinal juices. SLNs and NLCs constitute carrier systems for resveratrol oral administration, for further use as supplements or nutraceuticals. PMID:26950147

  6. 桑白皮中白藜芦醇、氧化白藜芦醇和桑皮苷的抗氧化活性%Antioxidant Activities of Resveratrol,Oxyresveratrol,Esveratrol,Mulberroside A from Cortex mori

    Institute of Scientific and Technical Information of China (English)

    王元成; 伍春; 陈虎; 郑颖; 徐立; 黄先智

    2011-01-01

    二苯乙烯类化合物具有很好的抗氧化和抑制酪氨酸酶的活性,以熊果苷、VC、VE为参照,对桑白皮中的3种二苯乙烯类化合物(氧化白藜芦醇、白藜芦醇、桑皮苷)的抗氧化和清除自由基的生物活性进行比较研究。结果表明:还原力强弱:VC〉白藜芦醇〉氧化白藜芦醇〉VE〉熊果苷〉桑皮苷;清除DPPH自由基能力:VC〉VE〉氧化白藜芦醇〉白藜芦醇〉桑皮苷〉熊果苷;清除ABTS+.能力:白藜芦醇〉氧化白藜芦醇〉熊果苷〉桑皮苷〉VC〉VE。%Stilbene compounds can protect foods from oxidation and inhibit tyrosinase activity.Using arbutin,vitamin C(VC) and vitamin E(VE) as the reference substances,the antioxidant activities and radical scavenging capacities of 3 kinds of stilbene compounds such as resveratrol,oxyresveratrol and mulberroside A from Cortex mori were investigated.The results showed that the six investigated antioxidant substances ranked in the following order: VC resveratrol oxyresveratrol VE arbutin mulberroside A in terms of their reducing power,VC VE oxyresveratrol resveratrol arbutin mulberroside A in terms of their DPPH radical scavenging capacity,and resveratrol oxyresveratrol arbutin mulberroside A VC VE in terms of their ABTS+· scavenging capacity.These results will promote their application in food additives.

  7. Study of radioprotective effect of the resveratrol

    International Nuclear Information System (INIS)

    Resveratrol (3,4,5 trihydroxystilbene), a phenolic phytoalexin occurring naturally in a wide variety of plants, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is present at high levels and is considered one of the highest antioxidant constituents. This high capacity to scavenge the free radicals generated by several biologic processes by resveratrol can provide a prevention of human cardiovascular diseases and several types of cancer. The main objective of this study was to determine the in vitro radioprotective effect of resveratrol in cell culture with the aid of the tests of cytotoxicity of resveratrol (IC50%) and lethal dose 50% of gamma radiation (LD50). Studies of the level of resveratrol toxicity, found by cytotoxicity test performed by neutral red uptake assay, and lethal dose 50% (LD50) of gamma radiation from source of Cobalt-60 (Co-60) was performed in cell culture NCTC Clone 929 from ATCC. The IC50% of resveratrol was about 50 M/L. The DL50 of gamma radiation showed a value of about 354 Gy. On the basis of these biological results, it was performed studies of radioprotective effect of resveratrol on the same experimental conditions, verifying that the resveratrol in concentrations between 12.5 M/L and 25 M/L showed a more pronounced radioprotective effect. (author)

  8. AN UPDATE ON PHARMACOLOGICAL PROPERTIES OF RESVERATROL

    Directory of Open Access Journals (Sweden)

    Agnihotri Gaytri

    2012-08-01

    Full Text Available Resveratrol, red wine mainly present in grapes acts as a natural phytoalexin and phytoestrogen. It has potent antioxidant activity and then has been implicated in the management of various cardiovascular and inflammatory disorders. Further, it has been also documented to be successful in the reduction of ischemic reperfusion [I/R] injury. It has been found to possess immunosuppressive property and is used as anti-cancer and ameliorates the endothelial functions. Still, no evidence is availible that suggest signaling pathway mechanism associated with resveratrol. Thus, the present review deals with the update of various signaling pathway and therapeutic implications of resveratrol in the management of various disorders.

  9. Resveratrol immobilization and release in polymeric hydrogels; Incorporacao e liberacao de resveratrol em hidrogeis polimericos

    Energy Technology Data Exchange (ETDEWEB)

    Momesso, Roberta Grazzielli Ramos Alves Passarelli

    2010-07-01

    Resveratrol (3, 4', 5-trihydroxystilbene) is a polyphenolic produced by a wide variety of plants in response to injury and found predominantly in grape skins. This active ingredient has been shown to possess benefits for the health, such as the antioxidant capacity which is related to the prevention of several types of cancer and skin aging. However, the oral bioavailability of resveratrol is poor and makes its topical application interesting. The purpose of this study was to immobilize resveratrol in polymeric hydrogels to obtain a release device for topical use. The polymeric matrices composed of poli(N-vinyl-2-pyrrolidone) (PVP), poly(ethyleneglycol) (PEG) and agar or PVP and glycerol irradiated at 20 kGy dose were physical-chemically characterized by gel fraction and swelling tests and its preliminary biocompatibility by in vitro test of cytotoxicity using the technique of neutral red uptake. Due to low solubility of resveratrol in water, the addition of 2% ethanol to the matrices was verified. All matrices showed a high crosslinking degree, capacity of swelling and the preliminary cytotoxicity test showed nontoxicity effect. The devices were obtained by resveratrol immobilization in polymeric matrices, carried out in a one-or-two-steps process, that is, before or after irradiation, respectively. The one step resveratrol devices were characterized by gel fraction, swelling tests and preliminary biocompatibility, and their properties were maintained even after the resveratrol incorporation. The devices containing 0,05% of resveratrol obtained by one-step process and 0,1% of resveratrol obtained by two-steps process were submitted to the release test during 24 h. Resveratrol quantification was done by high performance liquid chromatography (HPLC). The results obtained in the kinetics of release showed that only the devices obtained by two-step process release the resveratrol, which demonstrate antioxidant capacity after the release. (author)

  10. Wirkmechanismen der Resveratrol-Behandlung in Fibroblasten

    OpenAIRE

    Wowro, S.

    2012-01-01

    Resveratrol, a well-known phytoalxin, is present in numerous plants, and produced as protection against environmental risks. In mammals Resveratrol exhibits diverse effects, including anti-inflammatory and anti-oxidative properties as well as a broad range of health benefits by activating mitochondrial biogenesis. Most studies have shown the impact in cardiovascular diseases, cancer and metabolic dysfunctions, but little is known about the influence on the skin. Many skin diseases are associa...

  11. Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol.

    Science.gov (United States)

    Banerjee, Bhaswati; Chakraborty, Supriya; Ghosh, Debidas; Raha, Sanghamitra; Sen, Parimal C; Jana, Kuladip

    2016-01-01

    Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ

  12. Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Ozkan ATES; Suleyman CAYLI; Eyup ALTINOZ; Iclal CURSES; Neslihan YUCEL; Ayhan KOCAK; Saim YOLOGLU; Yusuf TURKOZ

    2006-01-01

    Aim: To investigate the neuroprotective effect of resveratrol in an experimental spinal cord injury (SCI) model in rats. Methods: Male Wistar albino rats weighing 200-250 g were randomized into six groups. Weight-drop trauma was performed for SCI. Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed by SCI. Groups 3, 4, 5, and 6 underwent laminectomy followed by SCI and received resveratrol (100 mg/kg), methylprednisolone (MP) (30 mg/kg), resveratrol (100 mg/kg) plus MP (30 mg/kg), and ethanol (2%), respectively. The rats were divided into two subgroups for biochemical analysis (killed at 24 h after surgery) and for neurobehavioral and histopathological evaluation (killed at 6 weeks after surgery). Posttraumatic neurological recovery after surgery was recorded weekly. Results: Groups 3 and 5 revealed significantly lower malondialdehyde, nitric oxide, xanthine oxidase, and higher glutathione levels than group 4 (P<0.05). Neurological recovery rates were significantly better in groups 3 and 5 than group 4 (P<0.05). When spinal trauma size ratios were compared, there was no significant difference between treatment groups. Conclusion: Resveratrol treatment revealed better biochemical recovery in the acute stage of trauma than MP treatment. Although resveratrol and combined treatment revealed better neurobehavioral recovery than MP treatment; resveratrol, MP, and combined treatment modalities improved histopathological recovery at the same level in the final stage of the experiment. Future studies involving different doses of resveratrol and different doses combinations with MP could promise better results as each drug has a different anti-oxidative mechanism of action.

  13. The effects of resveratrol on rat behaviour in the forced swim test

    Directory of Open Access Journals (Sweden)

    Samardžić Janko

    2013-01-01

    Full Text Available Introduction. The trans-isomer of resveratrol is the active ingredient of Poligonum cuspidatum, known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders. It is also found abundantly in the skin of red grapes and red wine. Previous studies have suggested that trans-resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, as well as neuroprotective properties and procognitive effects. Objective. The goal of the present study was to examine the influence of trans-resveratrol on behavior in rats and its antidepressant properties. Methods. Male Wistar rats were treated intraperitoneally (i.p. with the increasing doses of trans-resveratrol (5, 10 and 20 mg/kg or vehicle (dimethyl sulfoxide - DMSO, 30 minutes before testing of the spontaneous locomotor activity or forced swimming. For the experiments, the behavior of the animals was recorded by a digital camera, and the data were analyzed by one-way ANOVA, followed by Tukey post-hoc test. Results. Testing of spontaneous locomotor activity, after the application of vehicle or increasing doses of trans-resveratrol, showed no statistically significant difference between groups (p>0.05. In the forced swim test, one-way ANOVA indicated statistically significant effects of trans-resveratrol (p0.05. Conclusion. The results from our study suggest that trans-resveratrol produces significant effects in the central nervous system. After single application, it has acute antidepressant effects, but without influence on locomotor activity. [Projekat Ministarstva nauke Republike Srbije, br. TR31020 i br. 175076

  14. Resveratrol ameliorates muscular pathology in the dystrophic mdx mouse, a model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Hori, Yusuke S; Kuno, Atsushi; Hosoda, Ryusuke; Tanno, Masaya; Miura, Tetsuji; Shimamoto, Kazuaki; Horio, Yoshiyuki

    2011-09-01

    Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. We previously showed that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and activator of the NAD(+)-dependent protein deacetylase SIRT1, delays the progression of heart failure and prolongs the lifespan of δ-sarcoglycan-deficient hamsters. Because a defect of dystroglycan complex causes muscular dystrophies, and δ-sarcoglycan is a component of this complex, we hypothesized that resveratrol might be a new therapeutic tool for muscular dystrophies. Here, we examined resveratrol's effect in mdx mice, an animal model of Duchenne muscular dystrophy. mdx mice that received resveratrol in the diet for 32 weeks (4 g/kg diet) showed significantly less muscle mass loss and nonmuscle interstitial tissue in the biceps femoris compared with mdx mice fed a control diet. In the muscles of these mice, resveratrol significantly decreased oxidative damage shown by the immunostaining of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine and suppressed the up-regulation of NADPH oxidase subunits Nox4, Duox1, and p47(phox). Resveratrol also reduced the number of α-smooth muscle actin (α-SMA)(+) myofibroblast cells and endomysial fibrosis in the biceps femoris, although the infiltration of CD45(+) inflammatory cells and increase in transforming growth factor-β1 (TGF-β1) were still observed. In C2C12 myoblast cells, resveratrol pretreatment suppressed the TGF-β1-induced increase in reactive oxygen species, fibronectin production, and expression of α-SMA, and SIRT1 knockdown blocked these inhibitory effects. SIRT1 small interfering RNA also increased the expression of Nox4, p47(phox), and α-SMA in C2C12 cells. Taken together, these findings indicate that SIRT1 activation may be a useful strategy for treating muscular dystrophies. PMID:21652783

  15. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jia-hua; CHENG Hai-yan; YU Ze-qian; HE Dao-wei; PAN Zheng; YANG De-tong

    2011-01-01

    Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years.Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer.The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells,capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.Conclusion Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

  16. Peroxynitrite Scavenging Activities of Resveratrol and Piceid

    Institute of Scientific and Technical Information of China (English)

    ZHAO Guang-rong; TIAN Li-li; MA Qiong; WANG Chang-song; QIAO Bin; ZHANG Jun-gang; JI Xiang-wu

    2012-01-01

    In vitro antioxidant activities of resveratrol and piceid against peroxynitrite(ONOO-) were examined by the inhibition of 3-nitrotyrosine formation.Trolox was used as a positive control.Resveratrol and piceid exhibited high ONOO--scavenging activities in a concentration dependent manner.The antioxidant activities(the concentration of test compound required to yield a 50% inhibition of tyrosine nitration,IC50) of resveratrol and piceid against ONOO-were (48.34±0.97) and (74.69±1.49) μmol/L,respectively.Compared with that of trolox[(105.40±1.16)μmol/L],their scavenging activities were 2.2-and 1.5-fold higher for resveratrol and piceid.Formation of nitroresveratrol as shown by UV-Vis spectroscopy and liquid chromatography-tandom mass spectrometry(LC-MS/MS) analysis indicates that resveratrol could directly scavenge ONOO-via nitration reaction.Our results demonstrate that foods and medicinal herbs with resveratrol and piceid as stronger ONOO-scavengers are valuable ingredients and have healthy application in preventing humans from peroxynitrite-mediated oxidative damage by scavenging peroxynitrite efficiently.

  17. Study of radioprotective effect of the resveratrol;Estudo do efeito radioprotetor do resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Carolina dos Santos

    2009-07-01

    Resveratrol (3,4,5 trihydroxystilbene), a phenolic phytoalexin occurring naturally in a wide variety of plants, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is present at high levels and is considered one of the highest antioxidant constituents. This high capacity to scavenge the free radicals generated by several biologic processes by resveratrol can provide a prevention of human cardiovascular diseases and several types of cancer. The main objective of this study was to determine the in vitro radioprotective effect of resveratrol in cell culture with the aid of the tests of cytotoxicity of resveratrol (IC50%) and lethal dose 50% of gamma radiation (LD50). Studies of the level of resveratrol toxicity, found by cytotoxicity test performed by neutral red uptake assay, and lethal dose 50% (LD50) of gamma radiation from source of Cobalt-60 (Co-60) was performed in cell culture NCTC Clone 929 from ATCC. The IC50% of resveratrol was about 50 M/L. The DL50 of gamma radiation showed a value of about 354 Gy. On the basis of these biological results, it was performed studies of radioprotective effect of resveratrol on the same experimental conditions, verifying that the resveratrol in concentrations between 12.5 M/L and 25 M/L showed a more pronounced radioprotective effect. (author)

  18. Triple antioxidant SNEDDS formulation with enhanced oral bioavailability

    DEFF Research Database (Denmark)

    Tripathi, Shailja; Kushwah, Varun; Thanki, Kaushik;

    2016-01-01

    .3, respectively. DPPH scavenging assay showed comparable antioxidant activity of antioxidant loaded SNEDDS to free antioxidants combination. Furthermore, coumarin-6 loaded SNEDDS formulation showed rapid internalization within 1h of incubation by Caco-2 cells. Moreover, the pharmacokinetic studies in rats......The present study aimed to develop quercetin, resveratrol and genistein loaded self-nanoemulsifying drug delivery system (SNEDDS) by QbD approach in order to improve their oral bioavailability and antioxidant potential. The size and PDI of the optimized formulation were found to be ... for the optimized formulation and free antioxidant suspension were performed. SNEDDS have significantly increased the Cmax and area under curve (AUC) of all three antioxidants. The SNEDDS demonstrated ~4.27 fold enhancement in oral bioavailability of quercetin, ~1.5 fold in case of resveratrol and ~2.8 fold in case...

  19. Stability evaluation of resveratrol submitted to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Momesso, Roberta G.R.A.P.; Silva, Mariana L. da; Spencer, Patrick J.; Sousa, Jose M. de; Rogero, Jose R.; Rogero, Sizue O.; Lugao, Ademar B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: robertapassarelli@yahoo.com.br

    2009-07-01

    The polyphenol trans-resveratrol (trans-3, 4',5-trihydroxystilbene) is a natural phytoalexin, reported to exert different biological activities, such as antioxidant properties. In the attempt to make possible the topic administration of resveratrol it will be immobilized in a hydrogel matrix obtained by gamma radiation crosslinking process which can cause undesirable hydrolysis reactions in the active compound. The aim of this work was to verify the aqueous/ethanol resveratrol solution stability and antioxidant activity after irradiation at 20 kGy. The integrity and stability were compared with nature one by High Performance Liquid Chromatography (HPLC) technique. The antioxidant activity was determined by the free radical scavenging method, using 2,2-Diphenyl-1-picrylhydrazyl (DPPH.) as free radical. The results demonstrated the decomposition of resveratrol and reduction of antioxidant capacity after irradiation at 20 kGy dose. (author)

  20. Stability evaluation of resveratrol submitted to ionizing radiation

    International Nuclear Information System (INIS)

    The polyphenol trans-resveratrol (trans-3, 4',5-trihydroxystilbene) is a natural phytoalexin, reported to exert different biological activities, such as antioxidant properties. In the attempt to make possible the topic administration of resveratrol it will be immobilized in a hydrogel matrix obtained by gamma radiation crosslinking process which can cause undesirable hydrolysis reactions in the active compound. The aim of this work was to verify the aqueous/ethanol resveratrol solution stability and antioxidant activity after irradiation at 20 kGy. The integrity and stability were compared with nature one by High Performance Liquid Chromatography (HPLC) technique. The antioxidant activity was determined by the free radical scavenging method, using 2,2-Diphenyl-1-picrylhydrazyl (DPPH.) as free radical. The results demonstrated the decomposition of resveratrol and reduction of antioxidant capacity after irradiation at 20 kGy dose. (author)

  1. Resveratrol Inhibits Inflammatory Responses via the Mammalian Target of Rapamycin Signaling Pathway in Cultured LPS-Stimulated Microglial Cells

    OpenAIRE

    Zhong, Lian-Mei; Zong, Yi; Sun, Lin; Guo, Jia-Zhi; Zhang, Wei; He, Ying; Song, Rui; Wang, Wen-Min; Xiao, Chun-jie; Lu, Di

    2012-01-01

    Background Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells. Methodolo...

  2. Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol

    Directory of Open Access Journals (Sweden)

    Balata GF

    2016-01-01

    Full Text Available Gehan F Balata,1 Ebtessam A Essa,1,2 Hanan A Shamardl,3,5 Samira H Zaidan,4 Mohammed AS Abourehab1,6 1Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Department of Pharmacology, 4Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 5Department of Pharmacology, Faculty of Medicine, El Fayoom University, 6Department of Pharmaceutics, Faculty of Pharmacy, El-Minia University, Egypt Abstract: Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17–99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of –2.24 to –15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic

  3. Combinational effect of resveratrol and atorvastatin on isoproterenol-induced cardiac hypertrophy in rats

    Directory of Open Access Journals (Sweden)

    Songjukta Chakraborty

    2015-01-01

    Full Text Available Introduction: Resveratrol is a natural polyphenol present mainly in grapes. It has been shown to offer strong cardio protection in animal models due to its ability to correct lipid peroxidation and maintain antioxidants level. Atorvastatin, a HMG-CoA reductase inhibitor, lowers cholesterol level and is commonly prescribed to heart patients. Our aim in this study was to see the combination effect of these two drugs against Isoproterenol-induced cardiac hypertrophy in rats. Materials and Methods: Wister Albino rats were treated with resveratrol (20 mg/kg/day, p.o, atorvastatin (20 mg/kg/day, p.o and in combination (resveratrol [10 mg/kg/day, p.o] + atorvastatin [10 mg/kg/day, p.o] for a period of 25 days and from 15 th till 25 th day Isoproterenol (5 mg/kg/day, s.c was co-administered to rats to induce cardiac hypertrophy. Results: A significant increase in creatine kinase, lactate dehydrogenase, aspartate transaminase and lipid peroxidation with the significant decrease in reduced glutathione, superoxide dismutase and catalase were observed in Isoproterenol treated rats. Resveratrol, atorvastatin and their combination significantly reversed the effect. The histopathological studies and myocardial infarct size evaluation also confirmed the protection. Conclusion: Comparing the data we came to this conclusion that atorvastatin although showed the protection along all the parameters, the extent of protection offered by resveratrol alone and in combination were more effective. Hence, it can be concluded that resveratrol, an herbal nutritional supplement, alone and in combination is better against cardiac hypertrophy.

  4. Resveratrol prevents ammonia toxicity in astroglial cells.

    Directory of Open Access Journals (Sweden)

    Larissa Daniele Bobermin

    Full Text Available Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS. Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS, GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA and extracellular signal-regulated kinase (ERK pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity.

  5. Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.

    Science.gov (United States)

    Liu, Yuanli; Zhou, Jinan; Qu, Yilin; Yang, Xinguang; Shi, Guojing; Wang, Xiuhong; Hong, Yuzhi; Drlica, Karl; Zhao, Xilin

    2016-01-01

    Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical) are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. The possibility has been raised that consumption of antioxidants in food may interfere with the lethal action of antimicrobials. Whether nutritional supplements containing antioxidant activity are also likely to interfere with antimicrobial lethality is unknown. To examine this possibility, resveratrol, a popular antioxidant dietary supplement, was added to cultures of Escherichia coli and Staphylococcus aureus that were then treated with antimicrobial and assayed for bacterial survival and the recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present during human consumption, caused a 2- to 3-fold reduction in killing during a 2-hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders of magnitude. Resveratrol also reduced the increase in reactive oxygen species (ROS) characteristic of treatment with quinolone (oxolinic acid). These data support the general idea that the lethal activity of some antimicrobials involves ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6-fold) the recovery of rifampicin-resistant mutants arising from the action of ciprofloxacin, kanamycin, or daptomycin. This result is consistent with resveratrol reducing ROS to sublethal levels that are still mutagenic, while the absence of resveratrol allows ROS levels to high enough to kill mutagenized cells. Suppression of antimicrobial lethality and promotion of mutant recovery by resveratrol suggests that the antioxidant may contribute to the emergence of resistance to several antimicrobials, especially if new derivatives and/or formulations of resveratrol markedly increase bioavailability. PMID:27045517

  6. Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats.

    Science.gov (United States)

    Abd El-Fattah, Amal Ahmed; Fahim, Atef Tadros; Sadik, Nermin Abdel Hamid; Ali, Bassam Mohamed

    2016-01-01

    The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction. PMID:26361869

  7. Resveratrol supplementation protects against chronic nicotine-induced oxidative damage and organ dysfunction in the rat urogenital system

    Directory of Open Access Journals (Sweden)

    Hale Toklu

    2010-01-01

    Full Text Available The protective effect of resveratrol against nicotine induced oxidative damage on urogenital tissues was evaluated by biochemical, histological and functional studies. Wistar Albino rats were injected with either nicotine hydrogen bitartarate (0.6 mg/kg/day, ip or saline. Resveratrol (10 mg/kg, po was administered along with saline or nicotine injections for 28 days. After decapitation, the urinary bladder, corpus cavernosum and kidney tissues were excised. Corpus cavernosum and bladder tissues were used for in vitro contractility studies, or stored at -80 ºC along with kidney tissue for the measurement of malondialdehyde (MDA, glutathione (GSH, and luminol-lucigenin chemiluminescence (CL levels. Tissue samples were also examined histologically. Chronic nicotine administration caused a significant decrease in GSH levels and increases in MDA levels, and luminol-lucigenin CL in kidney, urinary bladder and corpus cavernosum tissues, suggesting oxidative organ damage, which was also verified histologically. In serum samples increased blood urea nitrogen (BUN, creatinine, proinflammatory cytokines (TNF-α and IL-1β, lactate dehydrogenase (LDH activity, oxidative DNA damage (8-OHdG and decreased antioxidant capacity (AOC due to nicotine administration were reversed with resveratrol. Furthermore, chronic nicotine administration impaired the contractile activity of the bladder and corpus cavernosum strips while resveratrol supplementation to nicotine-treated animals reversed these effects in both tissues. Resveratrol treatment to the nicotine group restored the endogenous GSH levels and decreased oxidative damage parameters in all studied tissues. These data suggest that resveratrol supplementation effectively counteracts the deleterious effect of chronic nicotine administration on bladder, corpus cavernosum and kidney functions and attenuates oxidative damage possibly by its antioxidant effects.

  8. Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Sibel Konyalioglu; Guliz Armagan; Ayfer Yalcin; Cigdem Atalayin; Taner Dagci

    2013-01-01

    Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antioxidant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide + resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage.

  9. Rapid solid-phase extraction and analysis of resveratrol and other polyphenols in red wine.

    Science.gov (United States)

    Hashim, Shima N N S; Schwarz, Lachlan J; Boysen, Reinhard I; Yang, Yuanzhong; Danylec, Basil; Hearn, Milton T W

    2013-10-25

    Red wine has long been credited as a good source of health-beneficial antioxidants, including the bioactive polyphenols catechin, quercetin, and (E)-resveratrol. In this paper, we report the application of reusable molecularly imprinted polymers (MIPs) for the selective and robust solid-phase extraction (SPE) and rapid analysis of (E)-resveratrol (LOD=8.87×10(-3) mg/L, LOQ=2.94×10(-2) mg/L), along with a range of other polyphenols from an Australian Pinot noir red wine. Optimization of the molecularly imprinted solid-phase extraction (MISPE) protocol resulted in the significant enrichment of (E)-resveratrol and several structurally related polyphenols. These secondary metabolites were subsequently identified by RP-HPLC and μLC-ESI ion trap MS/MS methods. The developed MISPE protocol employed low volumes of environmentally benign solvents selected according to the Green Chemistry principles, and resulted in the recovery of 99% of the total (E)-resveratrol present. These results further demonstrate the potential of generic protocols for the analysis of target compound with health beneficial properties within the food and nutraceutical industries using tailor-made MIPs.

  10. Resveratrol Prevents Cardiovascular Complications in the SHR/STZ Rat by Reductions in Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Rebecca K. Vella

    2015-01-01

    Full Text Available The cardioprotective effects of resveratrol are well established in animal models of metabolic disease but are yet to be investigated in a combined model of hypertension and diabetes. This study investigated the ability of resveratrol’s antioxidant and anti-inflammatory effects to prevent cardiovascular complications in the spontaneously hypertensive streptozotocin-induced diabetic rat. Diabetes was induced in eight-week-old male spontaneously hypertensive rats via a single intravenous injection of streptozotocin. Following this, resveratrol was administered orally for an eight-week period until the animals were sixteen weeks of age. Upon completion of the treatment regime assessments of oxidative stress, lipid peroxidation, inflammation, and cardiovascular function were made. Resveratrol administration to hypertensive-diabetic animals did not impact upon blood glucose or haemodynamics but significantly reduced oxidative stress, lipid peroxidation, and inflammatory cytokines. Reductions in systemic levels of oxidative stress and inflammation conferred improvements in vascular reactivity and left ventricular pump function and electrophysiology. This study demonstrates that resveratrol administration to hypertensive diabetic animals can elicit cardioprotective properties via antioxidant and anti-inflammatory effects. The observed preservation of cardiovascular function was independent of changes in blood glucose concentration and haemodynamics, suggesting that oxidative stress and inflammation are key components within the pathological cascade associated with hypertension and diabetes.

  11. [The significance of free radicals and antioxidants due to the load induced by sport activity].

    Science.gov (United States)

    Holecek, V; Liska, J; Racek, J; Rokyta, R

    2004-01-01

    Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable. PMID:15709642

  12. Resveratrol and Health

    DEFF Research Database (Denmark)

    -cancer, anti-inflammatory, blood-sugar-lowering, and other beneficial cardiovascular effects of resveratrol have been reported in experiments with mouse and rat model systems. However, most of these results have yet to be replicated in humans. Resveratrol is found in the skin of red grapes and is a constituent...... of red wine. Resveratrol has also been produced by chemical synthesis or by biotechnological synthesis and is sold as a nutritional supplement derived primarily from Japanese knotweed....

  13. An Electrochemical Study of the Difference in Antioxidant Activity between Resveratrol and Pterostilbene%白藜芦醇与紫檀芪抗氧化活性差异的电化学研究

    Institute of Scientific and Technical Information of China (English)

    余沐洋; 张萌; 高凌峰; 何建波

    2012-01-01

    The oxidation mechanisms of trans-resveratrol and its derivative pterostilbene were studied to better understand the difference in antioxidant activity between the stilbene compounds. The effects of pH and accumulation time were examined by cyclic voltammetry, and the formation of oxidation products was in situ by thin layer UV-Vis spectroelectrochemistry. It was observed that adsorptive accumulation of pterostilbene on the oleaginous surface of the carbon paste working electrode was much stronger than that of resveratrol. The initial oxidation of both the stilbenes occurred at the p-hydroxyl group via one electron one proton transfer, forming phenoxy free radicals. The radical intermediates of pterostilbene might couple immediately to yield dimers at the electrode surface, while those of resveratrol, especially in the alkaline media, had to undergo the oxidative cleavage of the center double bond to produce soluble small molecules. Lipophilicity of pterostilbene superior to resveratrol might be the important reason for its higher antioxidant activity, since lipophilicity increases the adsorptive accumulation as well as accelerates the dimerization of the oxidized radical intermediates.%为揭示白藜芦醇(反式)与其衍生物紫檀芪的抗氧化活性差异的内在原因,对两种物质的氧化机理进行研究。采用循环伏安法考察pH值、富集时间对氧化过程的影响,采用薄层长光程紫外,可见光谱电化学方法原位监测氧化产物的形成。结果表明:紫檀芪在油性碳糊电极表面上的吸附富集作用远强于白藜芦醇;两者的初始氧化都发生在对位羟基上,通过一电子一质了传递步骤生成苯氧自由基中间体;紫檀芪自由基中间体易于耦合迅速转化为二聚体产物,而白藜芦醇自由基在碱性介质中需经历较难进行的中间双键断裂途径,转化为可溶性小分子产物。紫檀芪较强的亲脂性引起的富集作用以及氧化

  14. Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation.

    Directory of Open Access Journals (Sweden)

    Mehtap Kilic Eren

    Full Text Available The natural polyphenolic compound resveratrol (3,4,5-trihydroxy-trans-stilbene has broad spectrum health beneficial activities including antioxidant, anti-inflammatory, anti-aging, anti-cancer, cardioprotective, and neuroprotective effects. Remarkably, resveratrol also induces apoptosis and cellular senescence in primary and cancer cells. Resveratrol's anti-aging effects both in vitro and in vivo attributed to activation of a (NAD-dependent histone deacetylase family member sirtuin-1 (SIRT1 protein. In mammals seven members (SIRT1-7 of sirtuin family have been identified. Among those, SIRT1 is the most extensively studied with perceptive effects on mammalian physiology and suppression of the diseases of aging. Yet no data has specified the role of sirtuins, under conditions where resveratrol treatment induces senescence. Current study was undertaken to investigate the effects of resveratrol in human primary dermal fibroblasts (BJ and to clarify the role of sirtuin family members in particular SIRT1 and SIRT2 that are known to be involved in cellular stress responses and cell cycle, respectively. Here, we show that resveratrol decreases proliferation of BJ cells in a time and dose dependent manner. In addition the increase in senescence associated β-galactosidase (SA-β-gal activity and methylated H3K9-me indicate the induction of premature senescence. A significant increase in phosphorylation of γ-H2AX, a surrogate of DNA double strand breaks, as well as in levels of p53, p21CIP1 and p16INK4A is also detected. Interestingly, at concentrations where resveratrol induced premature senescence we show a significant decrease in SIRT1 and SIRT2 levels by Western Blot and quantitative RT-PCR analysis. Conversely inhibition of SIRT1 and SIRT2 via siRNA or sirtinol treatment also induced senescence in BJ fibroblasts associated with increased SA-β-gal activity, γ-H2AX phosphorylation and p53, p21CIP1 and p16INK4A levels. Interestingly DNA damaging

  15. Resveratrol and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Dominique Bonnefont-Rousselot

    2016-05-01

    Full Text Available The increased incidence of cardiovascular diseases (CVDs has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES, a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS. RES was able to scavenge •OH/O2•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH, an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA. Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…; however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure should compare the results of preclinical studies with those of clinical trials.

  16. 白藜芦醇对高脂饮食大鼠骨骼肌不同线粒体亚群氧化、抗氧化水平和胰岛素敏感性的影响%Effect of resveratrol on the oxidative stress and antioxidant levels of different skeletal muscle mitochondrial subpopulations and insulin sensitivity in rats fed with high-fat diet

    Institute of Scientific and Technical Information of China (English)

    陈璐璐; 张好好; 郑涓; 胡祥; 孔雯; 胡帝; 王素星

    2012-01-01

    Objective To observe the effect of resveratrol on the oxidative stress and antioxidant levels of different mitochondrial subpopulations in the skeletal muscle and insulin sensitivity of rats fed with high-fat diet.Methods Male SD rats,aged 8 weeks,were divided into normal chow (NC) group,high-fat diet(HF) group,high-fat diet plus resveratrol ( HFR ) group.After intervention for 8 weeks,the impacts of resveratrol on oxidative stress levels and antioxidant enzymes activities in subsarcolemmal ( SS ) and intermyofibrillar ( IMF ) mitochondria from skeletal muscle as well as general and skeletal mascle insulin sensitivity were assessed.Results Compared with NC group, insulin sensitivity was significantly reduced while reactive oxygen species (ROS) and malondialdehyde(MDA) levels in SS and IMF mitochondria increased in HF group ( all P<0.01 ).In addition,antioxidant enzyme activities were significantly decreased in SS mitochondrial and increased in IMF mitochondrial ( both P < 0.05 ).Compared with HF group,the insulin sensitivity in HFR group was significantly improved.Moreover,the activities of antioxidant enzymes in SS and IMF mitochondrial were increased,and the oxidative stress levels returned to normal ( P < 0.05 ).Conclusion Resveratrol notably improves the oxidative stress of different skeletal muscle mitochondrial subpopulations and insulin resistance in rats fed with high-fat diet.%目的 观察白藜芦醇对高脂饮食大鼠骨骼肌不同线粒体亚群氧化、抗氧化水平及胰岛素敏感性的影响.方法 8周龄雄性SD大鼠分为普通饮食组(NC组)、高脂饮食组(HF组)及白藜芦醇干预高脂饮食组(HFR组);干预8周后检测各组大鼠骨骼肌肌膜下(SS)及肌纤维间(IMF)线粒体氧化应激及抗氧化水平,并观察各组大鼠整体及骨骼肌胰岛素敏感性的变化.结果 与NC组相比,HF组大鼠胰岛素敏感性明显下降(P<0.05),SS及IMF线粒体活性氧簇(ROS)和丙二醛的水平明显增

  17. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

    Science.gov (United States)

    Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

    2014-12-01

    Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml-1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

  18. Analysis of resveratrol and radiation effects in lung cancer cells by micronucleus assay

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Carolina S.; Santos, Dymes R.A.; Vieira, Daniel P.; Rogero, Sizue O.; Rogero, Jose R., E-mail: carolina_sm@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Sakuraba, Roberto K.; Weltman, Eduardo [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Cruz, Aurea S.; Santos, Rezolina P. [Instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2015-07-01

    Mucoepidermoid lung carcinoma is frequently manifested by obstructive trachea symptoms. Radiation and drugs combinations are commonly used in the lung cancer treatment. Currently there is a strong tendency to develop therapeutic strategies focused at the administration of high potential compounds to improve the ionizing radiation treatments, so as to increase the radiation effects on tumor cell while minimizing these effects to surrounding normal tissues. Resveratrol is a polyphenolic phytoalexin compound present in wines and several plants. This compound has a broad spectrum of biological activities such as antioxidant, anticarcinogenic, and induction of cell cycle arrest effects. Analysis of biological effects of ionizing radiation in the presence of resveratrol in different cell cultures has been the subject of many studies. To verify the genotoxic effects in cells exposed to ionizing radiation many methods have been proposed. The cytokinesis-block micronucleus technique is one of the preferred methods. The main of this study was to detect and quantify radioinduced DNA damage in mucoepidermoid lung carcinoma cells (NCI-H292) by cytokinesis-block micronucleus technique using cytocalasin-B. The cell culture was irradiated at a single fraction from a TrueBeam® linear accelerator (0, 0.8, 5, and 10 Gy), in the absence or presence of different resveratrol concentrations (0, 15, 30, and 60 μM). The results showed that resveratrol (15 and μM) induced significant increase frequency (p<0.05) of micronucleus formation in NCI-H292 cell culture non-irradiated and exposed at 5 Gy dose. Moreover, resveratrol (30 μM) induced micronucleus formation at 0.8 Gy dose. (author)

  19. Resveratrol preserves the function of human platelets stored for transfusion.

    Science.gov (United States)

    Lannan, Katie L; Refaai, Majed A; Ture, Sara K; Morrell, Craig N; Blumberg, Neil; Phipps, Richard P; Spinelli, Sherry L

    2016-03-01

    Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function. Human platelets treated with resveratrol and stored for 5 d released less thromboxane B2 and prostaglandin E2 compared to control platelets. Resveratrol preserved the ability of platelets to aggregate, spread and respond to thrombin, suggesting an improved ability to activate post-storage. Utilizing an in vitro model of transfusion and thromboelastography, clot strength was improved with resveratrol treatment compared to conventionally stored platelets. The mechanism of resveratrol's beneficial actions on stored platelets was partly mediated through decreased platelet apoptosis in storage, resulting in a longer half-life following transfusion. Lastly, an in vivo mouse model of transfusion demonstrated that stored platelets are prothrombotic and that resveratrol delayed vessel occlusion time to a level similar to transfusion with fresh platelets. We show resveratrol has a dual ability to reduce unwanted platelet activation during storage, while preserving critical haemostatic function. PMID:26683619

  20. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling.

    Science.gov (United States)

    Wang, Gang; Chen, Ling; Pan, Xiaoyu; Chen, Jiechun; Wang, Liqun; Wang, Weijie; Cheng, Ruochuan; Wu, Fan; Feng, Xiaoqing; Yu, Yingcong; Zhang, Han-Ting; O'Donnell, James M; Xu, Ying

    2016-04-01

    Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling. PMID:26980711

  1. Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance

    Directory of Open Access Journals (Sweden)

    S Srivastava

    2009-01-01

    Full Text Available Background: Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics stage in Carcinoma Cervix (Ca Cx, and its significance as a prognostic marker, is not clear and needs an in-depth study. Aim: To correlate the blood levels of Lipid Peroxidation (LPO, Reduced Glutathione (GSH, Superoxide Dismutase (SOD, and Vitamin A and E levels with the clinical stage in Ca Cx. Settings and Design: This is a Prospective Case Control Study. Materials and Methods: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC. Statistical Analysis: The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. Results: The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. Conclusion: Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL.

  2. Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin

    NARCIS (Netherlands)

    Friedrich, R.B.; Kann, B.; Coradini, K.; Offerhaus, H.L.; Beck, R.C.R.; Windbergs, M.

    2015-01-01

    Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual the

  3. De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Li, Mingji; Kildegaard, Kanchana Rueksomtawin; Chen, Yun;

    2015-01-01

    Resveratrol is a natural antioxidant compound, used as food supplement and cosmetic ingredient. Microbial production of resveratrol has until now been achieved by supplementation of expensive substrates, p-coumaric acid or aromatic amino acids. Here we engineered the yeast Saccharomyces cerevisiae...... to produce resveratrol directly from glucose or ethanol via tyrosine intermediate. First we introduced the biosynthetic pathway, consisting of tyrosine ammonia-lyase from Herpetosiphon aurantiacus, 4-coumaryl-CoA ligase from Arabidopsis thaliana and resveratrol synthase from Vitis vinifera, and obtained 2.......73±0.05 mg L−1 resveratrol from glucose. Then we over-expressed feedback-insensitive alleles of ARO4 encoding 3-deoxy-D-arabino-heptulosonate-7-phosphate and ARO7 encoding chorismate mutase, resulting in production of 4.85±0.31 mg L−1 resveratrol from glucose as the sole carbon source. Next we improved...

  4. Resveratrol inhibits hyperglycemia-driven ROS-induced invasion and migration of pancreatic cancer cells via suppression of the ERK and p38 MAPK signaling pathways.

    Science.gov (United States)

    Cao, Lei; Chen, Xin; Xiao, Xue; Ma, Qingyong; Li, Wei

    2016-08-01

    Increasing evidence suggests that there is a strong relationship between diabetes mellitus (DM) and pancreatic cancer. Our previous study revealed that hyperglycemia could enhance the invasive and migratory activities of pancreatic cancer cells. Resveratrol, a natural polyphenolic phytoalexin, has many biological and pharmaceutical properties, including antioxidant and anti-tumorigenic capabilities. The aim of the present study was to evaluate whether resveratrol affects hyperglycemia-induced reactive oxygen species (ROS) production as well as the invasion and migration of pancreatic cancer and its underlying mechanisms. Human pancreatic cancer Panc-1 cells were exposed to high glucose condition with or without resveratrol, N-acetylcysteine (NAC, a scavenger of free radicals), PD 98059 (an ERK inhibitor) or SB 203580 (a p38 MAPK inhibitor). The intracellular ROS and hydrogen peroxide (H2O2) were determined using 2,7-dichlorodihydrofluorecein diacetate and H2O2 assay. MTT, wound healing assay and transwell matrigel invasion assay were used to detect the proliferation, migration and invasion potential of cancer cells. The expressions of uPA, E-cadherin and Glut-1 were examined using QT-PCR and western blot analysis at mRNA and protein levels. The activation of p-ERK, p-p38 and p-NF-κB were measured by western blot analysis. The results of the present study showed that resveratrol could significantly decrease high glucose-induced production of ROS and H2O2 in Panc-1 cells. Resveratrol was also able to inhibit high glucose-induced proliferation, migration and invasion of pancreatic cancer cells. High glucose-modulated expression of uPA, E-cadherin and Glut-1 were inhibited by resveratrol. In addition, high glucose-induced activation of ERK and p38 MAPK signaling pathways as well as the transcription factor NF-κB could also be suppressed by resveratrol. Furthermore, resveratrol was able to suppress H2O2-induced migration and invasion abilities of pancreatic cancer

  5. Antidepressant Effects of Resveratrol in an Animal Model of Depression

    Science.gov (United States)

    Akinfiresoye, Laura L. Hurley, Luli; Kalejaiye, Olubukola; Tizabi, Yousef

    2014-01-01

    Resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a natural non-flavonoid polyphenol antioxidant extracted from red grapes in the processing of wine. Initially it was studied for its potential as anticancer drug, and later was found to reduce cardiovascular disease. More recently resveratrol was shown to alleviate depressive-like symptoms induced by stress or other means in mice and rats. The major purpose of this study was to investigate whether resveratrol would manifest an antidepressant effect in Wistar-Kyoto (WKY) rats, a putative and non-induced animal model of depression, and whether this effect might be associated with an increase in hippocampal and frontal cortical brain-derived neurotrophic factor (BDNF), a protein implicated in chronic effects of many antidepressants. Adult male WKY rats were injected with two doses of resveratrol (10 and 40 mg/kg, i.p.) and their behavior in the open field locomotor activity (LMA), forced swim test (FST: a measure of helplessness), and sucrose preference test (SPT: a measure of anhedonia) was evaluated after a single acute injection or following 7 days of daily treatment. Both acute and chronic administration of resveratrol resulted in a dose-dependent decrease in FST. However, only chronic resveratrol resulted in dose-dependent increase in sucrose consumption. LMA was not affected by any treatment. Parallel to the observed behavioral effects the level of hippocampal, but not frontal cortical, BDNF was also dose-dependently elevated after chronic resveratrol administration. These findings indicate an antidepressant-like effect of resveratrol in an animal model of depression possibly via activation of hippocampal BDNF, and suggest therapeutic potential of resveratrol in at least a subpopulation of depressed patients. PMID:24717328

  6. Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models.

    Science.gov (United States)

    Singh, Nilendra; Agrawal, Megha; Doré, Sylvain

    2013-08-21

    Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action.

  7. Resveratrol provoca efeitos antiaterogênicos em um modelo animal de aterosclerose Resveratrol causes antiatherogenic effects in an animal model of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rossane Serafim Matos

    2012-02-01

    Full Text Available FUNDAMENTO: O resveratrol protege o sistema cardiovascular por meio de uma série de mecanismos, incluindo atividades antioxidantes e antiplaquetárias. OBJETIVO: Avaliar os possíveis efeitos anti-inflamatórios e antiaterogênicos do resveratrol, utilizando coelhos alimentados com uma dieta hipercolesterolêmica (1% de colesterol. MÉTODOS: Vinte coelhos brancos adultos do sexo masculino foram selecionados e divididos em dois grupos: grupo controle (GC, 10 coelhos; e grupo resveratrol (GR, 10 coelhos. Os animais foram alimentados com uma dieta hipercolesterolêmica por 56 dias. Para a dieta do GR, o resveratrol (2mg/kg peso/dia foi adicionado do 33º ao 56º dia. RESULTADOS: Não houve diferença significativa entre os grupos no colesterol sérico total, no colesterol HDL, no colesterol LDL e nos triglicerídeos. No GC, 70% apresentaram lesões ateroscleróticas avançadas da aorta (tipos III, IV, V ou VI. Todos os animais do GR apresentaram lesões ateroscleróticas leves da aorta (tipos I ou II ou não apresentaram lesões. A razão entre a área intimal e a área da camada intimal/medial mostrou-se significativamente menor no GR quando comparada ao GC (p BACKGROUND: Resveratrol protects the cardiovascular system by a number of mechanisms, including antioxidant and anti-platelet activities. OBJECTIVE: To assess the potential anti-inflammatory and antiatherogenic effects of resveratrol using rabbits fed a hypercholesterolemic diet (1% cholesterol. METHODS: Twenty white male rabbits were selected and divided into two groups: control group (CG, 10 rabbits; and resveratrol group (RG, 10 rabbits. The animals were fed a hypercholesterolemic diet for 56 days. For the RG diet, resveratrol (2mg/kg weight/day was added from days 33 - 56. RESULTS: There was no significant difference in the total serum cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides between the groups. Of the CG, 70% had advanced aortic atherosclerotic lesions (types

  8. Resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking IKKs/NF-κB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available Polydatin and resveratrol, as major active components in Polygonum cuspidatum, have anti-inflammatory, antioxidant and antitumor functions. However, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (EV71 have not been reported. In this study, resveratrol revealed strong antiviral activity on EV71, while polydatin had weak effect. Neither polydatin nor resveratrol exhibited influence on viral attachment. Resveratrol could effectively inhibit the synthesis of EV71/VP1 and the phosphorylation of IKKα, IKKβ, IKKγ, IKBα, NF-κB p50 and NF-κB p65, respectively. Meanwhile, the remarkably increased secretion of IL-6 and TNF-α in EV71-infected rhabdosarcoma (RD cells could be blocked by resveratrol. These results demonstrated that resveratrol inhibited EV71 replication and cytokine secretion in EV71-infected RD cells through blocking IKKs/NF-κB signaling pathway. Thus, resveratrol may have potent antiviral effect on EV71 infection.

  9. Antioxidants

    Science.gov (United States)

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  10. Effects of resveratrol, an important component of red wine, on intestinal cancer development

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhang

    2009-04-01

    Full Text Available Xiaoying Zhang1, Jan Anderson1, Radhey S Kaushik2,3, Chandradhar Dwivedi11Department of Pharmaceutical Sciences; 2Department of Veterinary Sciences; 3Department of Biology/Microbiology, South Dakota State University, Brookings, SD, USAAbstract: Resveratrol, a natural product derived from grapes and an important component of red wine, has been shown to inhibit cyclooxygenase and prevent various cancers. The purpose of this study is to investigate the effects of dietary grape extract, a source of resveratrol on intestinal cancer development in rats and to determine effects of resveratrol on cell growth in human colonic adenocarcinoma (Caco-2 cells, thus elucidating possible mechanisms of action of resveratrol. Results showed that dietary grape extract (5%, about 7 μg resveratrol consumed daily significantly decreased the incidence and multiplicity of tumors in small intestine in rats and resveratrol significantly inhibited cell viability and cell proliferation in Caco-2 cells.Keywords: resveratrol, grapes, colonic adenocarcinoma, Caco-2 cells

  11. Resveratrol inhibits nonalcoholic fatty liver disease in rats

    Directory of Open Access Journals (Sweden)

    Irastorza Belen

    2008-09-01

    Full Text Available Abstract Background The prevalence of nonalcoholic fatty liver disease (NAFLD is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor α (TNF-α production, lipid peroxidation and oxidative stress. Methods Male Wistar CRL: Wi (Han (225 g rats were randomized into three groups. A control group (n = 12 was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12 and resveratrol (n = 12 groups were given free access to feed (a high carbohydrate-fat free modified diet and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-α in serum, hepatic malondialdehyde (MDA, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase and biochemical parameters were measured. Results Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P P P P Conclusion Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-α inhibition and antioxidant activities.

  12. Resveratrol: A medical drug for acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Zhen-Hua Ma; Qing-Yong Ma

    2005-01-01

    Accumulating evidence demonstrates that resveratrol, a natural polyphenolic compound exracted from plants, inhibit inflammation when administered. It has direct effects on suppression of platelet coagulation and cytokines production in many experimental models. Because microcirculation occlusion and cytokines over-production is involved in many diseases such as acute pancreatitis (AP), the discovery of resveratrol as platelet and cytokines inhibitors has shed light on the treatment of AP, which still has significant mortality and morbidity. It is anticipated that this natural polyphenol could serve as a therapeutic compound in managing AP through different pathways.

  13. Effect of dietary resveratrol in ameliorating aflatoxin B1-induced changes in broiler birds.

    Science.gov (United States)

    Sridhar, M; Suganthi, R U; Thammiaha, V

    2015-12-01

    Consumption of aflatoxin B1 (AFB1) contaminated feed by poultry affects the health of broiler birds causing severe economic losses. The use of phytochemicals is a safe, effective, alternative and practical approach to combat the toxic effect of AF in broilers. Resveratrol, a polyphenol derived from red grapes, berries and peanuts, exerts anti-inflammatory, antioxidant and immunomodulatory effects. Our study was aimed at evaluating the possible protective effects of resveratrol against the adverse effects of AFB1 in broiler birds. A feeding trial of 42 days of duration was undertaken in a completely randomized design with five dietary treatments: G1-AFB1(1.0 ppm); G2-CTR (basal diet alone); G3-AFB1(1.0 ppm)+Resv 0.5%; G4-AFB1(1.0 ppm)+Resv 1%; and G5-Resv 1%. Gain in body weight (BWG) and feed intake (FI) was observed to be highest (p Feed conversion ratio was lowest in G2-CTR birds and failed to record any significant variation (p > 0.05) between groups as well as within groups. Birds fed resveratrol at both 0.5% and 1.0% levels in combination with AFB1 as well as alone along with basal diet had lower BWG and FI between the fourth and fifth week and also at the fifth week (p 0.05) was obtained in the FCR of AFB1 and resveratrol group of broiler birds. AFB1 feeding significantly increased the activities of aspartate-(AST) and alanine-(ALT) amino transferase, superoxide dismutase (SOD) and catalase (CAT) activities (p feed additive to control aflatoxicosis in poultry farms. PMID:25319220

  14. Consumer Acceptance of Bars and Gummies with Unencapsulated and Encapsulated Resveratrol.

    Science.gov (United States)

    Koga, Clarissa C; Lee, Soo-Yeun; Lee, Youngsoo

    2016-05-01

    The addition of resveratrol, a polyphenol found in red wine and peanuts, to food products would help to provide the health benefits associated with the compound to the consumer in a wide array of food matrices. The bitterness of resveratrol and instability of its bioactive form in light are 2 major challenges with the incorporation of the compound into food products. Microencapsulation in a sodium caseinate matrix was utilized as a strategy to overcome these challenges. The objective of this research was to show the application of the resveratrol microcapsules in easy-to-consume foods. Consumer acceptance was evaluated for gummies and bars with encapsulated resveratrol in comparison to the controls. Four different controls were used: 1) without any resveratrol OR protein (Plain), 2) unencapsulated resveratrol (Resv), 3) sodium caseinate and unencapsulated resveratrol just mixed without encapsulation (P + R), and 4) sodium caseinate only (PRO). Two concentrations of resveratrol that have been shown to offer therapeutic effects in humans were tested (10 and 40 mg/d). The overall liking, evaluated using a 9-point scale, of bars with 10 mg of encapsulated resveratrol did not differ significantly from the control without any added resveratrol and protein (Plain) or from the controls with equivalent protein and/or resveratrol concentrations. For gummies, the samples with the resveratrol microcapsules had a significantly lower overall liking than the controls with the same protein and/or resveratrol content. This research demonstrated application of resveratrol microcapsules into easy-to-consume food products in order to deliver the health benefits to the consumer. PMID:27003921

  15. Consumer Acceptance of Bars and Gummies with Unencapsulated and Encapsulated Resveratrol.

    Science.gov (United States)

    Koga, Clarissa C; Lee, Soo-Yeun; Lee, Youngsoo

    2016-05-01

    The addition of resveratrol, a polyphenol found in red wine and peanuts, to food products would help to provide the health benefits associated with the compound to the consumer in a wide array of food matrices. The bitterness of resveratrol and instability of its bioactive form in light are 2 major challenges with the incorporation of the compound into food products. Microencapsulation in a sodium caseinate matrix was utilized as a strategy to overcome these challenges. The objective of this research was to show the application of the resveratrol microcapsules in easy-to-consume foods. Consumer acceptance was evaluated for gummies and bars with encapsulated resveratrol in comparison to the controls. Four different controls were used: 1) without any resveratrol OR protein (Plain), 2) unencapsulated resveratrol (Resv), 3) sodium caseinate and unencapsulated resveratrol just mixed without encapsulation (P + R), and 4) sodium caseinate only (PRO). Two concentrations of resveratrol that have been shown to offer therapeutic effects in humans were tested (10 and 40 mg/d). The overall liking, evaluated using a 9-point scale, of bars with 10 mg of encapsulated resveratrol did not differ significantly from the control without any added resveratrol and protein (Plain) or from the controls with equivalent protein and/or resveratrol concentrations. For gummies, the samples with the resveratrol microcapsules had a significantly lower overall liking than the controls with the same protein and/or resveratrol content. This research demonstrated application of resveratrol microcapsules into easy-to-consume food products in order to deliver the health benefits to the consumer.

  16. Tristetraprolin: a novel mediator of the anticancer properties of resveratrol.

    Science.gov (United States)

    Li, C; Tang, C; He, G

    2016-01-01

    Resveratrol is a natural compound that exhibits anticancer properties. Previous studies have proved that it can inhibit the proliferation of breast cancer cell lines and upregulate some cytokines such as cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). The initiation and progression of cancer are associated with the abnormal expression of multiple cytokines. Tristetraprolin (TTP), an mRNA-binding protein, is one of the key proteins that participate in regulating cytokine expression. Two different proliferation assays on MCF-7 cells showed that the cell proliferation rate significantly reduced following treatment with resveratrol. Most importantly, we found that resveratrol promoted TTP expression at both the mRNA and protein level in a dose- and time-dependent manner. In addition, the expression of COX-2 and VEGF were significantly suppressed by resveratrol while that of inducible nitric oxide synthase (iNOS) was upregulated. Lastly, the effects of resveratrol on both MCF-7 proliferation and expression of COX-2, VEGF, and iNOS were significantly inhibited by TTP knockdown, indicating that TTP mediates the anticancer properties of resveratrol. In summary, we conclude that resveratrol inhibits the proliferation of MCF-7 cells by TTP upregulation, which is associated with downregulation of COX-2 and VEGF and upregulation of iNOS. PMID:27323060

  17. What is new for resveratrol?

    DEFF Research Database (Denmark)

    Vang, Ole

    2013-01-01

    Numerous scientific papers have suggested health-promoting effects of resveratrol, including claims in the prevention of diseases such as coronary heart disease, diabetes, and cancer. Therefore, it was proposed that the scientific community needed to express recommendations on the human use...... of resveratrol. Such recommendations were formulated after the first international resveratrol conference in Denmark, Resveratrol2010. The working group stated that the evidence was "not sufficiently strong to justify recommendation for the chronic administration of resveratrol to human beings, beyond the dose...... which can be obtained from dietary sources." It was a disappointing conclusion relative to the positive claims about the therapeutic potential of resveratrol made by the media. However, since 2010, results from the first clinical trials on resveratrol have been made available. Because of these emerging...

  18. What is new for resveratrol?

    DEFF Research Database (Denmark)

    Vang, Ole

    2013-01-01

    Numerous scientific papers have suggested health-promoting effects of resveratrol, including claims in the prevention of diseases such as coronary heart disease, diabetes, and cancer. Therefore, it was proposed that the scientific community needed to express recommendations on the human use of...... resveratrol. Such recommendations were formulated after the first international resveratrol conference in Denmark, Resveratrol2010. The working group stated that the evidence was "not sufficiently strong to justify recommendation for the chronic administration of resveratrol to human beings, beyond the dose...... which can be obtained from dietary sources." It was a disappointing conclusion relative to the positive claims about the therapeutic potential of resveratrol made by the media. However, since 2010, results from the first clinical trials on resveratrol have been made available. Because of these emerging...

  19. Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

    OpenAIRE

    Hogg, Simon J.; Kenny Chitcholtan; Wafaa Hassan; Sykes, Peter H.; Ashley Garrill

    2015-01-01

    Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results...

  20. Trimethoxy-resveratrol and piceatannol administered orally suppress and inhibit tumor formation and growth in prostate cancer xenografts

    Science.gov (United States)

    Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is still unknown. METHODS. We synthesized natural and synthetic anal...

  1. Production of Resveratrol by Piceid Deglycosylation Using Cellulase

    Directory of Open Access Journals (Sweden)

    Chia-Hung Kuo

    2016-02-01

    Full Text Available Resveratrol is a dietary polyphenolic compound widely used in medicine, food, and cosmetic products. The glycoside form of resveratrol, piceid, is also present in several plant materials but is less bioavailable. In this study, enzymatic transformation of piceid into resveratrol using inexpensive cellulase was investigated. Response surface methodology was used to evaluate the effect of reaction parameters, including reaction temperature, reaction time, enzyme amount and pH. The optimal conditions for biotransformation of piceid to resveratrol are: a reaction temperature of 50 °C, reaction time of 4.75 h, enzyme amount of 2.5 fungal β-glucanase (FBG units and pH of 4.3. In addition, the extracts from Polygonum cuspidatum root contained high amounts of piceid were treated with cellulase in order to deglycosylation that increased resveratrol yield. After treatment, the resveratrol yield significantly increased from 2.72 to 9.49 mg/g, while the piceid contents decreased from 8.60 to 0 mg/g. The result provides an efficient method to convert piceid in the extracts of P. cuspidatum root into resveratrol by cellulase.

  2. Resveratrol, MicroRNAs, Inflammation, and Cancer

    Directory of Open Access Journals (Sweden)

    Esmerina Tili

    2011-01-01

    Full Text Available MicroRNAs are short noncoding RNAs that regulate the expression of many target genes posttranscriptionally and are thus implicated in a wide array of cellular and developmental processes. The expression of miR-155 or miR-21 is upregulated during the course of the inflammatory response, but these microRNAs are also considered oncogenes due to their upregulation of expression in several types of tumors. Furthermore, it is now well established that inflammation is associated with the induction or the aggravation of nearly 25% of cancers. Therefore, the above microRNAs are thought to link inflammation and cancer. Recently, resveratrol (trans-3,4′,5-trihydroxystilbene, a natural polyphenol with antioxidant, anti-inflammatory, and anticancer properties, currently at the stage of preclinical studies for human cancer prevention, has been shown to induce the expression of miR-663, a tumor-suppressor and anti-inflammatory microRNA, while downregulating miR-155 and miR-21. In this paper we will discuss how the use of resveratrol in therapeutics may benefit from the preanalyses on the status of expression of miR-155 or miR-21 as well as of TGFβ1. In addition, we will discuss how resveratrol activity might possibly be enhanced by simultaneously manipulating the levels of its key target microRNAs, such as miR-663.

  3. Red wine extract, resveratrol, on maintenance of organ function following trauma-hemorrhage

    Directory of Open Access Journals (Sweden)

    Fu-Chao Liu

    2012-10-01

    Full Text Available ABSTRACT:Resveratrol, is a polyphenol that can be extracted from grapes and red wine, possess potential anti-inflammatory effects, which would result in the reduction of cytokine production, the alteration of the expression of adhesion molecule molecules, and the inhibition of neutrophil function. Resveratrol might also act as an antioxidant, anti-aging, and control of cell cycle and apoptosis. Resveratrol has been shown to have protective effects for patients inshock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the regulation of the mitogen-activated protein kinases (MAPK/ hemeoxygenase-1 (HO-1 pathway, activates estrogen receptor (ER, and the mediation of pro-inflammatory cytokines, reactive oxygen species (ROS formation and reactive. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to maintain organ function following trauma-hemorrhage.

  4. Neuroprotective effects of Resveratrol in Alzheimer Disease Pathology

    Directory of Open Access Journals (Sweden)

    Shraddha D Rege

    2014-09-01

    Full Text Available Alzheimer’s disease (AD is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4’-trihydroxy-trans-stilbene when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogues aimed at increasing bioavailability in plasma is also discussed.

  5. Neuroprotective effects of resveratrol in Alzheimer disease pathology

    Science.gov (United States)

    Rege, Shraddha D.; Geetha, Thangiah; Griffin, Gerald D.; Broderick, Tom L.; Babu, Jeganathan Ramesh

    2014-01-01

    Alzheimer’s disease is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4′-trihydroxy-trans-stilbene) when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogs aimed at increasing the bioavailability in plasma is also discussed. PMID:25309423

  6. Resveratrol: A review of preclinical studies for human cancer prevention

    International Nuclear Information System (INIS)

    The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds one of which is resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits. Resveratrol is known to have potent anti-inflammatory and antioxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells. Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion, and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers. Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways. This review discusses the current preclinical and mechanistic data available and assesses resveratrol's anticancer effects to support its potential as an anticancer agent in human populations

  7. Vitamin C and resveratrol supplementation to rat dams treated with di(2-ethylhexyl)phthalate: impact on reproductive and oxidative stress end points in male offspring.

    Science.gov (United States)

    Botelho, Giuliana G K; Bufalo, Aedra C; Boareto, Ana Claudia; Muller, Juliane C; Morais, Rosana N; Martino-Andrade, Anderson J; Lemos, Karen R; Dalsenter, Paulo R

    2009-11-01

    This study was carried out to assess the influence of di(2-ethylhexyl)phthalate (DEHP) alone or associated with antioxidants on the male reproductive system in newborn rats, emphasizing the implications of oxidative stress and hormonal balance during prenatal and early postnatal periods. Wistar females were exposed by oral route to DEHP alone or associated with antioxidants from gestational day 7 to lactational day 2 according to the following treatment regimens: (C) vehicle control (canola oil + 1% Tween-80); (V) vitamin C (200 mg/kg) + canola oil; (R) resveratrol (10 mg/kg) + canola oil; (D) DEHP (500 mg/kg) + 1% Tween-80; (DV) DEHP (500 mg/kg) + vitamin C (200 mg/kg); and (DR) DEHP (500 mg/kg) + resveratrol (10 mg/kg). Two male pups per litter were randomly selected and necropsied on postnatal day 2. The brain and liver were removed and weighed and anogenital distance (AGD) was measured. Additionally, the testes were removed for assessment of intratesticular testosterone levels and histopathology; the liver was used to measure biomarkers of oxidative stress. Vitamin C and resveratrol alone did not affect the reproductive end points and did not induce oxidative stress. Exposure of dams to DEHP alone and associated with antioxidants resulted in hepatomegaly in offspring and significantly increased the incidence of multinucleated gonocytes in seminiferous cords. Testosterone and AGD presented a trend to decrease in DEHP-exposed groups. Catalase activity increased only in groups exposed to DEHP associated with antioxidants, although GST (gluthatione-S-transferase) activity decreased in all DEHP-exposed groups. The levels of hydroperoxides increased only in group exposed to DEHP associated with vitamin C. These results indicate that the association of DEHP with antioxidants was unable to ameliorate DEHP-induced reproductive changes, and the coadministration of DEHP and these antioxidants might even contribute to an overall increase in oxidative stress. PMID:19756843

  8. Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

    Science.gov (United States)

    Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

    2015-08-01

    Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

  9. Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Xingrong Ma; Zhikun Sun; Yanru Liu; Yanjie Jia; Boai Zhang; Jiewen Zhang

    2013-01-01

    Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson’s disease, cerebral ischemia and Alzheimer’s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8–12 weeks after model induction, rats were intragastrical y administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro-longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

  10. trans-Resveratrol in Nutraceuticals: Issues in Retail Quality and Effectiveness

    Directory of Open Access Journals (Sweden)

    Gianni Sacchetti

    2012-10-01

    Full Text Available Fourteen brands of resveratrol-containing nutraceuticals were evaluated in order to verify their actual resveratrol content and to control if their health-promoting properties are related to manufacturing quality. Products included pure resveratrol capsules or multi-ingredient formulations with standardized amounts of resveratrol and other phytochemicals. Samples were analyzed for total trans-resveratrol, flavonoids, procyanidin, polyphenol content and the results were compared with the content declared on-label. Only five out of 14 brands had near label values, compliant with Good Manufacturing Practices (GMP requirements (95–105% content of active constituent, four products were slightly out of this range (83–111% and three were in the 8–64% range. Two samples were below the limit of detection. The greater the difference between actual and labeled resveratrol content, the lower was the antioxidant and antiproliferative activity strength. Dietary supplements containing pure trans-resveratrol exhibited a greater induction of differentiation towards human leukemic K562 cells when compared to multicomponent products. Great differences currently exist among resveratrol food supplements commercially available and GMP-grade quality should not be taken for granted. On the other side, dosages suggested by most “pure”, “high-dosage” supplements may allow a supplementation level adequate to obtain some of the purported health benefits.

  11. Radiomodifying effect of resveratrol in human rhabdomyosarcoma (RD) cell culture applying the comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, Vanessa D.; Rogero, Sizue O.; Vieira, Daniel P.; Okazaki, Kayo; Rogero, Jose R., E-mail: van.biologa@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Cruz, Aurea S., E-mail: aurcruz@ial.sp.gov.br [Instituto Adolfo Lutz (IAL-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Cancer is considered a worldwide public health problem. Resveratrol is a defense polyphenol, synthesized naturally by a wide variety of plants according to response of ultraviolet radiation (UV) exposition or according to mechanical stress resulting of pathogens or chemical and physical agents. In vines this substance is found in elevated concentration. Thus, resveratrol is present in grape juice and wines, especially red wine. Red wines are the best dietary source of resveratrol.The protective effects performed by resveratrol during the process of cell damage, produced by oxidative effects of free radicals, are anti-inflammatory, anti-platelet and anti-carcinogenic activity, prevent or inhibit degenerative diseases, decrease incidence of cardiovascular diseases. Moreover, resveratrol is considered as a cell radioprotector. On the other hand, in some elevated concentrations resveratrol is considered as a radiosensitizing compound. The aim of this work was study in vitro the radiomodifying effect of resveratrol in human rhabdomyosarcoma (RD) cells applying the comet assay to evaluate the cellular damage and its repair capacity. In this study RD cells culture was irradiated by gamma radiation at 50 Gy and 100 Gy doses and the used resveratrol concentrations was from 15 μM to 60 μM. The protective and radioprotective effects were observed at 15 μM and 30 μM resveratrol concentrations. The resveratrol concentration of 60 μM showed cytotoxic effect to RD tumor cells and with gamma radiation presence this concentration showed no statistically significant radiosensitizing effects. (author)

  12. A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine

    DEFF Research Database (Denmark)

    Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

    2007-01-01

    Resveratrol, a naturally occurring compound of various fruits such as grapes, is thought to possess chemopreventive properties. The levels of resveratrol in grapes and grape products including wine, varies from region to region and from one year to another. This paper reviews the resveratrol...... content in red wine based on relevant published data. Red wine contains an average of 1.9 ± 1.7 mg trans-resveratrol/ l (8.2 ± 7.5 lM), ranging from non-detectable levels to 14.3 mg/l (62.7 lM) trans-resveratrol. In general, wines made from grapes of the Pinot Noir and St. Laurent varieties showed...... the highest level of trans-resveratrol. No region can be said to produce wines with significantly higher level of trans-resveratrol than all other regions. Levels of cis-resveratrol follow the same trend as trans-resveratrol. The average level of trans-resveratrol-glucoside (trans-piceid) in a red wine may...

  13. What is new for an old molecule? Systematic review and recommendations on the use of resveratrol.

    Directory of Open Access Journals (Sweden)

    Ole Vang

    Full Text Available BACKGROUND: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. METHODOLOGY: Literature search in databases as PUBMED and ISI Web of Science in combination with manual search was used to answer the following five questions: (1Can resveratrol be recommended in the prevention or treatment of human diseases?; (2Are there observed "side effects" caused by the intake of resveratrol in humans?; (3What is the relevant dose of resveratrol?; (4What valid data are available regarding an effect in various species of experimental animals?; (5Which relevant (overall mechanisms of action of resveratrol have been documented? CONCLUSIONS/SIGNIFICANCE: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.

  14. Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats

    OpenAIRE

    Zhang, Weiqian; Liu, Yan; Ge, Ming; Jing, Jiang; Chen, Yan; Jiang, Huijie; Yu, Hongxiang; Li, Ning; Zhang, Zhigang

    2014-01-01

    BACKGROUD/OBEJECTIVES Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)-induced Male Wistar rats. MATERIALS/METHODS Adult rats received 3 mg/kg As2O3 (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv...

  15. Seedless synthesis of gold nanorods using resveratrol as a reductant

    Science.gov (United States)

    Wang, Wenjing; Li, Jing; Lan, Shijie; Rong, Li; Liu, Yi; Sheng, Yu; Zhang, Hao; Yang, Bai

    2016-04-01

    Gold nanorods (GNRs) attract extensive attention in current diagnostic and therapeutic applications which require the synthesis of GNRs with high yields, adjustable aspect ratio, size monodispersity, and easy surface decoration. In the seed-mediated synthesis of GNRs using cetyl trimethyl ammonium bromide (CTAB) micelles as templates, the additives of aromatic compounds have been found to be important for improving the size monodispersity of the as-synthesized GNRs; this is hopeful in terms of the further optimization of the synthetic methodology of GNRs. In this work, resveratrol, a natural polyphenol in grapes with an anti-oxidization behavior, is employed as the reductant for the seedless synthesis of GNRs with a good size monodispersity and a tunable aspect ratio. Accordingly, the longitudinal localized surface plasmon resonance (LSPR) peak is tunable from 570 to 950 nm. The success of our approach is attributed to the aromatic structure and mild reducibility of resveratrol. The embedment of resveratrol into CTAB micelles strengthens the facet-selective adsorption of CTAB, and therewith facilitates the anisotropic growth of GNRs. In addition, the mild reducibility of resveratrol is capable of supporting GNR growth by avoiding secondary nucleation, thus allowing the seedless synthesis of GNRs with a good size monodispersity. As a chemopreventive agent, the combination of resveratrol in GNR synthesis will consolidate the theranostic applications of GNRs.

  16. Dietary resveratrol prevents the development of food allergy in mice.

    Directory of Open Access Journals (Sweden)

    Yui Okada

    Full Text Available BACKGROUND: Resveratrol is a bioactive polyphenol enriched in red wine that exhibits many beneficial health effects via multiple mechanisms. However, it is unclear whether resveratrol is beneficial for the prevention of food allergy. This study investigated whether resveratrol inhibited the development of food allergy by using a mouse model of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Mice fed standard diet or standard diet plus resveratrol were sensitized by intragastric administration of ovalbumin (OVA and mucosal adjuvant cholera toxin (CT. Several manifestations of food allergy were then compared between the mice. The effects of resveratrol on T cells or dendritic cells were also examined by using splenocytes from OVA-specific T cell-receptor (TCR transgenic DO11.10 mice or mouse bone marrow-derived dendritic cells (BMDCs in vitro. We found that mice fed resveratrol showed reduced OVA-specific serum IgE production, anaphylactic reaction, and OVA-induced IL-13 and IFN-ã production from the mesenteric lymph nodes (MLNs and spleens in comparison to the control mice, following oral sensitization with OVA plus CT. In addition, resveratrol inhibited OVA plus CT-induced IL-4, IL-13, and IFN-ã production in splenocytes from DO11.10 mice associated with inhibition of GATA-3 and T-bet expression. Furthermore, resveratrol suppressed the OVA plus CT-induced CD25 expression and IL-2 production in DO11.10 mice-splenocytes in association with decreases in CD80 and CD86 expression levels. Finally, resveratrol suppressed CT-induced cAMP elevation in association with decreases in CD80 and CD86 expression levels in BMDCs. CONCLUSIONS/SIGNIFICANCE: Ingestion of resveratrol prevented the development of a food allergy model in mice. Given the in vitro findings, resveratrol might do so by inhibiting DC maturation and subsequent early T cell activation and differentiation via downregulation of CT-induced cAMP activation in mice. These results suggest that

  17. Resveratrol production in bioreactor: Assessment of cell physiological states and plasmid segregational stability

    OpenAIRE

    Margarida S. Afonso; Susana Ferreira; Domingues, Fernanda C.; Filomena Silva

    2015-01-01

    Resveratrol is a plant secondary metabolite commonly found in peanuts and grapevines with significant health benefits. Recombinant organisms can produce large amounts of resveratrol and, in this work, Escherichia coli BW27784 was used to produce resveratrol in bioreactors while monitoring cell physiology and plasmid stability through flow cytometry and real-time qPCR, respectively. Initially, the influence of culture conditions and precursor addition was evaluated in screening assays and the ...

  18. Protective activity of a novel resveratrol analogue, HS-1793, against DNA damage in 137Cs-irradiated CHO-K1 cells

    International Nuclear Information System (INIS)

    Resveratrol has received considerable attention as a polyphenol with anti-oxidant, anti-carcinogenic, and anti-inflammatory effects. Radiation is an important component of therapy for a wide range of malignant conditions. However, it causes damage to normal cells and, hence, can result in adverse side effects. This study was conducted to examine whether HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, induces a protective effect against radiation-induced DNA damage. HS-1793 effectively scavenged free radicals and inhibited radiation-induced plasmid DNA strand breaks in an in vitro assay. HS-1793 significantly decreased reactive oxygen species and cellular DNA damage in 2 Gy-irradiated Chinese hamster ovary (CHO)-K1 cells. In addition, HS-1793 dose-dependently reduced the levels of phosphorylated H2AX in irradiated CHO-K1 cells. These results indicate that HS-1793 has chemical radioprotective activity. Glutathione levels and superoxide dismutase activity in irradiated CHO-K1 cells increased significantly following HS-1793 treatment. The enhanced biological anti-oxidant activity and chemical radioprotective activity of HS-1793 maintained survival of irradiated CHO-K1 cells in a clonogenic assay. Therefore, HS-1793 may be of value as a radioprotector to protect healthy tissue surrounding tumor cells during radiotherapy to obtain better tumor control with a higher dose. (author)

  19. Metabolic engineering of resveratrol and other longevity boosting compounds.

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y; Chen, H; Yu, O

    2010-09-16

    Resveratrol, a compound commonly found in red wine, has attracted many attentions recently. It is a diphenolic natural product accumulated in grapes and a few other species under stress conditions. It possesses a special ability to increase the life span of eukaryotic organisms, ranging from yeast, to fruit fly, to obese mouse. The demand for resveratrol as a food and nutrition supplement has increased significantly in recent years. Extensive work has been carried out to increase the production of resveratrol in plants and microbes. In this review, we will discuss the biosynthetic pathway of resveratrol and engineering methods to heterologously express the pathway in various organisms. We will outline the shortcuts and limitations of common engineering efforts. We will also discuss briefly the features and engineering challenges of other longevity boosting compounds.

  20. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial.

    Science.gov (United States)

    Bo, S; Ponzo, V; Ciccone, G; Evangelista, A; Saba, F; Goitre, I; Procopio, M; Pagano, G F; Cassader, M; Gambino, R

    2016-09-01

    The polyphenol resveratrol is considered to exert many beneficial actions, such as antioxidant, anti-inflammatory, insulin-sensitizer and anticancer effects. Its benefits in patients with type 2 diabetes mellitus (T2DM) are controversial. Our aims were to determine whether resveratrol supplementation at two different dosages (500 and 40mg/day) for 6 months i) reduced the concentrations of C-reactive-protein (CRP) and ii) ameliorated the metabolic pattern of T2DM patients. In the present double-blind, randomized, placebo-controlled trial, 192 T2DM patients were randomized to receive resveratrol 500mg/day (Resv500arm), resveratrol 40mg/day (Resv40arm) or placebo for 6-months. At baseline and at the trial end, CRP values, anthropometric, metabolic and liver parameters were determined. No serious adverse event occurred. A dose-dependent, though not significant, CRP decrease of 5.6% (Resv40arm) and 15.9% (Resv500arm) was observed vs placebo. We failed to detect significant differences in weight, BMI, waist circumference, and values of arterial blood pressure, fasting glucose, glycated hemoglobin, insulin, C-peptide, free fatty acids, liver transaminases, uric acid, adiponectin, interleukin-6, in both the Resv500 and Resv40 arms vs placebo. Total cholesterol and triglycerides slightly increased in the Resv500arm. Subgroup analyses revealed that lower diabetes duration (in both Resv500 and Resv40arms), and, in the Resv500arm, younger age, aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo. The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations, nor improve the metabolic pattern of T2DM patients. PMID:27520400

  1. Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation

    Directory of Open Access Journals (Sweden)

    Mahesh Subramanian

    2014-01-01

    Full Text Available Resveratrol (5-[(E-2-(4-hydroxyphenylethenyl]benzene-1,3-diol, a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry and propidium iodide uptake (flow cytometry and microscopy as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.

  2. Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation.

    Science.gov (United States)

    Subramanian, Mahesh; Goswami, Manish; Chakraborty, Saikat; Jawali, Narendra

    2014-01-01

    Resveratrol (5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol), a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS) generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry) and propidium iodide uptake (flow cytometry and microscopy) as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.

  3. Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE * 3-Leiden.CETP mice

    NARCIS (Netherlands)

    Berbée, J.F.P.; Wong, M.C.; Wang, Y.; Hoorn, J.W.A. van der; Khedoe, P.P.S.J.; Klinken, J.B. van; Mol, I.M.; Hiemstra, P.S.; Tsikas, D.; Romijn, J.A.; Havekes, L.M.; Princen, H.M.G.; Rensen, P.C.N.

    2013-01-01

    Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects again

  4. Convergent Effects of Resveratrol and PYK2 on Prostate Cells.

    Science.gov (United States)

    Conte, Andrea; Kisslinger, Annamaria; Procaccini, Claudio; Paladino, Simona; Oliviero, Olimpia; de Amicis, Francesca; Faicchia, Deriggio; Fasano, Dominga; Caputo, Marilena; Matarese, Giuseppe; Pierantoni, Giovanna Maria; Tramontano, Donatella

    2016-01-01

    Resveratrol, a dietary polyphenol, is under consideration as chemopreventive and chemotherapeutic agent for several diseases, including cancer. However, its mechanisms of action and its effects on non-tumor cells, fundamental to understand its real efficacy as chemopreventive agent, remain largely unknown. Proline-rich tyrosine kinase 2 (PYK2), a non-receptor tyrosine kinase acting as signaling mediator of different stimuli, behaves as tumor-suppressor in prostate. Since, PYK2 and RSV share several fields of interaction, including oxidative stress, we have investigated their functional relationship in human non-transformed prostate EPN cells and in their tumor-prone counterpart EPN-PKM, expressing a PYK2 dead-kinase mutant. We show that RSV has a strong biological activity in both cell lines, decreasing ROS production, inducing morphological changes and reversible growth arrest, and activating autophagy but not apoptosis. Interestingly, the PYK2 mutant increases basal ROS and autophagy levels, and modulates the intensity of RSV effects. In particular, the anti-oxidant effect of RSV is more potent in EPN than in EPN-PKM, whereas its anti-proliferative and pro-autophagic effects are more significant in EPN-PKM. Consistently, PYK2 depletion by RNAi replicates the effects of the PKM mutant. Taken together, our results reveal that PYK2 and RSV act on common cellular pathways and suggest that RSV effects on prostate cells may depend on mutational-state or expression levels of PYK2 that emerges as a possible mediator of RSV mechanisms of action. Moreover, the observation that resveratrol effects are reversible and not associated to apoptosis in tumor-prone EPN-PKM cells suggests caution for its use in humans. PMID:27649143

  5. Convergent Effects of Resveratrol and PYK2 on Prostate Cells

    Science.gov (United States)

    Conte, Andrea; Kisslinger, Annamaria; Procaccini, Claudio; Paladino, Simona; Oliviero, Olimpia; de Amicis, Francesca; Faicchia, Deriggio; Fasano, Dominga; Caputo, Marilena; Matarese, Giuseppe; Pierantoni, Giovanna Maria; Tramontano, Donatella

    2016-01-01

    Resveratrol, a dietary polyphenol, is under consideration as chemopreventive and chemotherapeutic agent for several diseases, including cancer. However, its mechanisms of action and its effects on non-tumor cells, fundamental to understand its real efficacy as chemopreventive agent, remain largely unknown. Proline-rich tyrosine kinase 2 (PYK2), a non-receptor tyrosine kinase acting as signaling mediator of different stimuli, behaves as tumor-suppressor in prostate. Since, PYK2 and RSV share several fields of interaction, including oxidative stress, we have investigated their functional relationship in human non-transformed prostate EPN cells and in their tumor-prone counterpart EPN-PKM, expressing a PYK2 dead-kinase mutant. We show that RSV has a strong biological activity in both cell lines, decreasing ROS production, inducing morphological changes and reversible growth arrest, and activating autophagy but not apoptosis. Interestingly, the PYK2 mutant increases basal ROS and autophagy levels, and modulates the intensity of RSV effects. In particular, the anti-oxidant effect of RSV is more potent in EPN than in EPN-PKM, whereas its anti-proliferative and pro-autophagic effects are more significant in EPN-PKM. Consistently, PYK2 depletion by RNAi replicates the effects of the PKM mutant. Taken together, our results reveal that PYK2 and RSV act on common cellular pathways and suggest that RSV effects on prostate cells may depend on mutational-state or expression levels of PYK2 that emerges as a possible mediator of RSV mechanisms of action. Moreover, the observation that resveratrol effects are reversible and not associated to apoptosis in tumor-prone EPN-PKM cells suggests caution for its use in humans. PMID:27649143

  6. Resveratrol food supplements

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-01-01

    Background: Consumers increasingly choose food supplements in addition to their diet. Research on supplement users finds they are likely to be female, older and well-educated; Furthermore, supplement users are often characterised as being especially health-oriented, an observation which is termed...... the ‘inverse supplement hypothesis’. However, results are dependent on the substance in question. Little is known so far about botanicals in general, and more specifically, little is known about resveratrol. The psychographic variables of food supplement users are yet relatively underexplored. By comparing US...... and Danish respondents, we aimed to identify whether sociodemographic variables, health status, health beliefs and behaviour and interest in food aspects specifically relevant to resveratrol (e.g., naturalness, indulgence, and Mediterranean food) explain favourable attitudes and adoption intentions toward...

  7. Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Fangfang Lang

    Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

  8. Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.

    Directory of Open Access Journals (Sweden)

    Andrew Mamalis

    Full Text Available Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease.The goal of our study was to investigate the how reactive oxygen species (ROS free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed.High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR. For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2 on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2.High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched

  9. Factors Affecting Resveratrol Content in Strawberries

    Science.gov (United States)

    This study investigated the occurrence of resveratrol in Fragaria x ananassa Duchesne and the effect of preharvest conditions on resveratrol content. Both cis- and trans- resveratrol were detected in strawberry achenes (seeds) and pulp (receptacle tissue). Resveratrol was identified by LC-MS. Resver...

  10. Partitioning of resveratrol between pentane and DMSO

    DEFF Research Database (Denmark)

    Shen, Chen; Stein, Paul C.; Klösgen-Buchkremer, Beate Maria

    2015-01-01

    Partitioning of trans-3,5,4′-trihydroxy-stilbene (resveratrol) between n-pentane and DMSO was investigated as a contribution to understand the interaction between resveratrol and biomembranes. In order to determine the partition coefficient P* of resveratrol between pentane and DMSO, resveratrol...

  11. Avaliação da estabilidade e atividade antioxidante de uma emulsão base não-iônica contendo resveratrol

    Directory of Open Access Journals (Sweden)

    Marcela Kist Lange

    2009-03-01

    -ionic emulsion basis for assessing the profile of stability and antioxidant activity, as compared with a non-ionic basis emulsion containing BHT. The profile of stability was examined by the observation of the organoleptic characteristics, determination of pH and spreadability, and the antioxidant activity through the Radical Scavenging DPPH test. The results showed that the emulsion containing BHT was more stable than the emulsion containing resveratrol, when high temperature was used. For the analysis of the antioxidant activity, the resveratrol, in both forms of incorporation, showed significant antioxidant activity in comparison to BHT, suggesting that resveratrol may be a viable antioxidant alternative to be used into cosmetic preparations.

  12. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

    International Nuclear Information System (INIS)

    Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml−1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of −35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group. (paper)

  13. Doğal Bitki Antibiyotiği: Resveratrol

    OpenAIRE

    Alkan, Rezan

    2007-01-01

    Phytoalexins are low molecular weight secondary metabolites made by plants as a defense response to microbial infections, wounding and UV radiation. Resveratrol (trans-3, 4', 5-trihydroxystilbene), is a phytoalexin found in at least 72 species of plants distributed among 31 genera and 12 families. It is a naturally occurring antioxidant found in grapes, grape products such as red wine and some other botanical sources like peanuts and peanut butter, pistachio, dark chocolate and cocoa li...

  14. Resveratrol Reverses Functional Chagas Heart Disease in Mice

    Science.gov (United States)

    Mata-Santos, Hilton; Vicentino, Amanda R. R.; Feijó, Daniel F.; Meyer-Fernandes, José R.; Paula-Neto, Heitor A.; Medei, Emiliano; Bozza, Marcelo T.; Lannes-Vieira, Joseli; Paiva, Claudia N.

    2016-01-01

    Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol’s actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC. PMID:27788262

  15. Resveratrol and Endothelial Nitric Oxide

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    Ning Xia

    2014-10-01

    Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

  16. Strategies for enhancing resveratrol production and the expression of pathway enzymes.

    Science.gov (United States)

    Lu, Yao; Shao, Dongyan; Shi, Junling; Huang, Qingsheng; Yang, Hui; Jin, Mingliang

    2016-09-01

    Trans-resveratrol (trans-3,5,4'-trihydroxystilbene) is one of the most promising stilbenes, a type of natural phenol that is produced naturally by some plant species in response to stress. Resveratrol exhibits multiple bioactivities and is used in the agriculture, medical, food, and cosmetic industries due to its antitumor, anti-inflammatory, cardioprotective, and antioxidant properties. Due to the increasing demand, an active area of investigation is the use of plant cell culture and metabolic engineering techniques to produce large quantities of active resveratrol. However, most recent studies have focused on the efficiency of synthesizing resveratrol in vitro, but have not investigated the contributions of the transcriptional activities of the genes encoding the related enzymes in the biosynthesis pathway. This article reviews recently developed methods for the biosynthesis of resveratrol and comprehensively reviews the current state of knowledge of the function of the key pathway enzymes in resveratrol synthesis. Approaches for enhancing resveratrol production, such as introducing non-pathway genes and co-localizing enzymes are described in detail. PMID:27405437

  17. Anti-Inflammatory and Organ-Protective Effects of Resveratrol in Trauma-Hemorrhagic Injury

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    Fu-Chao Liu

    2015-01-01

    Full Text Available Resveratrol, a natural polyphenolic compound of grape and red wine, owns potential anti-inflammatory effects, which results in the reduction of cytokines overproduction, the inhibition of neutrophil activity, and the alteration of adhesion molecules expression. Resveratrol also possesses antioxidant, anti-coagulation and anti-aging properties, and it may control of cell cycle and apoptosis. Resveratrol has been shown to reduce organ damage following traumatic and shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the activation of estrogen receptor, the regulation of the sirtuin 1/nuclear factor-kappa B and mitogen-activated protein kinases/hemeoxygenase-1 pathway, and the mediation of proinflammatory cytokines and reactive oxygen species formation and reaction. In the recent studies, resveratrol attenuates hepatocyte injury and improves cardiac contractility due to reduction of proinflammatory mediator expression and ameliorates hypoxia-induced liver and kidney mitochondrial dysfunction following trauma and hemorrhagic injuries. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to protect organ function in trauma-hemorrhagic injury. In this review, the organ-protective and anti-inflammatory effects of resveratrol in trauma-hemorrhagic injury will be discussed.

  18. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells.

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    Qinghe Chen

    apoptosis, and inhibition of cyclin D1 by resveratrol. CONCLUSION/SIGNIFICANCE: These data suggest that FOXO transcription factors mediate anti-proliferative and pro-apoptotic effects of resveratrol, in part due to activation of extrinsic apoptosis pathway.

  19. Dihydro-resveratrol-A potent dietary polyphenol

    Energy Technology Data Exchange (ETDEWEB)

    Gakh, Andrei A [ORNL; Anisimova, Natalia Yu [N.N. Blokhin Russian Cancer Research Center; Kiselevsky, Mikhail V [N.N. Blokhin Russian Cancer Research Center; Sadovnikov, Sergey V [Hefei National Laboratory for the Physical Sciences at Microscale; Stankov, Ivan N [Chemical Diversity Research Institute; Yudin, Mikhail V [Chemical Diversity Research Institute; Rufanov, Konstantin A [Chemical Diversity Research Institute; Krasavin, Mikhail Yu [Chemical Diversity Research Institute; Sosnov, Andrey V [Chemical Diversity Research Institute

    2010-01-01

    Dihydro-resveratrol (dihydro-R), a prominent polyphenol component of red wine, has a profound proliferative effect on hormone-sensitive tumor cell lines such as breast cancer cell line MCF7. We found a significant increase in MCF7 tumor cells growth rates in the presence of picomolar concentrations of this compound. The proliferative effect of dihydro-R was not observed in cell lines that do not express hormone receptors (MDA-MB-231, BT-474, and -562).

  20. Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Mizutani, K; Ikeda, K; Kawai, Y; Yamori, Y

    2000-04-01

    We examined the effect of resveratrol (3,4',5-trihydroxy stilbene), a phenolic compound found in the skins of most grapes, on blood pressure and bone loss in ovariectomized (OVX), stroke-prone spontaneously hypertensive rats (SHRSP). Nineteen-week-old female SHRSP were divided into a sham-ovariectomized (sham) group fed a control diet and two OVX groups fed either a control diet (OVX-Cont) or a diet supplemented with resveratrol (5 mg/kg per d; OVX-Resv). Ovariectomy induced significant increases in systolic blood pressure (SBP). Resveratrol lowered the SBP by 15%) by the third week of administration, and this effect was maintained throughout the study. Resveratrol treatment also significantly enhanced endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in OVX rats. Finally, femur breaking energies measured for the resveratrol-treated (OVX-Resv) group were significantly higher than those of the resveratrol-untreated (OVX-Cont) group. While no significant differences in calcium, magnesium and phosphorus content were found between the femurs of OVX-Cont and OVX-Resv rats, the femur hydroxyproline content in the OVX-Resv group was significantly higher than of the OVX-Cont group. We conclude that, in OVX-SHRSP, resveratrol acts by a similar mechanism to mammalian estrogens, lowering blood pressure by increasing dilatory responses to ACh. The present study also demonstrated that resveratrol was able to prevent ovariectomy-induced decreases in femoral bone strength.

  1. Regulation of Proliferation and Autophagy and Its Possible Mechanisms of Resveratrol on HepG2 Cells in Hypoxia%低氧条件下白藜芦醇对HePG2细胞增殖及自噬的调节作用及初步机制

    Institute of Scientific and Technical Information of China (English)

    严俊; 李晓姝; 孙慧燕; 王华; 肖凤君; 李庆芳; 杨月峰; 王立生; 吴祖泽

    2011-01-01

    Resveratrol as a polyphenolic compound is naturally enriched in grapes, red wine and peanuts. Resveratrol has been reported to have potent anticancer and antioxidant properties. Most studies about the anti-cancer effect of resveratrol have been described previously when cells on the normoxia. The effect of resveratrol in hypoxia, the environment which mimics the state of tumor in vivo remains unclear. In this study, human hepatocellular carcinoma HepG2 cells were used to understand the effects and the possible mechanisms by which resveratrol acts as an anticancer agent in hypoxic conditions (1% O2). Our data show that resveratrol significantly inhibits HepG2 cell viability in hypoxia, and promotes hypoxia stress induced autophagy as well. We also found that the NAD-dependent deacetylase (Sirtl) and sphingosine kinase 1 (SPK1) might be involved in the effects of resveratrol in hypoxia. Collectively, our studies reveal the possible mechanisms of insensitive effect of the resveratrol in hypoxia, and further clarify the anticancer effect of resveratrol on solid tumor cells, providing a reference for drug development of resveratrol.%白藜芦醇(resveratro1)是天然存在于葡萄、红酒及花生等中的一种多酚类化合物,具有抗癌、抗氧化等作用.目前针对resveratrol抗癌作用的研究大多侧重于常氧状态,而对于更接近体内肿瘤生长环境即低氧状态的研究相对匮乏.本文以肝癌细胞HepG2为模型,探讨了低氧(1%O2)条件下resveratrol抑癌的相关功能和机制.结果表明,在低氧状态下resveratrol不仅抑制HepG2细胞的活性,而且也促进了低氧诱导的自噬保护机制;进一步研究发现,去乙酰化酶Sirtl和鞘氨醇激酶SPK1也参与上述过程.本文初步揭示了低氧状态下癌细胞对resveratrol敏感性低的可能机制,更加明确resveratrol在实体瘤中的抗癌作用,并为resveratrol的药物研发提供了借鉴.

  2. Resveratrol differentially regulates NAMPT and SIRT1 in Hepatocarcinoma cells and primary human hepatocytes.

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    Susanne Schuster

    Full Text Available Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382. Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells.

  3. DNA damage is a late event in resveratrol-mediated inhibition of Escherichia coli.

    Science.gov (United States)

    Subramanian, Mahesh; Soundar, Swetha; Mangoli, Suhas

    2016-07-01

    Resveratrol is an important phytoalexin notable for a wide variety of beneficial activities. Resveratrol has been reported to be active against various pathogenic bacteria. However, it is not clear at the molecular level how this important activity is manifested. Resveratrol has been reported to bind to cupric ions and reduce it. In the process, it generates copper-peroxide complex and reactive oxygen species (ROS). Due to this ability, resveratrol has been shown to cleave plasmid DNA in several studies. To this end, we envisaged DNA damage to play a role in resveratrol mediated inhibition in Escherichia coli. We employed DNA damage repair deficient mutants from keio collection to demonstrate the hypersensitive phenotype upon resveratrol treatment. Analysis of integrity and PCR efficiency of plasmid DNA from resveratrol-treated cells revealed significant DNA damage after 6 h or more compared to DNA from vehicle-treated cells. RAPD-PCR was performed to demonstrate the damage in genomic DNA from resveratrol-treated cells. In addition, in situ DNA damage was observed under fluorescence microscopy after resveratrol treatment. Further resveratrol treatment resulted in cell cycle arrest of significant fraction of population revealed by flow cytometry. However, a robust induction was not observed in phage induction assay and induction of DNA damage response genes quantified by promoter fused fluorescent tracker protein. These observations along with our previous observation that resveratrol induces membrane damage in E. coli at early time point reveal, DNA damage is a late event, occurring after a few hours of treatment. PMID:27021971

  4. Resveratrol in Parts of Vine and Wine Originating from Bohemian and Moravian Vineyard Regions

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    Karel Melzoch

    2001-03-01

    Full Text Available Chemically, resveratrol is a substance of a polyphenolic character from the group of phytoalexins - 3,5,4´- trihydroxystilbene - and exists in cis and trans-isomer forms. In natural sources trans-isomer is more common. As a natural polyphenolic substance, it shows a whole range of biological activities, such as anti-oxidizing and anti-microbial features (namely anti-fungal activities, the ability to absorb free radicals, affects blood sedimentation rate etc. Recently, trans-resveratrol has also been attributed anti-mutagen and chemo-protective features against cancer proliferation. It is assumed that resveratrol could be one of the active substances contributing to the health benefits, namely it decreases the risk of cardiovascular diseases through a reasonable consumption of red wine. Grapes of Vitis vinifera and especially red wine represent its main source in human diet. Grape peels contain about 0.5 to 2.0 mg of resveratrol/g of dry weight and the average concentration in red wines of world provenience fluctuates between 1.0 and 3.0 mg/l. Resveratrol was determined by HPLC method with electrochemical detection after direct injection of wine or plant extracts. As expected, red wines from vines originating in the Bohemian and Moravian vineyard regions appeared to contain relatively high levels of resveratrol (from 1.3 to 15.4 mg/l and trans/cis ratio ranged from 0.5 to 4.8, excess of cis-resveratrol to trans-isomer was typical for red wine growing in Most region (northern Bohemia where vineyards are exposed to higher environmental stress due to frequent air pollutions in this area. In addition, resveratrol determined in different parts of grapevine (leaves, rachis varied from 6 to 490 mg/kg of the dry matter. Cluster stems were found as the richest source of resveratrol.

  5. Vibrational spectroscopy of resveratrol

    Science.gov (United States)

    Billes, Ferenc; Mohammed-Ziegler, Ildikó; Mikosch, Hans; Tyihák, Ernő

    2007-11-01

    In this article the authors deal with the experimental and theoretical interpretation of the vibrational spectra of trans-resveratrol (3,5,4'-trihydroxy- trans-stilbene) of diverse beneficial biological activity. Infrared and Raman spectra of the compound were recorded; density functional calculations were carried out resulting in the optimized geometry and several properties of the molecule. Based on the calculated force constants, a normal coordinate analysis yielded the character of the vibrational modes and the assignment of the measured spectral bands.

  6. Suppression of Ultraviolet B Exposure-Mediated Activation of NF-κB in Normal Human Keratinocytes by Resveratrol

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    Vaqar Mustafa Adhami

    2003-01-01

    Full Text Available Chemoprevention by naturally occurring agents is a newer dimension in the management of neoplasia, including skin cancer. Solar ultraviolet (UV radiation is the major cause of skin cancer. We recently demonstrated that resveratrol (3,5,4'-trihydroxystilbene, a polyphenolic antioxidant found in grapes and red wine, imparts protection from UVB-mediated cutaneous damages in SKH-1 hairless mice. The mechanism of action of resveratrol is not clearly understood. Here, we investigated the involvement of nuclear factor kappa B (NF-κB, which is known to play a critical role in skin biology and the development of skin cancer, as the mechanism of chemoprevention of UV damage by resveratrol. In the normal human epidermal keratinocytes, resveratrol blocked UVB-mediated (40 mJ/cm2 activation of NF-κB in a dose-dependent (5, 10, and 25μM resveratrol for 24 hours as well as time-dependent (5μ/M resveratrol for 12, 24, and 48 hours fashion. Resveratrol treatment of keratinocytes also inhibited UVB-mediated 1 phosphorylation and degradation of IκBα, and 2 activation of IKKα. We suggest that NF-κB pathway plays a critical role in the chemopreventive effects of resveratrol against the adverse effects of UV radiation including photocarcinogenesis.

  7. Suppressing effect of resveratrol on the migration and invasion of human metastatic lung and cervical cancer cells.

    Science.gov (United States)

    Kim, Yoon Suk; Sull, Jae Woong; Sung, Ho Joong

    2012-09-01

    The antioxidant 3,4',5 tri-hydroxystilbene (resveratrol), a phytoalexin found in grapes, shows cancer preventive activities, including inhibition of migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of resveratrol on tumor metastasis, especially in human metastatic lung and cervical cancers is not clear. A non-cytotoxic dosage of resveratrol causes a reduction in the generation of reactive oxygen species, and suppresses phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration in both A549 and HeLa cells. Resveratrol also decreases both the expression and the enzymatic activity of matrix metalloproteinase-9 (MMP-9), and the promoter activity of PMA-stimulated MMP-9 is also inhibited. However, resveratrol does not affect either the expression or the proteolytic activity of MMP-2. Our results also show that resveratrol suppresses the transcription of MMP-9 by the inhibition of both NF-κB and AP-1 transactivation. These results indicate that resveratrol inhibits both NF-κB and AP-1 mediated MMP-9 expression, leading to suppression of migration and invasion of human metastatic lung and cervical cancer cells. Resveratrol has potential for clinical use in preventing invasion by human metastatic lung and cervical cancers.

  8. Resveratrol-procyanidin blend: nutraceutical and antiaging efficacy evaluated in a placebo-controlled, double-blind study

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    Buonocore D

    2012-10-01

    treatment, values for systemic oxidative stress, plasmatic antioxidant capacity, and skin antioxidant power had increased significantly. Additionally, skin moisturization and elasticity had improved, while skin roughness and depth of wrinkles had diminished. Intensity of age spots had significantly decreased, as evidenced by improvement in the individual typological angle.Conclusion: Nutraceutical and pharmacological intervention with a supplement characterized by a specific blend of resveratrol and procyanidin may be a promising strategy to support treatments for the reduction of skin wrinkling, as well as reducing systemic and skin oxidative stress.Keywords: antiaging, nutraceuticals, procyanidin, resveratrol supplementation, skin

  9. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    Energy Technology Data Exchange (ETDEWEB)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald, E-mail: gerald.thiel@uks.eu

    2015-03-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified.

  10. Resveratrol products resulting by free radical attack

    Energy Technology Data Exchange (ETDEWEB)

    Bader, Yvonne; Quint, R.M. [Section Radiation Biology, Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, UZAII, Althanstrasse 14, A-1090 Vienna (Austria); Getoff, Nikola [Section Radiation Biology, Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, UZAII, Althanstrasse 14, A-1090 Vienna (Austria)], E-mail: nikola.getoff@univie.ac.at

    2008-06-15

    Trans-resveratrol (trans-3,4',5-trihydroxystilbene; RES), which is contained in red wine and many plants, is one of the most relevant and extensively investigated stilbenes with a broad spectrum of biological activities. Among other duties, RES has been reported to have anti-carcinogenetic activities, which could be attributed to its antioxidant properties. The degradation of RES was studied under various conditions. The products (aldehydes, carboxylic acids, etc.) generated from RES by the attack of free radicals were registered as a function of the radical concentration (absorbed radiation dose). Based on the obtained data it appears that the OH radicals are initiating the rather complicated process, which involves of the numerous consecutive reactions. A possible starting reaction mechanism is presented.

  11. Resveratrol products resulting by free radical attack

    Science.gov (United States)

    Bader, Yvonne; Quint, R. M.; Getoff, Nikola

    2008-06-01

    Trans-resveratrol ( trans-3,4',5-trihydroxystilbene; RES), which is contained in red wine and many plants, is one of the most relevant and extensively investigated stilbenes with a broad spectrum of biological activities. Among other duties, RES has been reported to have anti-carcinogenetic activities, which could be attributed to its antioxidant properties. The degradation of RES was studied under various conditions. The products (aldehydes, carboxylic acids, etc.) generated from RES by the attack of free radicals were registered as a function of the radical concentration (absorbed radiation dose). Based on the obtained data it appears that the OH radicals are initiating the rather complicated process, which involves of the numerous consecutive reactions. A possible starting reaction mechanism is presented.

  12. Glycosylation of resveratrol protects it from enzymic oxidation.

    Science.gov (United States)

    Regev-Shoshani, Gilly; Shoseyov, Oded; Bilkis, Itzhak; Kerem, Zohar

    2003-01-01

    Plant polyphenols, including dietary polyphenols such as resveratrol, are important components in the plant antioxidant and defence systems. They are also known to exert beneficial effects on human health through diet. As they are produced, these polyphenols may be subjected to deleterious enzymic oxidation by the plant polyphenol oxidases. They are generally synthesized as glycosides like 5,4'-dihydroxystilbene-3-O-beta-D-glucopyranoside, the 3-glucoside of resveratrol. The effects of the glycosylation and methylation of the parent resveratrol on its enzymic oxidation were studied. Methyl and glucosyl derivatives were synthesized using simple one-step methodologies. The kinetics of their enzymic oxidation by tyrosinases were defined. Substitution at the p-hydroxy group, by either glucose or methyl, abolished enzymic oxidation by both mushroom and grape tyrosinases. Substitution at the m-hydroxy group with methyl had a small effect, but substitution with glucose resulted in a much lower affinity of the enzymes for the glycoside. We suggest that glycosylation of polyphenols in nature helps to protect these vital molecules from enzymic oxidation, extending their half-life in the cell and maintaining their beneficial antioxidant capacity and biological properties. PMID:12697026

  13. Resveratrol Suppresses PAI-1 Gene Expression in a Human In Vitro Model of Inflamed Adipose Tissue

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    Ivana Zagotta

    2013-01-01

    Full Text Available Increased plasminogen activator inhibitor-1 (PAI-1 levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NFκB pathway. Together, resveratrol can act as NFκB inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.

  14. Sirt1 Is Required for Resveratrol-Mediated Chemopreventive Effects in Colorectal Cancer Cells

    Science.gov (United States)

    Buhrmann, Constanze; Shayan, Parviz; Popper, Bastian; Goel, Ajay; Shakibaei, Mehdi

    2016-01-01

    Sirt1 is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can serve both as a tumor promoter and suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via Sirt1 in CRC growth and metastasis remains unclear; which was the subject of this study. We found that resveratrol suppressed proliferation and invasion of two different human CRC cells in a dose-dependent manner, and interestingly, this was accompanied with a significant decrease in Ki-67 expression. By transient transfection of CRC cells with Sirt1-ASO, we demonstrated that the anti-tumor effects of resveratrol on cells was abolished, suggesting the essential role of this enzyme in the resveratrol signaling pathway. Moreover, resveratrol downregulated nuclear localization of NF-κB, NF-κB phosphorylation and its acetylation, causing attenuation of NF-κB-regulated gene products (MMP-9, CXCR4) involved in tumor-invasion and metastasis. Finally, Sirt1 was found to interact directly with NF-κB, and resveratrol did not suppress Sirt1-ASO-induced NF-κB phosphorylation, acetylation and NF-κB-regulated gene products. Overall, our results demonstrate that resveratrol can suppress tumorigenesis, at least in part by targeting Sirt1 and suppression of NF-κB activation. PMID:26959057

  15. Potentiation of resveratrol-induced apoptosis by matrine in human hepatoma HepG2 cells.

    Science.gov (United States)

    Ou, Xiuyuan; Chen, Yan; Cheng, Xinxin; Zhang, Xumeng; He, Qiyang

    2014-12-01

    Resveratrol, a natural polyphenolic phytochemical, has received considerable attention due to its potential chemopreventive and chemotherapeutic properties. In the present study, we first evaluated the growth-inhibitory effect of resveratrol on HepG2 cells and explored the underlying molecular mechanisms. Resveratrol inhibited proliferation and induced apoptosis in HepG2 cells via activation of caspase-9 and caspase-3, upregulation of the Bax/Bcl-2 ratio and induction of p53 expression. Cell cycle analysis demonstrated that resveratrol arrested cell cycle progression in the G1 and S phase. We further focused on the combination of matrine, a natural component extracted from the traditional Chinese medical herb Sophora flavescens Ait., as a mechanism to potentiate the growth-inhibitory effect of resveratrol on HepG2 cells. Both MTT and colony formation assay results indicated that the combined treatment of resveratrol and matrine exhibited a synergistic antiproliferative effect. In addition, resveratrol-induced apoptosis was significantly enhanced by matrine, which could be attributed to activation of caspase-3 and caspase-9, downregulation of survivin, induction of reactive oxygen species (ROS) generation and disruption of mitochondria membrane potential (Δψm). Our findings suggest that the combination treatment of resveratrol and matrine is a promising novel anticancer strategy for liver cancer; it also provides new insights into the mechanisms of combined therapy.

  16. Sirt1 Is Required for Resveratrol-Mediated Chemopreventive Effects in Colorectal Cancer Cells.

    Science.gov (United States)

    Buhrmann, Constanze; Shayan, Parviz; Popper, Bastian; Goel, Ajay; Shakibaei, Mehdi

    2016-03-05

    Sirt1 is a NAD⁺-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can serve both as a tumor promoter and suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via Sirt1 in CRC growth and metastasis remains unclear; which was the subject of this study. We found that resveratrol suppressed proliferation and invasion of two different human CRC cells in a dose-dependent manner, and interestingly, this was accompanied with a significant decrease in Ki-67 expression. By transient transfection of CRC cells with Sirt1-ASO, we demonstrated that the anti-tumor effects of resveratrol on cells was abolished, suggesting the essential role of this enzyme in the resveratrol signaling pathway. Moreover, resveratrol downregulated nuclear localization of NF-κB, NF-κB phosphorylation and its acetylation, causing attenuation of NF-κB-regulated gene products (MMP-9, CXCR4) involved in tumor-invasion and metastasis. Finally, Sirt1 was found to interact directly with NF-κB, and resveratrol did not suppress Sirt1-ASO-induced NF-κB phosphorylation, acetylation and NF-κB-regulated gene products. Overall, our results demonstrate that resveratrol can suppress tumorigenesis, at least in part by targeting Sirt1 and suppression of NF-κB activation.

  17. Sirt1 Is Required for Resveratrol-Mediated Chemopreventive Effects in Colorectal Cancer Cells

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    Constanze Buhrmann

    2016-03-01

    Full Text Available Sirt1 is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can serve both as a tumor promoter and suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via Sirt1 in CRC growth and metastasis remains unclear; which was the subject of this study. We found that resveratrol suppressed proliferation and invasion of two different human CRC cells in a dose-dependent manner, and interestingly, this was accompanied with a significant decrease in Ki-67 expression. By transient transfection of CRC cells with Sirt1-ASO, we demonstrated that the anti-tumor effects of resveratrol on cells was abolished, suggesting the essential role of this enzyme in the resveratrol signaling pathway. Moreover, resveratrol downregulated nuclear localization of NF-κB, NF-κB phosphorylation and its acetylation, causing attenuation of NF-κB-regulated gene products (MMP-9, CXCR4 involved in tumor-invasion and metastasis. Finally, Sirt1 was found to interact directly with NF-κB, and resveratrol did not suppress Sirt1-ASO-induced NF-κB phosphorylation, acetylation and NF-κB-regulated gene products. Overall, our results demonstrate that resveratrol can suppress tumorigenesis, at least in part by targeting Sirt1 and suppression of NF-κB activation.

  18. Antioxidant cosmeto-textiles: skin assessment.

    Science.gov (United States)

    Alonso, Cristina; Martí, Meritxell; Martínez, Vanessa; Rubio, Laia; Parra, José L; Coderch, Luisa

    2013-05-01

    Resveratrol, a natural product, has been reported to have antioxidant activities such as the scavenging of free radicals. This compound could be used in the dermocosmetic field to protect the skin from oxidative stress. In this work, the percutaneous profile of resveratrol in ethanol solutions through pig skin was determinated by an in vitro methodology. The percutaneous absorption of resveratrol was measured and compared with trolox, an analogous of Vitamin E. Both antioxidants were found in all skin sections (stratum corneum, epidermis, and dermis). Besides, the free radical scavenging activity of resveratrol and trolox has been evaluated using DPPH method. The effective dose (ED₅₀) of compounds and DPPH radical inhibition in each skin layer were evaluated. Under the conditions used for these experiments, it can be deduced that resveratrol is more efficient than trolox as an antioxidant, also in the inner skin layers. The cosmeto-textiles with an active substance incorporated into their structure are increasingly used in the cosmetics and pharmaceutical industries. The action of several cosmeto-textiles on the skin was assessed by in vitro and in vivo methodologies. Samples of these cosmeto-textiles were prepared with resveratrol incorporated into cotton and polyamide fabrics. An in vitro percutaneous absorption was used to demonstrate the delivery of the resveratrol from the textile to the different skin layers (stratum corneum, epidermis, and dermis). Additionally, these cosmeto-textiles containing the antioxidant were applied onto the forearms of volunteers to evaluate the textiles' efficacy in skin penetration. The antioxidant's antiradical capacity was evaluated using the DPPH method. Results showed that resveratrol could be detected in the dermis, epidermis, and stratum corneum (SC) by an in vitro percutaneous absorption method and was also detected in the outermost layers of the SC by an in vivo method (stripping). A smaller amount of resveratrol was

  19. Resveratrol inhibits the expression of SREBP1 in cell model of steatosis via Sirt1-FOXO1 signaling pathway.

    Science.gov (United States)

    Wang, Guang-Li; Fu, Yu-Cai; Xu, Wen-Can; Feng, Ya-Qing; Fang, Shi-Rong; Zhou, Xiao-Hui

    2009-03-13

    Recent studies in mice have shown that resveratrol can protect the liver from fat accumulation induced by high fat diet. However, the exact mechanism is largely unknown. To explore the possible mechanism, we investigated the anti-lipogenic effect of resveratrol in vitro model. Oil Red O staining revealed that resveratrol could significantly ameliorate the excessive triglyceride accumulation in HepG2 cells induced by palmitate. The results of RT-PCR and Western blotting showed that resveratrol upregulated the expression of Sirt1 and forkhead box O1 (FOXO1), whereas downregulated the expression of sterol regulatory element binding protein1 (SREBP1). Moreover, resveratrol was shown to inhibit the activity of SREBP1, as evaluated by immunofluorescence assay. Our results suggest that resveratrol may attenuate fat deposition by inhibiting SREBP1 expression via Sirt1-FOXO1 pathway and thus may have application for the treatment of NAFLD. PMID:19285015

  20. LC-MS Guided Isolation of Bioactive Principles from Iris hookeriana and Bioevaluation of Isolates for Antimicrobial and Antioxidant Activities.

    Science.gov (United States)

    Dar, B A; Lone, S H; Shah, W A; Bhat, K A

    2016-08-01

    The genus Iris is diverse both in the abundance of secondary metabolities as well as the biological activities. The rhizomes of Iris hookeriana exhibit significant anthelminthic activity against gastrointestinal nematodes of sheep. Although Iris hookeriana has been a subject of the study of so many phytochemical studies, yet we report some constituents for the first time from this plant using a different isolation approach. This manuscript presents the isolation, antimicrobial and antioxidant evaluation of bioactive principles from Iris hookeriana. LC-MS guided isolation technique was applied for the separation of target constituents. The isolates were characterised by spectral techniques and subjected to antioxidant evaluation by DPPH assay. Four compounds; resveratrol, resveratroloside, junipeginin C and isorhamnetin-3-O-neohesperidoside were isolated for the first time along with 3 known compounds viz piceid, irigenin and iridin from I. hookeriana using this approach. The antioxidant activity screening of the isolates revealed that all the 4 constituents isolated for the first time, have strong antioxidant potential with IC50 of 14.0 µg/ml (resveratroloside), 19.7 µg/ml (junipeginen C), 12.8 µg/ml (resveratrol) and 19.8 µg/ml (isorhamnetin-3-O-neohesperodoside). So it can be safely concluded that LC-MS guided isolation of chemical compounds from Iris hookeriana has furnished 4 antioxidant constituents. Thus Iris hookeriana can act as as a good source of wonder molecule resveratrol and its 2 glycosides, resveratrolside and piceid which upon hydrolysis can be converted into the parent drug resveratrol. PMID:27281447

  1. 正常培养的人类前列腺癌细胞对白藜芦醇的吸收及白藜芦醇对靶向蛋白醌还原酶2QR2的作用%Uptake of resveratrol and role of resveratrol-targeting protein, quinone reductase 2, in normally cultured human prostate cells

    Institute of Scientific and Technical Information of China (English)

    Tze-Chen Hsieh

    2009-01-01

    Resveratrol is a dietary polyphenol espoused to have chemopreventive activity against a variety of human cancer types. We first reported that resveratrol significantly decreases the proliferation of both androgen-dependent and hormone-refractory prostate cancer cells. However, the effects of resveratrol in normal prostate epithelial and stromal cells, particularly with regard to its uptake, subcellular distribution and intracellular targets, have not been investigated. To advance the knowledge on accessibility and cellular disposition of resveratrol in prostate cells, [3H] resveratrol, fractionation of cell extracts into subcellular compartments, Western blot analysis, resveratrol affinity column chromatography and flow cytometry were used to study the uptake and intracellular distribution of resveratrol in normally cultured prostate stromal (PrSCs) and epithelial cells (PrECs). Pretreatment of both PrSCs and PrECs for 2 days with resveratrol modulated its uptake and selectively increased its distribution to the membrane and organelle compartments. Resveratrol affinity column chromatography studies showed differential expression of a previously identified resveratrol-targeting protein, quinone reductase 2 (QR2), in PrSCs and PrECs. Flow cytometric analysis comparing resveratrol-treated and untreated PrSCs showed a large decrease in G1-phase and a concomitant increase in S and G2/M-phases of the cell cycle. These results suggest that resveratrol suppresses PrSC proliferation by affecting cell cycle phase distribution, which may involve the participation by QR2.

  2. Improving effect of chronic resveratrol treatment on central monoamine synthesis and cognition in aged rats.

    Science.gov (United States)

    Sarubbo, F; Ramis, M R; Aparicio, S; Ruiz, L; Esteban, S; Miralles, A; Moranta, D

    2015-06-01

    Resveratrol is a polyphenol exhibiting antioxidant and neuroprotective effects in neurodegenerative diseases. However, neuroprotective properties during normal aging have not been clearly demonstrated. We analyzed the in vivo effects of chronic administration of resveratrol (20 mg/kg/day for 4 weeks) in old male rats (Wistar, 20 months), on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities which mediate central monoaminergic neurotransmitters synthesis, and besides, on hippocampal-dependent working memory test (radial maze). Our results show an age-related decline in neurochemical parameters that were reversed by resveratrol administration. The resveratrol treatment enhances serotonin (5-HT) levels in pineal gland, in hippocampus, and in striatum, and those of noradrenaline (NA) in hippocampus and also dopamine (DA) in striatum. These changes were largely due to an increased activity of TPH-1 (463 % in pineal gland), TPH-2 (70-51 % in hippocampus and striatum), and TH (150-36 % in hippocampus and striatum). Additionally, the observed hippocampal effects correlate with a resveratrol-induced restorative effect on working memory (radial maze). In conclusion, this study suggests resveratrol treatment as a restoring therapy for the impaired cognitive functions occurring along normal aging process, by preventing 5-HT, DA, and NA neurotransmission decline.

  3. Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway

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    Jing Zhang

    2015-01-01

    Full Text Available Resveratrol, herbal nonflavonoid polyphenolic compound naturally derived from grapes, has long been acknowledged to possess extensive biological and pharmacological properties including antioxidant and anti-inflammatory ones and may exert a neuroprotective effect on neuronal damage in neurodegenerative diseases. However, the underlying molecular mechanisms remain undefined. In the present study, we intended to investigate the neuroprotective effects of resveratrol against 6-OHDA-induced neurotoxicity of PC12 cells and further explore the possible mechanisms involved. For this purpose, PC12 cells were exposed to 6-OHDA in the presence of resveratrol (0, 12.5, 25, and 50 μM. The results showed that resveratrol increased cell viability, alleviated the MMP reduction, and reduced the number of apoptotic cells as measured by MTT assay, JC-1 staining, and Hoechst/PI double staining (all p<0.01. Immunofluorescent staining and Western blotting revealed that resveratrol averts 6-OHDA induced CXCR4 upregulation (p<0.01. Our results demonstrated that resveratrol could effectively protect PC12 cells from 6-OHDA-induced oxidative stress and apoptosis via CXCR4 signaling pathway.

  4. Resveratrol-induced augmentation of telomerase activity delays senescence of endothelial progenitor cells

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-bin; ZHU Li; HUANG Jun; YIN Yi-gang; KONG Xiang-qing; RONG Qi-fei; SHI Ai-wu; CAO Ke-jiang

    2011-01-01

    Background Previous studies have shown that resveratrol increases endothelial progenitor cell (EPC) numbers and functional activity.Increased EPC numbers and activity are associated with the inhibition of EPC senescence.In this study,we investigated the effect of resveratrol on the senescence of EPCs,leading to potentiation of cellular function.Methods EPCs were isolated from human peripheral blood and identified immunocytochemically.EPCs were incubated with resveratrol (1,10,and 50 μmol/L) or control for specified times.After in vitro cultivation,acidic β-galactosidase staining revealed the extent of senescence in the cells.To gain further insight into the underlying mechanism of the effect of resveratrol,we measured telomerase activity using a polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA) technique.Furthermore,we measured the expression of human telomerase reverse transcriptase (hTERT) and the phosphorylation of Akt by immunoblotting.Results Resveratrol dose-dependently inhibited the onset of EPC senescence in culture.Resveratrol also significantly increased telomerase activity.Interestingly,quantitative real-time PCR analysis demonstrated that resveratrol dose-dependently increased the expression of the catalytic subunit,hTERT,an effect that was significantly inhibited by pharmacological phosphatidylinositol 3-kinase (PI3-K) blockers (wortmannin).The expression of hTERT is regulated by the PI3-K/Akt pathway; therefore,we examined the effect of resveratrol on Akt activity in EPCs.Immunoblotting analysis revealed that resveratrol led to dose-dependent phosphorylation and activation of Akt in EPCs.Conclusion Resveratrol delayed EPCs senescence in vitro,which may be dependent on telomerase activation.

  5. Effect of resveratrol and beta-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells.

    Science.gov (United States)

    Awad, Atif B; Burr, Andrew T; Fink, Carol S

    2005-03-01

    The objective of this project was to identify some possible mechanisms by which two common phytochemicals, resveratrol and beta-sitosterol, inhibit the growth of human prostate cancer PC-3 cells. These mechanisms include the effect of the phytochemicals on apoptosis, cell cycle progression, prostaglandin synthesis and the production of reactive oxygen species (ROS). Prostaglandins have been known to play a role in regulating cell growth and apoptosis. PC-3 cells were supplemented with 50 microM resveratrol or 16 microM beta-sitosterol alone or in combination for up to 5 days. Phytochemical supplementation resulted in inhibition in cell growth. beta-Sitosterol was more potent than resveratrol and the combination of the two resulted in greater inhibition than supplementation with either alone. Long-term supplementation with resveratrol or beta-sitosterol elevated basal prostaglandin release but beta-sitosterol was much more potent than resveratrol in this regard. beta-Sitosterol was more effective than resveratrol in inducing apoptosis and the combination had an intermediate effect after 1 day of supplementation. Cells supplemented with resveratrol were arrested at the G1 phase and at the G2/M phase in the case of beta-sitosterol while the combination resulted in cell arrest at the two phases of the cell cycle. beta-Sitosterol increased ROS production while resveratrol decreased ROS production. The combination of the two phytochemicals resulted in an intermediate level of ROS. The observed changes in prostaglandin levels and ROS production by these two phytochemicals may suggest their mediation in the growth inhibition. The reduction in ROS level and increase by resveratrol supplementation in PC-3 cells reflects the antioxidant properties of resveratrol. It was concluded that these phytochemicals may induce the inhibition of tumor growth by stimulating apoptosis and arresting cells at different locations in the cell cycle and the mechanism may involve alterations in

  6. Effects of resveratrol on membrane biophysical properties: relevance for its pharmacological effects.

    Science.gov (United States)

    Brittes, J; Lúcio, M; Nunes, C; Lima, J L F C; Reis, S

    2010-11-01

    The current study gathers a range of spectrophotometric and spectrofluorimetric techniques to systematically monitor the effects of resveratrol (trans-3,5,4'-trihydrostilbene) on the biophysical properties of membrane model systems consisting of unilamellar liposomes of phosphatidylcholine (DPPC) with the ultimate goal of relating these effects with some of the well documented pharmacological properties of this compound, and clarifying some controversial results reported on the literature. Physiological conditions have been pursued, such as a buffered pH control with adjusted ionic strength similar to the blood plasma conditions (pH 7.4, I=0.1M) and the study at different membrane physical states (gel phase and fluid phase) for the assessment of resveratrol-membrane: aqueous partition coefficient by derivative spectroscopy. Results obtained by fluorescence quenching and anisotropy studies indicate that resveratrol has a membrane fluidizing effect and is able to permeate the membrane even in the gel phase. These results mirror the well described antioxidant effect of resveratrol, since antioxidants have to reach peroxidised rigid membranes and increase membrane fluidity in order to interact more efficiently with lipid radicals in the disordered lipid bilayer. Location of resveratrol pointed also to a membrane distribution that is favourable for scavenging the lipid radicals and was elucidated using probes positioned at different membrane depths suggesting that this compound penetrates into the acyl membrane region but also positions its polar hydroxyl group near the headgroup region of the membrane. PMID:20691168

  7. Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors.

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    Sanjit K Roy

    Full Text Available BACKGROUND: The forkhead transcription factors of the O class (FOXO play a direct role in cellular proliferation, oxidative stress response, and tumorigenesis. The objectives of this study were to examine whether FOXOs regulate antitumor activities of resveratrol in pancreatic cancer cells in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Pancreatic cancer cell lines were treated with resveratrol. Cell viability, colony formation, apoptosis and cell cycle were measured by XTT, soft agar, TUNEL and flow cytometry assays, respectively. FOXO nuclear translocation, DNA binding and transcriptional activities were measured by fluorescence technique, gelshift and luciferase assay, respectively. Mice were orthotopically implanted with PANC1 cells and orally gavaged with resveratrol. The components of PI3K and ERK pathways, FOXOs and their target gene expressions were measured by the Western blot analysis. Resveratrol inhibited cell viability and colony formations, and induced apoptosis through caspase-3 activation in four pancreatic cancer cell lines (PANC-1, MIA PaCa-2, Hs766T, and AsPC-1. Resveratrol induced cell cycle arrest by up-regulating the expression of p21/CIP1, p27/KIP1 and inhibiting the expression of cyclin D1. Resveratrol induced apoptosis by up-regulating Bim and activating caspase-3. Resveratrol inhibited phosphorylation of FOXOs, and enhanced their nuclear translocation, FOXO-DNA binding and transcriptional activities. The inhibition of PI3K/AKT and MEK/ERK pathways induced FOXO transcriptional activity and apoptosis. Furthermore, deletion of FOXO genes abrogated resveratrol-induced cell cycle arrest and apoptosis. Finally, resveratrol-treated mice showed significant inhibition in tumor growth which was associated with reduced phosphorylation of ERK, PI3K, AKT, FOXO1 and FOXO3a, and induction of apoptosis and FOXO target genes. CONCLUSIONS: These data suggest that inhibition of ERK and AKT pathways act together to activate FOXO

  8. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus

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    Rachel H.X. Wong

    2016-07-01

    Full Text Available Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM. We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli, cognitive performance and correlations with plasma resveratrol concentrations. Methods: Thirty-six T2DM adults aged 40–80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. Results: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. Conclusion: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted.

  9. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Wong, Rachel H.X.; Raederstorff, Daniel; Howe, Peter R.C.

    2016-01-01

    Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR) to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli), cognitive performance and correlations with plasma resveratrol concentrations. Methods: Thirty-six T2DM adults aged 40–80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV) during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task) and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. Results: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. Conclusion: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted. PMID:27420093

  10. Differential gene expression in liver tissues of streptozotocin-induced diabetic rats in response to resveratrol treatment.

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    Gökhan Sadi

    Full Text Available This study was conducted to elucidate the genome-wide gene expression profile in streptozotocin induced diabetic rat liver tissues in response to resveratrol treatment and to establish differentially expressed transcription regulation networks with microarray technology. In addition to measure the expression levels of several antioxidant and detoxification genes, real-time quantitative polymerase chain reaction (qRT-PCR was also used to verify the microarray results. Moreover, gene and protein expressions as well as enzymatic activities of main antioxidant enzymes; superoxide dismutase (SOD-1 and SOD-2 and glutathione S-transferase (GST-Mu were analyzed. Diabetes altered 273 genes significantly and 90 of which were categorized functionally which suggested that genes in cellular catalytic activities, oxidation-reduction reactions, co-enzyme binding and terpenoid biosynthesis were dominated by up-regulated expression in diabetes. Whereas; genes responsible from cellular carbohydrate metabolism, regulation of transcription, cell signal transduction, calcium independent cell-to-cell adhesion and lipid catabolism were down-regulated. Resveratrol increased the expression of 186 and decreased the expression of 494 genes in control groups. While cellular and extracellular components, positive regulation of biological processes, biological response to stress and biotic stimulants, and immune response genes were up-regulated, genes responsible from proteins present in nucleus and nucleolus were mainly down-regulated. The enzyme assays showed a significant decrease in diabetic SOD-1 and GST-Mu activities. The qRT-PCR and Western-blot results demonstrated that decrease in activity is regulated at gene expression level as both mRNA and protein expressions were also suppressed. Resveratrol treatment normalized the GST activities towards the control values reflecting a post-translational effect. As a conclusion, global gene expression in the liver tissues is

  11. Identification and bioactivities of resveratrol oligomers and flavonoids from Carex folliculata seeds.

    Science.gov (United States)

    Li, Liya; Henry, Geneive E; Seeram, Navindra P

    2009-08-26

    Plants of the Carex genus (Family: Cyperaceae) have attracted recent attention as potential food additives because they contain high levels of bioactive polyphenols commonly found in plant foods. Seven compounds, which included two resveratrol oligomers and five flavonoids, were isolated from seeds of Carex folliculata L. (northern long sedge), a forage prevalent in the northern United States. The compounds were identified by (1)H and (13)C nuclear magnetic resonance and mass spectrometry data. The resveratrol oligomers were pallidol (1), a resveratrol dimer reported to be present in levels equivalent to those of resveratrol in red wine, and kobophenol A (2), a resveratrol tetramer with a unique 2,3,4,5-tetraaryltetrahydrofuran skeleton. The flavonoids were isoorientin (3), luteolin (4), quercetin (5), 3-O-methylquercetin (6), and rutin (7). Compounds were evaluated for antioxidant activity in the diphenylpicrylhydrazyl (DPPH) radical scavenging assay; cytotoxicity activity against human colon (HCT116, HT29) and breast (MCF7, MDA-MB-231) tumor cell lines; and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The antioxidant activities of the flavonoids (3-7; IC(50) values ranging from 50 to 200 microM) were comparable to that of ascorbic acid (IC(50) = 60 microM) and superior to those of the resveratrol derivatives (1 and 2; IC(50) > 1000 microM) and butylated hydroxytoluene (BHT; IC(50) = 1500 microM), a commercial antioxidant. In the cytotoxicity and antibacterial bioassays, compounds 4 (IC(50) for HCT116 = 45 microM) and 6 (IC(50) for MRSA = 6.4 microM) were the most active, respectively. Therefore, given the wide availability and underutilization of C. folliculata, this forage may provide a source of bioactive compounds useful for nutraceutical purposes. Also, this is the first reported phytochemical investigation of C. folliculata.

  12. Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts

    International Nuclear Information System (INIS)

    Epidemiologic studies suggest that low to moderate consumption of red wine is inversely associated with the risk of coronary heart disease; the protection is in part attributed to grape-derived polyphenols, notably trans-resveratrol, present in red wine. It is not clear whether the cardioprotective effects of resveratrol can be reproduced by standardized grape extracts (SGE). In the present studies, we determined, using cultured human aortic smooth muscle cells (HASMC), growth and specific gene responses to resveratrol and SGE provided by the California Table Grape Commission. Suppression of HASMC proliferation by resveratrol was accompanied by a dose-dependent increase in the expression of tumor suppressor gene p53 and heat shock protein HSP27. Using resveratrol affinity chromatography and biochemical fractionation procedures, we showed by immunoblot analysis that treatment of HASMC with resveratrol increased the expression of quinone reductase I and II, and also altered their subcellular distribution. Growth of HASMC was significantly inhibited by 70% ethanolic SGE; however, gene expression patterns in various cellular compartments elicited in response to SGE were substantially different from those observed in resveratrol-treated cells. Further, SGE also differed from resveratrol in not being able to induce relaxation of rat carotid arterial rings. These results indicate that distinct mechanisms are involved in the regulation of HASMC growth and gene expression by SGE and resveratrol

  13. Effect of Antioxidants Supplementation on Aging and Longevity

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    Izabela Sadowska-Bartosz

    2014-01-01

    Full Text Available If aging is due to or contributed by free radical reactions, as postulated by the free radical theory of aging, lifespan of organisms should be extended by administration of exogenous antioxidants. This paper reviews data on model organisms concerning the effects of exogenous antioxidants (antioxidant vitamins, lipoic acid, coenzyme Q, melatonin, resveratrol, curcumin, other polyphenols, and synthetic antioxidants including antioxidant nanoparticles on the lifespan of model organisms. Mechanisms of effects of antioxidants, often due to indirect antioxidant action or to action not related to the antioxidant properties of the compounds administered, are discussed. The legitimacy of antioxidant supplementation in human is considered.

  14. Resveratrol pretreatment attenuates injury and promotes proliferation of neural stem cells following oxygen-glucose deprivation/reoxygenation by upregulating the expression of Nrf2, HO-1 and NQO1 in vitro.

    Science.gov (United States)

    Shen, Changbo; Cheng, Wei; Yu, Pingping; Wang, Li; Zhou, Lulin; Zeng, Li; Yang, Qin

    2016-10-01

    There is considerable interest in the use of drugs and other methods for protecting implanted neural stem cells (NSCs) from the adverse environment of injured tissue for successful cell therapy. Resveratrol can modify cardiac stem cells to enhance their survival and differentiation, however, its effect and the mechanism underlying its neuroprotective effect on NSCs following stroke remain to be fully elucidated. Nuclear factor erythroid 2‑related factor 2 (Nrf‑2) signaling is important in antioxidative stress, and the role of Nrf‑2 signaling in the enhanced neuroprotection of NSCs by resveratrol following stroke also remains to be elucidated. In the present study, NSCs were pretreated with resveratrol prior to oxygen‑glucose deprivation/reoxygenation (OGD/R) in vitro. The survival, apoptosis and proliferation of the NSCs were assessed using an MTT assay, Hoechst 33258 staining of nuclei and flow cytometry, respectively. In addition, the activity of superoxide dismutase (SOD), level of malondiadehyde (MDA) and content of glutathione (GSH) were determined. The protein expressions levels of Nrf‑2, NAD(P)H:quinone oxidoreductase 1 (NQO‑1), and heme oxygenase 1 (HO‑1) were detected using western blot analysis. It was found that resveratrol markedly enhanced NSC survival and proliferation, decreased apoptosis and the levels of MDA, and increased the activity of SOD and content of GSH in a concentration‑dependent manner following OGD/R injury in vitro. In addition, the protein expression levels of Nrf2, HO‑1 and NQO1 were significantly upregulated. These findings suggested that resveratrol attenuated injury and promoted proliferation of the NSCs, at least in part, by upregulating the expression of Nrf2, HO‑1 and NQO1 following OGD/R injury in vitro. PMID:27573874

  15. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

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    J. Gambini

    2015-01-01

    Full Text Available Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol.

  16. Post-Harvest Induced Production of Salvianolic Acids and Significant Promotion of Antioxidant Properties in Roots of Salvia miltiorrhiza (Danshen

    Directory of Open Access Journals (Sweden)

    Guo-Jun Zhou

    2014-05-01

    Full Text Available Danshen, the dried roots of Salvia miltiorrhiza, is an extremely valued Traditional Chinese Medicine. Previously, we have demonstrated that salvianolic acid B (SaB, the important bioactive ingredient in this herb, was a post-harvest product. Here, we further reported that all salvianolic acids (SAs in the roots were post-harvest products of the drying process. In addition, the results of various radical scavenging activity assays, including lipid peroxidation (1, DPPH (2, hydroxyl (3 and superoxide (4, were significantly increased along with the accumulation of total salvianolic acids in the process. The contents of chemical targets and antioxidant activities both reached the highest value under thermal treatment at 130 °C for 80 min. In this dehydration period, contents of SaB, and sum of nine SAs increased from 0.01% to 5.51%, and 0.20% to 6.61%; and IC50 of antioxidant activity decreased from 4.85 to 2.69 (1; 7.75 to 0.43 (2; 2.57 to 1.13 (3 and 17.25 to 1.10 mg/mL. These results further supported the hypothesis that the newly harvested plant roots were still physiologically active and the secondary metabolites might be produced due to dehydration stress after harvest. Our findings supplied an important and useful theoretical basis for promoting the quality of Danshen and other medicinal plant materials.

  17. Identification of differentially expressed proteins in SH-SY5Y cells treated with resveratrol

    Institute of Scientific and Technical Information of China (English)

    Ying Wang; Zhong Dong; Hongyan Fan; Ming Chang; Guoyi Li; Linsen Hu

    2011-01-01

    To gain insight into the molecular mechanisms of resveratrol-mediated neuroprotection, two-dimensional difference gel electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to identify proteins differentially-expressed in SH-SY5Y cells treated with resveratrol. Compared with the control group, resveratrol treatment significantly affected the expression of four proteins: endoplasmic reticulum oxidoreductin 1-like protein alpha, p21-activated kinase 1, Archain 1, and T cell receptor beta chain. The former three were downregulated and the latter was upregulated. These proteins are primarily associated with endoplasmic reticulum stress, intracellular trafficking, and immune function.

  18. MEK/ERK signaling pathway in apoptosis of SW620 cell line and inhibition effect of resveratrol

    Institute of Scientific and Technical Information of China (English)

    Hao Chen; Zhi-Liang Jin; Hai Xu

    2016-01-01

    Objective: To study the involvement of MAPK MEK/ERK signaling transduction pathway in the apoptosis process of SW620 tumor cell line and the inhibition effect of resveratrol. Methods: SW620 cell lines were divided into 5 groups, namely, control group, PD98059 group, low-dose resveratrol group, mid-dose resveratrol group and high-dose resveratrol group. The inhibition rate of cell proliferation was detected by MTT method. The expression of apoptotic molecules and MEK/ERK signaling pathway related proteins were assayed by real-time PCR and Western blotting. Results: Compared with control group, the proliferation of cells treated with resveratrol was significantly inhibited. In the case of apoptotic molecules, the expression of Bax, Caspase 3 and Caspase 9 was increased significantly while the expression of anti-apoptotic molecule Bcl2 was decreased significantly in resveratrol groups with a dose-dependent manner. In the case of molecules in MEK/ERK signaling pathway, the expression of Ras, Raf, MEK and ERK1/2 was decreased significantly in resveratrol groups with a dose-dependent manner. Conclusions: PD98059 and resveratrol can effectively inhibit the proliferation of SW620 through inhibiting the MEK/ERK signaling pathway.

  19. A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and presystemic metabolism.

    Science.gov (United States)

    Seljak, Katarina Bolko; Berginc, Katja; Trontelj, Jurij; Zvonar, Alenka; Kristl, Albin; Gašperlin, Mirjana

    2014-11-01

    A mixed lipid-mixed surfactant self-microemulsifying drug delivery system (SMEDDS) was developed to exploit the health benefits of resveratrol, a Biopharmaceutical Classification System Class 2 natural polyphenol, subject to extensive intestinal presystemic metabolism. SMEDDS with a mixed lipid phase (castor oil/Capmul MCM 1:1) and a mixed surfactant phase (Kolliphor EL/Kolliphor RH 40 1:1) was developed and evaluated for its self-emulsifying properties and in vitro dispersion. The impact of SMEDDS on the permeability properties of resveratrol and its metabolite fluxes through the rat intestine and Caco-2 cells was monitored. The inhibitory effect of selected SMEDDS components on the efflux transporters multidrug resistance-associated protein and P-gp as well as cytotoxicity was assessed on Caco-2 cells. The formulation allowed for high resveratrol loading (122.5 mg/g SMEDDS), excellent self-emulsifying properties, and very rapid release. When formulated in SMEDDS, resveratrol metabolite efflux significantly declined. The formulation (SMEDDS without incorporated resveratrol) and its individual components did not compromise in vitro cell vitality and integrity. Mixed lipid-mixed surfactant SMEDDS is a prospective formulation to improve resveratrol biopharmaceutical, pharmacokinetic, and toxicological properties, leading the way to resveratrol use not only as a supplement but also as a pharmacological drug. PMID:25103361

  20. Analysis of the Resveratrol-binding Protein using Phage-displayed Random Peptide Library

    Institute of Scientific and Technical Information of China (English)

    Lei FENG; Jian JIN; Lian-Feng ZHANG; Ting YAN; Wen-Yi TAO

    2006-01-01

    Resveratrol, a plant polyphenol, is found in significant amounts in the skin of grapes and in some traditional herbs. It is reported to exert different biological activities, such as inhibiting lipid peroxidation,scavenging free radicals, inhibiting platelet aggregation, and anticancer activity. In order to screen the resveratrol-binding proteins, we synthesized biotinylated resveratrol, purified by liquid chromatography and immobilized it into streptavidin-coated microplate wells. 3-(4,5-Demethylthiazol-)-2,5-diphenyl tetrazolium bromide assay showed little change in the anticancer activity of biotinylated resveratrol in vitro. A random library of phage-displayed peptides was screened for binding to immobilized resveratrol to isolate resveratrolbinding proteins. Several peptides were found to bind to resveratrol specifically, which was proven by enzyme-linked immunosorbent assay. Through amino acid sequence analysis of the selected peptides and human proteins using the BLAST program, the results showed that resveratrol has an affinity for various proteins such as breast cancer-associated antigen, breast cancer resistance protein, death-associated transcription factor, and human cyclin-dependent kinase. These results demonstrate that our study provides a feasible method for the study of binding proteins of natural compounds using a phage-displayed random peptide library.

  1. Effect of resveratrol on cell cycle proteins in murine transplantable liver cancer

    Institute of Scientific and Technical Information of China (English)

    Liang Yu; Zhong-Jie Sun; Sheng-Li Wu; Cheng-En Pan

    2003-01-01

    AIM: To study the antitumour activity of resveratrol and its effect on the expression of ceil cycle proteins including cyclin D1, cyclin B1 and p34cdc2 in transplanted liver cancer of murine.METHODS: Murine transplanted hepatoma H22 model was used to evaluate the in vivo antitumor activity of resveratrol.Following abdominal administration of resveratrol, the change in tumour size was recorded and the protein expression of cyclin D1, cyclin B1 and p34cdc2 in the tumor and adjacent noncancerous liver tissues were measured by immunohistochemistry.RESULTS: Following treatment of H22 tumour bearing mice with resveratrol at 10 or 15 mg/kg bodyweight for 10 days,the growth of murine transplantable liver cancer was inhibited by 36.3% or 49.3%, respectively. The inhibitory effect was significant compared to that in control group (P<0.05).The level of expression of cyclin B1 and p34cdc2 protein was decreased in the transplantable murine hepatoma 22treated with resveratrol whereas the expression of cyclin D1 protein did not change.CONCLUSION: Resveratrol exhibits anti-tumour activities on murine hepatoma H22. The underlying anti-tumour mechanism of resveratrol might involve the inhibition of the cell cycle progression by decreasing the expression of cyclinB1 and p34cdc2 protein.

  2. Ammonia impairs glutamatergic communication in astroglial cells: protective role of resveratrol.

    Science.gov (United States)

    Bobermin, Larissa Daniele; Hansel, Gisele; Scherer, Emilene B S; Wyse, Angela T S; Souza, Diogo Onofre; Quincozes-Santos, André; Gonçalves, Carlos-Alberto

    2015-12-01

    Ammonia is a key toxin in the precipitation of hepatic encephalopathy (HE), a neuropsychiatric disorder associated with liver failure. In response to ammonia, various toxic events are triggered in astroglial cells, and alterations in brain glutamate communication are common. Resveratrol is a polyphenolic compound that has been extensively studied in pathological events because it presents several beneficial effects, including some in the central nervous system (CNS). We previously described that resveratrol is able to significantly modulate glial functioning and has a protective effect during ammonia challenge in vitro. In this study, we addressed the mechanisms by which resveratrol can protect C6 astroglial cells from glutamatergic alterations induced by ammonia. Resveratrol was able to prevent all the effects triggered by ammonia: (i) decrease in glutamate uptake activity and expression of the EAAC1 glutamate transporter, the main glutamate transporter present in C6 cells; (ii) increase of glutamate release, which was also dependent on the activation of the Na(+)-K(+)-Cl(-) co-transporter NKCC1; (iii) reduction in GS activity and intracellular GSH content; and (iv) impairment of Na(+)K(+)-ATPase activity. Interestingly, resveratrol, per se, also positively modulated the astroglial functions evaluated. Moreover, we demonstrated that heme oxygenase 1 (HO1), an enzyme that is part of the cellular defense system, mediated some of the effects of resveratrol. In conclusion, the mechanisms of the putative protective role of resveratrol against ammonia toxicity involve the modulation of pathways and molecules related to glutamate communication in astroglial cells.

  3. Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol-glucuronides

    Science.gov (United States)

    Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major...

  4. PRACTICAL PREPARATION OF RESVERATROL 3-O-β-D-GLUCURONIDE

    OpenAIRE

    Jungong, Christian S.; Novikov, Alexei V.

    2012-01-01

    A practical synthesis of resveratrol 3-O-β-D-glucuronide, suitable for preparation of large quantities, was developed using selective deacetylation of resveratrol triacetate with ammonium acetate. A simplified procedure for large scale preparation of resveratrol is also reported.

  5. Resveratrol and Alzheimer’s disease: message in a bottle on red wine and cognition

    Directory of Open Access Journals (Sweden)

    Alberto eGranzotto

    2014-05-01

    Full Text Available Cognitive impairment is the final outcome of a complex network of molecular mechanisms ultimately leading to dementia. Despite major efforts aimed at unraveling the molecular determinants of dementia of Alzheimer type (DAT, effective disease-modifying approaches are still missing. An interesting and still largely unexplored avenue is offered by nutraceutical intervention. For instance, robust epidemiological data have suggested that moderate intake of red wine may protect against several age-related pathological conditions (i.e.: cardiovascular diseases, diabetes, and cancer as well as DAT-related cognitive decline. Wine is highly enriched in many polyphenols, including resveratrol. Resveratrol is a well recognized antioxidant which may modulate metal ion deregulation outcomes as well as main features of the Alzheimer’s disease (AD brain. The review will discuss the potentiality of resveratrol as a neuroprotectant in dementia in relation to the oxidative stress produced by amyloid and metal dysmetabolism.

  6. Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia: a molecular docking study exploring possible neuroprotection

    Directory of Open Access Journals (Sweden)

    Anand Kumar Pandey

    2015-01-01

    Full Text Available The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was -37.848672 kJ/mol and -36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

  7. Resveratrol increases F508del-CFTR dependent salivary secretion in cystic fibrosis mice

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    Barbara Dhooghe

    2015-07-01

    Full Text Available Cystic fibrosis (CF is a fatal genetic disease associated with widespread exocrine gland dysfunction. Studies have suggested activating effects of resveratrol, a naturally-occurring polyphenol compound with antioxidant and anti-inflammatory properties, on CF transmembrane conductance regulator (CFTR protein function. We assayed, in F508del-CFTR homozygous (CF and in wild-type mice, the effect of resveratrol on salivary secretion in basal conditions, in response to inhibition by atropine (basal β-adrenergic-dependent component and to stimulation by isoprenaline (CFTR-dependent component. Both components of the salivary secretion were smaller in CF mice than in controls. Two hours after intraperitoneal administration of resveratrol (50 mg/kg dissolved in DMSO, the compound was detected in salivary glands. As in both CF and in wild-type mice, DMSO alone increased the response to isoprenaline in males but not in females, the effect of resveratrol was only measured in females. In wild-type mice, isoprenaline increased secretion by more than half. In CF mice, resveratrol rescued the response to isoprenaline, eliciting a 2.5-fold increase of β-adrenergic-stimulated secretion. We conclude that the salivary secretion assay is suitable to test DMSO-soluble CFTR modulators in female mice. We show that resveratrol applied in vivo to mice reaches salivary glands and increases β-adrenergic secretion. Immunolabelling of CFTR in human bronchial epithelial cells suggests that the effect is associated with increased CFTR protein expression. Our data support the view that resveratrol is beneficial for treating CF. The salivary secretion assay has a potential application to test efficacy of novel CF therapies.

  8. Effects of trans-resveratrol on paclitaxel-induced cell cycle arrest and its regulatory elements in human neuroblastoma SH-SY5Y cell line

    OpenAIRE

    Rigolio, R; Nicolini, G.; M. Miloso; Scuteri, A.; Erba, E.; Tredici, G

    2003-01-01

    INTRODUCTION: Resveratrol is a polyphenol found in grape and black wine. trans-resveratrol is the biologically active form of the polyphenolic compound. In different models it has been shown to have antioxidant, anti-inflammatory, antiplatelet aggregation activity. It has been also shown to have anticancer activity, to inhibit cell cycle progression and DNA synthesis Paclitaxel is an antineoplastic drug which is active against metastatic tumor of lung and breast but it causes peripheral ...

  9. Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway.

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    Xiaowen Feng

    Full Text Available Alzheimer's disease (AD is characterized by the accumulation of β-amyloid peptide (Aβ and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of β-amyloid peptide 25-35 (Aβ(25-35 and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aβ(25-35, and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and lactate dehydrogenase (LDH colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca(2+ homeostasis and attenuated Aβ(25-35 neurotoxicity. Additionally, Aβ(25-35-suppressed silent information regulator 1 (SIRT1 activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1. Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the β-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.

  10. Radiation stability of resveratrol in immobilization on poly vinyl pyrrolidone hydrogel dressing for dermatological use

    Science.gov (United States)

    Momesso, Roberta G. R. A. P.; Moreno, Carolina S.; Rogero, Sizue O.; Rogero, José R.; Spencer, Patrick J.; Lugão, Ademar B.

    2010-03-01

    The polyphenol trans-resveratrol is a natural phytoalexin, which is found in red wine and in a wide variety of plant species. Resveratrol displays a wide array of biological activities, such as modulation of lipid metabolism, anti-inflammatory and antioxidant activities. This active compound immobilized in polyvinylpyrrolidone (PVP) hydrogel could be very interesting for topical administration, as a dressing form for dermatological use. However, PVP hydrogel obtained by radiation-induced crosslinking can cause undesirable hydrolysis reactions in the active compound. The aim of this work was to verify the resveratrol stability after irradiation at 0.5 and 1 kGy in the presence of ethanol, methanol or tert-butyl alcohol. The integrity of these samples was compared to unirradiated resveratrol by HPLC. The PVP hydrogel matrix was characterized by gel fraction, swelling and in vitro biocompatibility test. The results of gel fraction and swelling degree were approximately 90% and 1600%, respectively. The cytotoxicity assay showed absence of toxicity for this formulation after crosslinking and sterilization, indicating that the PVP hydrogel formulation was appropriate for resveratrol immobilization to produce a dressing for dermatological use.

  11. Radiation stability of resveratrol in immobilization on poly vinyl pyrrolidone hydrogel dressing for dermatological use

    Energy Technology Data Exchange (ETDEWEB)

    Momesso, Roberta G.R.A.P., E-mail: robertapassarelli@yahoo.com.b [IPEN/CNEN-SP-Instituto de Pesquisas Energeticas e Nucleares, Avenida Professor Lineu Prestes, 2242, Cidade Universitaria, Sao Paulo, SP, CEP 05508-000 (Brazil); Moreno, Carolina S.; Rogero, Sizue O.; Rogero, Jose R.; Spencer, Patrick J.; Lugao, Ademar B. [IPEN/CNEN-SP-Instituto de Pesquisas Energeticas e Nucleares, Avenida Professor Lineu Prestes, 2242, Cidade Universitaria, Sao Paulo, SP, CEP 05508-000 (Brazil)

    2010-03-15

    The polyphenol trans-resveratrol is a natural phytoalexin, which is found in red wine and in a wide variety of plant species. Resveratrol displays a wide array of biological activities, such as modulation of lipid metabolism, anti-inflammatory and antioxidant activities. This active compound immobilized in polyvinylpyrrolidone (PVP) hydrogel could be very interesting for topical administration, as a dressing form for dermatological use. However, PVP hydrogel obtained by radiation-induced crosslinking can cause undesirable hydrolysis reactions in the active compound. The aim of this work was to verify the resveratrol stability after irradiation at 0.5 and 1 kGy in the presence of ethanol, methanol or tert-butyl alcohol. The integrity of these samples was compared to unirradiated resveratrol by HPLC. The PVP hydrogel matrix was characterized by gel fraction, swelling and in vitro biocompatibility test. The results of gel fraction and swelling degree were approximately 90% and 1600%, respectively. The cytotoxicity assay showed absence of toxicity for this formulation after crosslinking and sterilization, indicating that the PVP hydrogel formulation was appropriate for resveratrol immobilization to produce a dressing for dermatological use.

  12. Radiation stability of resveratrol in immobilization on poly vinyl pyrrolidone hydrogel dressing for dermatological use

    International Nuclear Information System (INIS)

    The polyphenol trans-resveratrol is a natural phytoalexin, which is found in red wine and in a wide variety of plant species. Resveratrol displays a wide array of biological activities, such as modulation of lipid metabolism, anti-inflammatory and antioxidant activities. This active compound immobilized in polyvinylpyrrolidone (PVP) hydrogel could be very interesting for topical administration, as a dressing form for dermatological use. However, PVP hydrogel obtained by radiation-induced crosslinking can cause undesirable hydrolysis reactions in the active compound. The aim of this work was to verify the resveratrol stability after irradiation at 0.5 and 1 kGy in the presence of ethanol, methanol or tert-butyl alcohol. The integrity of these samples was compared to unirradiated resveratrol by HPLC. The PVP hydrogel matrix was characterized by gel fraction, swelling and in vitro biocompatibility test. The results of gel fraction and swelling degree were approximately 90% and 1600%, respectively. The cytotoxicity assay showed absence of toxicity for this formulation after crosslinking and sterilization, indicating that the PVP hydrogel formulation was appropriate for resveratrol immobilization to produce a dressing for dermatological use.

  13. Major factors influencing antioxidant contents and antioxidant activity in grapes and wines

    Directory of Open Access Journals (Sweden)

    Jaromír Lachman

    2009-03-01

    Full Text Available Jaromír Lachman, Miloslav Šulc, Katerina Faitová, Vladimír PivecDepartment of Chemistry, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences, Prague, Czech RepublicAbstract: Phenolic compounds in wines, especially in red wines, possess strong antioxidant activity, have the largest effect in decreasing atherosclerosis by both hypolipemic and antioxidant mechanisms. The long-term uptake of red wine has a positive impact on antioxidant activity (AA of blood plasma in rats in vivo and increases AA by 15%–20% compared to a control group. In the article the effect of total phenolics (TP, total anthocyanins (TA, individual anthocyanins, procyanidins and phenolics contained in red grapes, musts, grape seeds and skins and wines on the AA is discussed. Significant impact of varieties, viticultural regions and locations, climate conditions and vintage has been shown. Likewise, the ways and individual stages of the vinification technology process, and storage conditions affect color, TP, TA, and AA and health aspects of produced wines. Resveratrol, another free radical scavenger mainly contained in the skins of grapes, inhibits the risk of cardiovascular diseases. Higher amounts of trans-resveratrol (RES have been found in wines from cool and wet climate regions and lesser amounts are typical for warm and dry regions. Changes in the TP content and AA affected by grape variety, vineyard location and winemaking process in white and blue varieties from different vineyards of the Czech Republic were studied. Significant differences in TP among varieties were found. Analysis of variance showed statistically high differences among red and white wines and growing locations. Wines differed significantly in TP content and AA increased significantly during the winemaking process. Statistically significant differences in AA values were found among growing areas, wines and varieties. Significant positive correlations between TP

  14. Improving solubility, stability, and cellular uptake of resveratrol by nanoencapsulation with chitosan and γ-poly (glutamic acid).

    Science.gov (United States)

    Jeon, Young Ok; Lee, Ji-Soo; Lee, Hyeon Gyu

    2016-11-01

    Resveratrol (RES), a polyphenolic compound found in grape skins, is a potent antioxidant with broad health benefits. However, its utilization in food has been limited by its poor water solubility, instability, and low bioavailability. The purpose of this study is to improve the solubility, stability, and cellular uptake of RES by nanoencapsulation using chitosan (CS) and γ-poly (glutamic acid) (γ-PGA). The size of nanoparticles significantly decreases with a decrease in the CS/γ-PGA ratio (p<0.05). The nanoparticle size with CS/γ-PGA ratio of 5 was 100-150nm. The entrapment efficiency and UV-light protection effect significantly increases (p<0.05), with an increase in the CS and γ-PGA concentration. The solubility of RES increases 3.2 and 4.2 times before and after lyophilization by nanoencapsulation, respectively. Compared with non-nanoencapsulated RES, the nanoencapsulated RES tends to maintain its solubility and antioxidant activity during storage. CS/γ-PGA nanoencapsulation was able to significantly enhance the transport of RES across a Caco-2 cell monolayer (p<0.05). The highest cellular uptake was found for nanoparticles prepared with 0.5mg/mL CS and 0.1mg/mL γ-PGA, which showed the highest solubility and antioxidant activity during storage. Therefore, CS/γ-PGA nanoencapsulation is found to be a potentially valuable technique for improving the solubility, stability, and cellular uptake of RES. PMID:27518454

  15. Effects of yerba maté, a plant extract formulation ("YGD") and resveratrol in 3T3-L1 adipogenesis.

    Science.gov (United States)

    Santos, Juliana C; Gotardo, Erica M F; Brianti, Mitsue T; Piraee, Mahmood; Gambero, Alessandra; Ribeiro, Marcelo L

    2014-01-01

    We aimed to evaluate the in vitro effects of yerba maté, YGD (a herbal preparation containing yerba maté, guarana and damiana), and resveratrol on adipogenesis. The anti-adipogenic effects of yerba mate, YGD, resveratrol and YGD + resveratrol and yerba mate + resveratrol combinations were evaluated in 3T3-L1 cells by Oil Red staining, cellular triglyceride content, and PCR quantitative array. The results demonstrated that all of the tested compounds inhibited adipogenesis. Yerba maté extract significantly down-regulated the expression of genes that play an important role in regulating adipogenesis, such as Adig, Axin, Cebpa, Fgf10, Lep, Lpl, and Pparγ2. In addition, these genes, YGD also repressed Bmp2, Ccnd1, Fasn, and Srebf1. Resveratrol also modulated the expression of Adig, Bmp2, Ccnd1, C/EBPα, Fasn, Fgf10, Lep, Lpl, and Pparγ2. Moreover, resveratrol repressed Cebpb, Cdk4, Fgf2, and Klf15. The yerba maté extract and YGD up-regulated the expression of genes involved in inhibiting adipogenesis, such as Dlk-1, Klf2, and Ucp1. Resveratrol also induced the expression of Klf2 and Ucp1. In addition resveratrol modulated the Ddit3, Foxo1, Sirt1, and Sirt2. The combined effects of these compounds on gene expression showed similar results observed from individual treatments. Our data indicates that the synergy between the compounds favors the inhibition of adipogenesis. PMID:25338179

  16. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition.

    Directory of Open Access Journals (Sweden)

    Ly Quoc Trung

    Full Text Available Natural killer (NK cell malignancies, particularly aggressive NK cell leukaemias and lymphomas, have poor prognoses. Although recent regimens with L-asparaginase substantially improved outcomes, novel therapeutic approaches are still needed to enhance clinical response. Resveratrol, a naturally occurring polyphenol, has been extensively studied for its anti-inflammatory, cardioprotective and anti-cancer activities. In this study, we investigated the potential anti-tumour activities of resveratrol against the NK cell lines KHYG-1, NKL, NK-92 and NK-YS. Resveratrol induced robust G0/G1 cell cycle arrest, significantly suppressed cell proliferation and induced apoptosis in a dose- and time-dependent manner for all four cell lines. In addition, resveratrol suppressed constitutively active STAT3 in all the cell lines and inhibited JAK2 phosphorylation but had no effect on other upstream mediators of STAT3 activation, such as PTEN, TYK2, and JAK1. Resveratrol also induced downregulation of the anti-apoptotic proteins MCL1 and survivin, two downstream effectors of the STAT3 pathway. Finally, resveratrol induced synergistic effect on the apoptotic and antiproliferative activities of L-asparaginase against KHYG-1, NKL and NK-92 cells. These results suggest that resveratrol may have therapeutic potential against NK cell malignancies. Furthermore, our finding that resveratrol is a bonafide JAK2 inhibitor extends its potential benefits to other diseases with dysregulated JAK2 signaling.

  17. Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia:a molecular docking study exploring possible neuroprotection

    Institute of Scientific and Technical Information of China (English)

    Anand Kumar Pandey; Pallab Bhattacharya; Swet Chand Shukla; Sudip Paul; Ranjana Patnaik

    2015-01-01

    The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs) has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the inter-action of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neu-rological function and brain edema were significantly alleviated, cerebral infarct volume was signiifcantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were signiifcantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 kJ/mol and –36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These ifndings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

  18. Resveratrol is neuroprotective and improves cognition in pentylenetetrazole-kindling model of epilepsy in rats

    Directory of Open Access Journals (Sweden)

    X J Meng

    2014-01-01

    Full Text Available S100B protein in serum and cerebral spinal fluid is increasingly used as a biochemical marker in early examinations after seizure to assess brain damage. Resveratrol, a nonflavonoid polyphenol, has been identified as a potent antiepileptic agent. However, a potential association between epilepsy with S100B protein in the cerebral spinal fluid and the sera of animal models lacks investigation. In this study, we evaluated the effects of resveratrol on behaviour and S100B protein levels in cerebral spinal fluid and serum in a rat model of chronic epilepsy induced via pentylenetetrazole kindling. By Morris water maze experiment analysis, we found that recovery of cognitive function in the resveratrol group (15 mg/kg/day, was significantly better than that of either the untreated or the vehicle groups. Further Nissl staining revealed that resveratrol significantly reduced pentylenetetrazole-induced death of neurons in the CA1 and CA3 regions of the hippocampus. Moreover, S100B protein levels in the cerebral spinal fluid and serum of rats treated with resveratrol were significantly reduced compared with the untreated and vehicle groups. These novel findings suggest an important mechanism of resveratrol and contribute to the treatment of epilepsy.

  19. Resveratrol--a potential inhibitor of biofilm formation in Vibrio cholerae.

    Science.gov (United States)

    Augustine, Nimmy; Goel, A K; Sivakumar, K C; Kumar, R Ajay; Thomas, Sabu

    2014-02-15

    Resveratrol, a phytochemical commonly found in the skin of grapes and berries, was tested for its biofilm inhibitory activity against Vibrio cholerae. Biofilm inhibition was assessed using crystal violet assay. MTT assay was performed to check the viability of the treated bacterial cells and the biofilm architecture was analysed using confocal laser scanning microscopy. The possible target of the compound was determined by docking analysis. Results showed that subinhibitory concentrations of the compound could significantly inhibit biofilm formation in V. cholerae in a concentration-dependent manner. AphB was found to be the putative target of resveratrol using docking analysis. The results generated in this study proved that resveratrol is a potent biofilm inhibitor of V. cholerae and can be used as a novel therapeutic agent against cholera. To our knowledge, this is the first report of resveratrol showing antibiofilm activity against V. cholerae. PMID:24182988

  20. Resveratrol Induces Apoptosis in Human Osteosarcoma MG63 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan Liu; Xin Wang; Yuxin Xie; Jingui Zhang; Qingshan Wang; Xianhui Xu

    2008-01-01

    OBJECTIVE To investigate apoptosis in human osteosarcoma MG63 cells induced by resveratrol and the molecular mechanism involved.METHODS MG63 cells were treated with different concentrations of resveratrol and transmission electron microscopy was used to observe morphological changes occurring in apoptosis.The MTT method was used to determine the inhibitory rate and flow cytometry was used to assess apoptosis and to analyze the expression of the p21ciP1/WAF1 and survivin proteins;the expression of p21ciP1/WAF1 and survivin mRNAs was analyzed by the reverse transcriptase polymerase chain reaction (RT-PCR).RESULTS After resveratrol treatment,the growth of the MG63 cells was significantly inhibited in a time- and dose-dependent fashion.By transmission electron microscopy,the cells displayed morphological changes characteristic of apoptosis,including formation of cytoplasmic vacuoles,chromatin condensation and margination.Flow cytometry showed that the growth of the cells was inhibited after resveratrol (10 mg/L and 20 mg/L) treatment.The inhibitory rates were (11.9 ±0.63)% and (19.7 ± 0.88)%respectively.The quantity of treated cells in G0/G1 transition was increased,but the number in the S phase and G2/M transition was decreased.A subdiploid peak was observed.The expression of p21ciP1/WAF1 was up-regulated while survivin was down-regulated.CONCLUSION Resveratrol can inhibit growth and induce apoptosis of MG63 cells.Its molecular mechanism might be related to modulation of survivin and p21ciP1/WAF1 expression.

  1. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

    International Nuclear Information System (INIS)

    Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

  2. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ying [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Nie, Ling [Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Yin, Yang-Guang [Emergency Department, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhou, Shi-Wen, E-mail: Zhoushiwen1956@yahoo.cn [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)

    2012-03-15

    Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

  3. Influence of Laccase and Tyrosinase on the Antioxidant Capacity of Selected Phenolic Compounds on Human Cell Lines

    Directory of Open Access Journals (Sweden)

    Matthias Riebel

    2015-09-01

    Full Text Available Polyphenolic compounds affect the color, odor and taste of numerous food products of plant origin. In addition to the visual and gustatory properties, they serve as radical scavengers and have antioxidant effects. Polyphenols, especially resveratrol in red wine, have gained increasing scientific and public interest due to their presumptive beneficial impact on human health. Enzymatic oxidation of phenolic compounds takes place under the influence of polyphenol oxidases (PPO, including tyrosinase and laccase. Several studies have demonstrated the radical scavenger effect of plants, food products and individual polyphenols in vitro, but, apart from resveratrol, such impact has not been proved in physiological test systems. Furthermore, only a few data exist on the antioxidant capacities of the enzymatic oxidation products of phenolic compounds generated by PPO. We report here first results about the antioxidant effects of phenolic substances, before and after oxidation by fungal model tyrosinase and laccase. In general, the common chemical 2,2-diphenyl-1-picrylhydrazyl assay and the biological tests using two different types of cell cultures (monocytes and endothelial cells delivered similar results. The phenols tested showed significant differences with respect to their antioxidant activity in all test systems. Their antioxidant capacities after enzymatic conversion decreased or increased depending on the individual PPO used.

  4. Oral Resveratrol Prevents Osteoarthritis Progression in C57BL/6J Mice Fed a High-Fat Diet

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    Hailun Gu

    2016-04-01

    Full Text Available The effects of resveratrol on osteoarthritis (OA pathogenesis have been demonstrated in vitro and in animal models employing intra-articular injections. However, the potential for oral resveratrol supplements to mediate protective effects on OA have not been examined. Therefore, the aim of the present study was to investigate the potential anti-OA effects of oral resveratrol on mice fed a high-fat diet (HFD. C57BL/6J male mice were fed either a standard diet or a HFD, and a subset of the latter also received varying doses of resveratrol. Twelve weeks later, all of the animals were sacrificed and knee joints were evaluated with histological, immunohistochemical, and TUNEL analyses. Mice that received a HFD had significantly greater body weights than the control mice and also exhibited features consistent with knee OA. The mice that received a HFD in combination with low, intermediate, or high doses of resveratrol were only slightly heavier than the control mice at the end of 12 weeks. Quantitative histological assessments indicated that resveratrol treatment partly recovered joint structure in the mice that received a HFD, while high doses of resveratrol prevented the degradation of type II collagen into C-telopeptide of type II collagen (CTX-II and retained type II collagen expression in cartilage. Furthermore, TUNEL analyses revealed a reduction in chondrocyte apoptosis in the resveratrol-treated mice compared with the HFD mice. Thus, oral resveratrol appears to exert anti-OA effects in a mouse model of HFD-induced OA, thereby highlighting the potential preventive and therapeutic value of administering resveratrol for obesity-associated OA.

  5. Resveratrol inhibits breast cancer stem-like cells and induces autophagy via suppressing Wnt/β-catenin signaling pathway.

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    Yujie Fu

    Full Text Available Resveratrol, a natural polyphenolic compound, is abundantly found in plant foods and has been extensively studied for its anti-cancer properties. Given the important role of CSCs (Cancer Stem Cells in breast tumorigenesis and progression, it is worth investigating the effects of resveratrol on CSCs. The article is an attempt to investigate the effects of resveratrol on breast CSCs. Resveratrol significantly inhibits the proliferation of BCSCs (breast cancer stem-like cells isolated from MCF-7 and SUM159, and decreased the percentage of BCSCs population, consequently reduced the size and number of mammospheres in non-adherent spherical clusters. Accordingly, the injection of resveratrol (100 mg/kg/d in NOD/SCID (nonobese diabetic/severe combined immunodeficient mice effectively inhibited the growth of xenograft tumors and reduced BCSC population in tumor cells. After the reimplantation of primary tumor cells into the secondary mice for 30 d, all 6 control inoculations produced tumors, while tumor cells derived from resveratrol-treated mice only caused 1 tumor of 6 inoculations. Further studies by TEM (Transmission electron microscopy analysis, GFP-LC3-II puncta formation assay and western blot for LC3-II, Beclin1 and Atg 7, showed that resveratrol induces autophagy in BCSCs. Moreover, resveratrol suppresses Wnt/β-catenin signaling pathway in BCSCs; over-expression of β-catenin by transfecting the plasmid markedly reduced resveratrol-induced cytotoxicity and autophagy in BCSCs. Our findings indicated that resveratrol inhibits BCSCs and induces autophagy via suppressing Wnt/β-catenin signaling pathway.

  6. Antimicrobial Activity of Resveratrol Analogues

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    Malik Chalal

    2014-06-01

    Full Text Available Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew. Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold. The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups and antimicrobial activity.

  7. Resveratrol Content in Strawberry Fruit is Affected by Preharvest Conditions

    Science.gov (United States)

    This study investigated the occurrence of resveratrol in Fragaria x ananassa Duchesne and the effect of pre-harvest conditions on resveratrol content. Both cis- and trans- resveratrol were detected in strawberry achenes (seeds) and pulp (receptacle tissue). Resveratrol was found to be higher in ache...

  8. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice

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    Bruckbauer Antje

    2012-08-01

    Full Text Available Abstract Background Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO mice. Methods 3T3-L1 mouse adipocytes were treated with Leucine (0.5 mM, β-hydroxy-β-methyl butyrate (HMB (5 μM or Resveratrol (200 nM alone or in combination. In addition, diet-induced obese mice were treated for 6-weeks with low (2 g/kg diet or high (10 g/kg diet dose HMB, Leucine (24 g/kg diet; 200% of normal level or low (12.5 mg/kg diet or high (225 mg/kg diet dose resveratrol, alone or as combination with leucine-resveratrol or HMB-resveratrol. Results Fatty acid oxidation, AMPK, Sirt1 and Sirt3 activity in 3T3-L1 adipocytes and in muscle cells, were significantly increased by the combinations compared to the individual treatments. Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT, insulin sensitivity (HOMAIR, improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect. Conclusion These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more

  9. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability

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    Neves AR

    2013-01-01

    Full Text Available Ana Rute Neves,1 Marlene Lúcio,1 Susana Martins,2,3 José Luís Costa Lima,1 Salette Reis11REQUIMTE, Chemistry Department, Faculty of Pharmacy, University of Porto, 2Laboratory for Pharmaceutical Technology/Research Centre in Pharmaceutical Sciences, Faculty of Pharmacy, University of Porto, 3Institute of Biomedical Engineering, University of Porto, PortugalIntroduction: Resveratrol is a polyphenol found in grapes and red wines. Interest in this polyphenol has increased due to its pharmacological cardio- and neuroprotective, chemopreventive, and antiaging effects, among others. Nevertheless, its pharmacokinetic properties are less favorable, since the compound has poor bioavailability, low water solubility, and is chemically unstable. To overcome these problems, we developed two novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance resveratrol's oral bioavailability for further use in medicines, supplements, and nutraceuticals.Methods and materials: Solid lipid nanoparticles (SLNs and nanostructured lipid carriers (NLCs loaded with resveratrol were successfully produced by a modified hot homogenization technique. These were completely characterized to evaluate the quality of the developed resveratrol-loaded nanoparticles.Results: Cryo-scanning electron microscopy morphology studies showed spherical and uniform nanoparticles with a smooth surface. An average resveratrol entrapment efficiency of ~70% was obtained for both SLNs and NLCs. Dynamic light scattering measurements gave a Z-average of 150–250 nm, polydispersity index of ~0.2, and a highly negative zeta potential of around −30 mV with no statistically significant differences in the presence of resveratrol. These characteristics remained unchanged for at least 2 months, suggesting good stability. Differential scanning calorimetry studies confirmed the solid state of the SLNs and NLCs at both room and body temperatures. The NLCs had a less ordered crystalline

  10. Resveratrol Protects against Methylglyoxal-Induced Hyperglycemia and Pancreatic Damage In Vivo

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    An-Sheng Cheng

    2015-04-01

    Full Text Available Methylglyoxal (MG has been found to cause inflammation and insulin resistance in vitro and in vivo in recent studies. Resveratrol has been proposed as an effective treatment that helps lower the risk of developing complications of diabetes. To study the significance of glycosylation-related stress on the pathology of diabetes, the effects of resveratrol were examined in a mouse model of diabetes induced by MG. Resveratrol was given via oral gavage in MG-treated mice, and diabetes-related tests and markers were assessed using biochemical and immunohistochemical analyses. Treatment with resveratrol markedly improved blood glucose level from the oral glucose tolerance test and promoted nuclear factor erythroid 2-related factor-2 (Nrf2 phosphorylation (p < 0.05 in the pancreas of MG-treated mice. However, these effects were abolished by retinoic acid, Nrf2 inhibitor, in resveratrol and retinoic acid-treated and MG-induced mice. These findings support that resveratrol may be useful in the treatment of type-2 diabetes by protecting against pancreatic cell dysfunction.

  11. Metformin and resveratrol ameliorate muscle insulin resistance through preventing lipolysis and inflammation in hypoxic adipose tissue.

    Science.gov (United States)

    Zhao, Wenjun; Li, Aiyun; Feng, Xin; Hou, Ting; Liu, Kang; Liu, Baolin; Zhang, Ning

    2016-09-01

    This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B. Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment. PMID:27343375

  12. Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats.

    Science.gov (United States)

    Alberdi, Goiuri; Rodríguez, Víctor M; Miranda, Jonatan; Macarulla, M Teresa; Churruca, Itziar; Portillo, María P

    2013-11-15

    The effect of resveratrol on thermogenesis in skeletal muscle and interscapular brown adipose tissue (IBAT) was investigated. Rats were fed an obesogenic diet supplemented with resveratrol (30mg/kg/day) or not supplemented for 6weeks. Resveratrol intake led to increased gene expression of mitochondrial-transcription-factor-A (TFAM), mitochondrial-protein-cytochrome-C-oxidase subunit-2 (COX2), sirtuin-1 (SIRT1), peroxisome-proliferator-activated-receptor-β/δ (PPARβ/δ) and proliferator-activated-receptor-gamma-coactivator1-α (PGC-1α) in IBAT and increased UCP1protein expression; however, peroxisome-proliferator-activated-receptor-α (PPARα) expression remained unchanged. In gastrocnemius muscle, resveratrol increased the gene expression of TFAM and COX2; however, no changes were observed in levels of SIRT1, PGC-1α and PPARβ/δ. Acetylated-PGC-1α was decreased in the resveratrol-treated group, indicating a higher level of activation, and a significant increase of UCP3 protein expression was observed in this group. The increases in UCP protein expression in two important thermogenic tissues after resveratrol treatment may contribute to increased whole-body energy dissipation, which may help to better understand the body-fat lowering effect of this polyphenol.

  13. Resveratrol production in bioreactor: Assessment of cell physiological states and plasmid segregational stability

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    Margarida S. Afonso

    2015-03-01

    Full Text Available Resveratrol is a plant secondary metabolite commonly found in peanuts and grapevines with significant health benefits. Recombinant organisms can produce large amounts of resveratrol and, in this work, Escherichia coli BW27784 was used to produce resveratrol in bioreactors while monitoring cell physiology and plasmid stability through flow cytometry and real-time qPCR, respectively. Initially, the influence of culture conditions and precursor addition was evaluated in screening assays and the data gathered was used to perform the bioreactor assays, allowing the production of 160 μg/mL of resveratrol. Cellular physiology and plasmid instability affected the final resveratrol production, with lower viability and plasmid copy numbers associated with lower yields. In sum, this study describes new tools to monitor the bioprocess, evaluating the effect of culture conditions, and its correlation with cell physiology and plasmid segregational stability, in order to define a viable and scalable bioprocess to fulfill the need for larger quantities of resveratrol.

  14. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Rezende Barbosa, Gabriella Lopes de; Almeida, Solange Maria de, E-mail: gabriellalopes@live.com [Universidade de Campinas (UNICAMP), Piracicaba, SP (Brazil). Escola de Odontologia. Departmento de Diagnostico Oral; Pimenta, Luiz Andre [University of North Carolina at Chapel Hill, School of Dentistry, Department of Dental Ecology, Chapel Hill, NC (United States)

    2016-05-01

    The purpose of this study was to perform a micro computerized tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a micro computerized tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey's post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05). The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues. (author)

  15. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

    Directory of Open Access Journals (Sweden)

    Gabriella Lopes DE REZENDE BARBOSA

    2016-01-01

    Full Text Available Abstract The purpose of this study was to perform a microcomputed tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a microcomputed tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey’s post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05. The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues.

  16. Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated hypertension in spontaneously hypertensive rats

    OpenAIRE

    Javkhedkar, AA; Quiroz, Y; Rodriguez-Iturbe, B; Vaziri, ND; Lokhandwala, MF; Banday, AA

    2015-01-01

    © 2015 the American Physiological Society. Compelling evidence supports the role of oxidative stress and renal interstitial inflammation in the pathogenesis of hypertension. Resveratrol is a polyphenolic stilbene, which can lower oxidative stress by activating the transcription factor nuclear factor-E2-related factor-2 (Nrf2), the master regulator of numerous genes encoding antioxidant and phase II-detoxifying enzymes and molecules. Given the role of oxidative stress and inflammation in the p...

  17. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity.

    Science.gov (United States)

    Qiao, Yi; Sun, Jin; Xia, Shufang; Tang, Xue; Shi, Yonghui; Le, Guowei

    2014-06-01

    Recent studies have investigated the anti-obesity effect of resveratrol, but the pathways through which resveratrol resists obesity are not clear. In the present study, we hypothesize that resveratrol exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes, and in turn, improving fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high-fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several biochemical markers are measured. Fluorescence in situ hybridization and flow cytometry are used to monitor and quantify the changes in gut microbiota. The key genes related to fat storage and metabolism in the liver and visceral adipose tissues are measured by real-time PCR. The results show that resveratrol (200 mg per kg per day) significantly lowers both body and visceral adipose weights, and reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut microbiota dysbiosis induced by the HF diet, including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Enterococcus faecalis, and increasing the growth of Lactobacillus and Bifidobacterium. Furthermore, resveratrol significantly increases the fasting-induced adipose factor (Fiaf, a key gene negatively regulated by intestinal microbes) expression in the intestine. Resveratrol significantly decreases mRNA expression of Lpl, Scd1, Ppar-γ, Acc1, and Fas related to fatty acids synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf expression. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and in turn, through the Fiaf signaling pathway, accelerates the development of obesity.

  18. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  19. Resveratrol-sulfates provide an intracellular reservoir for generation of parent resveratrol, which induces autophagy in cancer cells

    OpenAIRE

    Andreadi, Catherine; Britton, Robert G; Ketan R Patel; Brown, Karen

    2014-01-01

    Resveratrol has many proposed health benefits, including the prevention of cancers, but its low bioavailability is considered a limiting factor in translating these effects to humans. Based on in vivo and clinical studies we have shown that resveratrol is indeed rapidly metabolized by phase II enzymes, and that resveratrol sulfates are deconjugated by steroid sulfatases to afford free resveratrol in vitro and in vivo and hence act as an intracellular reservoir for resveratrol. Further, we hav...

  20. Quantification of skin penetration of antioxidants of varying lipophilicity.

    Science.gov (United States)

    Abla, M J; Banga, A K

    2013-02-01

    Antioxidants play a vital role in protecting the skin from environmental distress. As the skin is constantly exposed to harmful UV radiation, endogenous antioxidants present in the superficial layers of the skin neutralize reactive oxygen species. Over time, antioxidants become depleted and loss their protective effect on the skin. Therefore, supplementing skin with topical antioxidant can help replenish this loss and fight the oxidative stress. The objective of this study was to deliver antioxidants topically and quantify the amount permeated in the stratum corneum and underlying skin. Polyphenols (catechin, resveratrol and curcumin) and vitamin (retinol) with various lipophilic properties were delivered via porcine ear skin, using propylene glycol as a vehicle. The amount in the stratum corneum and underlying skin was quantified using tape stripping and skin extraction methods, respectively, and samples were analysed via HPLC. All four antioxidants permeated into the skin from the propylene glycol vehicle. The order of the amount of antioxidant in the stratum corneum was catechin > resveratrol~ retinol> curcumin, whereas that in the underlying skin was retinol > catechin~ resveratrol~ curcumin. Of the total amount of polyphenols in the skin, approximately 90% was retained in the stratum corneum whereas 10% was quantified in the underlying skin. In contrast, 10% of retinol was retained in the stratum corneum whereas 90% permeated in the underlying skin. Polyphenols (catechin, resveratrol and curcumin) showed high concentration in the stratum corneum whereas retinol showed high accumulation in the underlying layers of the skin.

  1. Protective Effects of Resveratrol on TNF-α-Induced Endothelial Cytotoxicity in Baboon Femoral Arterial Endothelial Cells

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    Juan Xiao

    2013-01-01

    Full Text Available Endothelial injury induced by inflammatory factors plays a critical role in the pathogenesis of cardiovascular disease. Endothelial cell (EC apoptosis, proliferation, migration, and cellular adhesion molecule (CAM expression contribute to the development of atherosclerosis. We investigated the effects of resveratrol (0.1–100 μM on the proliferation, migration, and CAM expression of primary cultures of baboon arterial endothelial cells (BAECs. In addition, we tested its effects under normal conditions as well as under inflammatory conditions induced by tumour necrosis factor-α (TNF-α administered either by cotreatment, pretreatment, or posttreatment. Immunocytochemistry, MTT, wound-healing, and flow cytometry assays were performed. The resveratrol treatment significantly enhanced BAEC proliferation and attenuated TNF-α-induced impairment of proliferation at the optimal doses of 1–50 µM. Resveratrol at a high dose (100 μM and TNF-α impaired BAEC migration, while low doses of resveratrol (1–50 μM attenuated TNF-α-induced impairment of BAEC migration. Moreover, resveratrol inhibited TNF-α-induced ICAM-1 and VCAM-1 expression. Taken together, our results suggest that the resveratrol protects BAECs after inflammatory stimulation as well as ameliorates inflammatory effects at low concentrations. Consequently, resveratrol should be considered as a candidate drug for the prevention and treatment of inflammatory vascular diseases.

  2. Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1β Axis in Microglia.

    Science.gov (United States)

    Sui, Da-ming; Xie, Qun; Yi, Wen-jing; Gupta, Sahil; Yu, Xi-ya; Li, Jin-bao; Wang, Jun; Wang, Jia-feng; Deng, Xiao-ming

    2016-01-01

    Sepsis-associated encephalopathy (SAE) is characterized as brain dysfunction associated with sepsis. In this study we sought to investigate the effects of resveratrol in mice with SAE, as well as its effects in NLRP3 inflammasome and IL-1β, which were critical in the pathogenesis of SAE. SAE was induced in mice via cecal ligation and puncture (CLP), and resveratrol was administered at two doses after surgery. Spatial learning memory functions were evaluated by Morris water maze testing. Apoptosis in the hippocampus was quantified using TUNEL assay. Inflammation in the hippocampus was quantified by measuring the levels of microglial activation, NLRP3, and IL-1β. CLP mice treated with resveratrol demonstrated a better spatial memory during water maze training. The TUNEL assay demonstrated significantly attenuated rates of apoptosis, in resveratrol treated mice, while decreasing the number of iba-1 positive microglia in the hippocampus region. NLRP3 expression and IL-1β cleavage were well inhibited by resveratrol dose-dependently. The in vitro results showed that in the BV2 cell lines resveratrol prevents ATP induced NLRP3 activation and IL-1β cleavage, which were reversed by the sirtuin 1 inhibitor, nicotinamide. In conclusion, resveratrol improves the spatial memory in mice with SAE and inhibits the NLRP3/IL-1β axis in the microglia.

  3. Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity, and to conjugate methylglyoxal.

    Science.gov (United States)

    Shen, Yixiao; Xu, Zhimin; Sheng, Zhanwu

    2017-02-01

    Glycation can generate advanced glycation end products (AGE) and its intermediates methylglyoxal (MGO) and glyoxal in foods, which increase the risk of developing diabetes diseases. In this study, the effect of resveratrol against AGE formation, carbohydrate-hydrolyzing enzyme activity and trapping MGO capability were evaluated. Resveratrol showed a significant inhibition capability against AGE formation in bovine serum albumin (BSA)-fructose, BSA-MGO and arginine-MGO models with inhibition percentages of 57.94, 85.95 and 99.35%, respectively. Furthermore, resveratrol acted as a competitive inhibitor for α-amylase with IC50 3.62μg/ml, while it behaved in an uncompetitive manner for α-glucosidase with an IC50 of 17.54μg/l. A prevention of BSA protein glycation was observed in the BSA-fructose model with addition of resveratrol. Three types of resveratrol-MGO adducts were identified in the model consisting of MGO and resveratrol. The results demonstrated that resveratrol has potential in reducing glycation in foods and retarding carbohydrate-hydrolyzing enzyme activities. PMID:27596404

  4. Wine Resveratrol: From the Ground Up.

    Science.gov (United States)

    Bavaresco, Luigi; Lucini, Luigi; Busconi, Matteo; Flamini, Riccardo; De Rosso, Mirko

    2016-01-01

    The ability of the grapevine to activate defense mechanisms against some pathogens has been shown to be linked to the synthesis of resveratrol and other stilbenes by the plant (inducible viniferins). Metabolized viniferins may also be produced or modified by extracellular enzymes released by the pathogen in an attempt to eliminate undesirable toxic compounds. Because of the important properties of resveratrol, there is increasing interest in producing wines with higher contents of this compound and a higher nutritional value. Many biotic and abiotic elicitors can trigger the resveratrol synthesis in the berries, and some examples are reported. Under the same elicitation pressure, viticultural and enological factors can substantially affect the resveratrol concentration in the wine. The production of high resveratrol-containing grapes and wines relies on quality-oriented viticulture (suitable terroirs and sustainable cultural practices) and winemaking technologies that avoid degradation of the compound. In general, the oenological practices commonly used to stabilize wine after fermentation do not affect resveratrol concentration, which shows considerable stability. Finally the paper reports on two sirtuin genes (SIRT) expressed in grapevine leaves and berries and the role of resveratrol on the deacetylation activity of the encoded enzymes. PMID:27089363

  5. Wine Resveratrol: From the Ground Up

    Science.gov (United States)

    Bavaresco, Luigi; Lucini, Luigi; Busconi, Matteo; Flamini, Riccardo; De Rosso, Mirko

    2016-01-01

    The ability of the grapevine to activate defense mechanisms against some pathogens has been shown to be linked to the synthesis of resveratrol and other stilbenes by the plant (inducible viniferins). Metabolized viniferins may also be produced or modified by extracellular enzymes released by the pathogen in an attempt to eliminate undesirable toxic compounds. Because of the important properties of resveratrol, there is increasing interest in producing wines with higher contents of this compound and a higher nutritional value. Many biotic and abiotic elicitors can trigger the resveratrol synthesis in the berries, and some examples are reported. Under the same elicitation pressure, viticultural and enological factors can substantially affect the resveratrol concentration in the wine. The production of high resveratrol-containing grapes and wines relies on quality-oriented viticulture (suitable terroirs and sustainable cultural practices) and winemaking technologies that avoid degradation of the compound. In general, the oenological practices commonly used to stabilize wine after fermentation do not affect resveratrol concentration, which shows considerable stability. Finally the paper reports on two sirtuin genes (SIRT) expressed in grapevine leaves and berries and the role of resveratrol on the deacetylation activity of the encoded enzymes. PMID:27089363

  6. Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats.

    Science.gov (United States)

    Abbas, Amr M

    2016-09-01

    Myocardial infarction (MI) is a common cause of mortality worldwide. Isorhapontigenin is a derivative of stilbene with chemical structure similar to resveratrol. The omega-3 fatty acids (FA) have beneficial effects on neurodegenerative, inflammatory, and cardiovascular diseases. The aim of this study was to investigate the effects of pretreatment with isorhapontigenin and omega-3 FA on rat model of isoproterenol-induced MI. Fifty-six rats were divided into seven groups: normal, normal + isorhapontigenin, normal + omega-3 FA, MI, MI + isorhapontigenin, MI + omega-3 FA, and MI + isorhapontigenin + omega-3 FA. Serum levels of cardiac marker enzymes [lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)], cardiac troponin I (cTnI), inflammatory markers [tumor necrosis factor-alpha (TNF-α) and interleukin-6], and lipid profile [triglycerides, total cholesterol (T.Ch), high and low density lipoproteins (HDL, LDL), and phospholipids] as well as cardiac levels of malondialdehyde and anti-oxidants [reduced glutathione (GSH), superoxide dismutase (SOD), and catalase)] were measured in all rats. ECG and histopathological examination were performed. Isoproterenol caused a significant elevation of ST segment, decreased R wave amplitude, HDL, and anti-oxidants, and increased LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, triglycerides, T.Ch, LDL, and phospholipids. Omega-3 FA or isorhapontigenin significantly decreased the ST segment elevation, LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, and phospholipids and increased R wave amplitude and anti-oxidants. The effects of combined omega-3 FA and isorhapontigenin were more significant than either of them alone. Therefore, we conclude that omega-3 FA and isorhapontigenin have a cardioprotective effect on rats with isoproterenol-induced MI through their anti-oxidant and anti-inflammatory actions. PMID:27193109

  7. Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats.

    Science.gov (United States)

    Abbas, Amr M

    2016-09-01

    Myocardial infarction (MI) is a common cause of mortality worldwide. Isorhapontigenin is a derivative of stilbene with chemical structure similar to resveratrol. The omega-3 fatty acids (FA) have beneficial effects on neurodegenerative, inflammatory, and cardiovascular diseases. The aim of this study was to investigate the effects of pretreatment with isorhapontigenin and omega-3 FA on rat model of isoproterenol-induced MI. Fifty-six rats were divided into seven groups: normal, normal + isorhapontigenin, normal + omega-3 FA, MI, MI + isorhapontigenin, MI + omega-3 FA, and MI + isorhapontigenin + omega-3 FA. Serum levels of cardiac marker enzymes [lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)], cardiac troponin I (cTnI), inflammatory markers [tumor necrosis factor-alpha (TNF-α) and interleukin-6], and lipid profile [triglycerides, total cholesterol (T.Ch), high and low density lipoproteins (HDL, LDL), and phospholipids] as well as cardiac levels of malondialdehyde and anti-oxidants [reduced glutathione (GSH), superoxide dismutase (SOD), and catalase)] were measured in all rats. ECG and histopathological examination were performed. Isoproterenol caused a significant elevation of ST segment, decreased R wave amplitude, HDL, and anti-oxidants, and increased LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, triglycerides, T.Ch, LDL, and phospholipids. Omega-3 FA or isorhapontigenin significantly decreased the ST segment elevation, LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, and phospholipids and increased R wave amplitude and anti-oxidants. The effects of combined omega-3 FA and isorhapontigenin were more significant than either of them alone. Therefore, we conclude that omega-3 FA and isorhapontigenin have a cardioprotective effect on rats with isoproterenol-induced MI through their anti-oxidant and anti-inflammatory actions.

  8. Resveratrol: Anti-Obesity Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Leixuri Aguirre

    2014-11-01

    Full Text Available Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPα and PPARγ in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by β-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule.

  9. Hepatoprotective effects of antioxidants in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Ricardo; Moreno-Otero; María; Trapero-Marugán

    2010-01-01

    We have read with interest the paper published in issue 2, volume 16 of World Journal of Gastroenterology 2010 by Nakamura et al, demonstrating that the antioxidant resveratrol (RVT) enhances hepatitis C virus (HCV) replication, consequently, they conclude that RVT is not a suitable antioxidant therapy for HCV chronic infection. The data raise some concern regarding the use of complementary and alternative medicine since the most frequent supplements taken by these patients are antioxidants or agents that m...

  10. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Juan-Juan Chen; Wen-Xia Wang; Jian-Ting Cai; Qin Du

    2005-01-01

    AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2and bax.METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500 mg/kg, 1000 mg/kg and 1500 mg/kg) was directly injected beside tumor body 6 times at an interval of 2 d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bcl-2and bax by immunohistochemical staining and PT-PCR.RESULTS: Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500 mg/kg,1 000 mg/kg and 1 500 mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics,including morphological changes of chromatin condensation,chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2 mL of normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg resveratrol was L3.68±0.37%, 13.8±0.43%,48.7±1.07%, 56.44±1.39% and 67±0.96%, respectively. The positive rate of bcl-2 protein of each group was 29.48±0.51%,27.56±1.40%, 11.86±0.97%, 5.7±0.84% and 3.92±0.85%,respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34±0.35%,20.88±0.91%, 40.02±1.20%, 45.72±0.88% and 52.3±1.54%,respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2 mL normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol,and 1 500 mg

  11. Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer.

    Science.gov (United States)

    Hadi, S M; Ullah, M F; Azmi, A S; Ahmad, A; Shamim, U; Zubair, H; Khan, H Y

    2010-06-01

    Plant polyphenols are important components of human diet, and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring anti-oxidants but also act as pro-oxidants catalyzing DNA degradation in the presence of metal ions such as copper. The plant polyphenol resveratrol confers resistance to plants against fungal agents and has been implicated as a cancer chemopreventive agent. Of particular interest is the observation that resveratrol has been found to induce apoptosis in cancer cell lines but not in normal cells. Over the last few years, we have shown that resveratrol is capable of causing DNA breakage in cells such as human lymphocytes. Such cellular DNA breakage is inhibited by copper specific chelators but not by iron and zinc chelating agents. Similar results are obtained by using permeabilized cells or with isolated nuclei, indicating that chromatin-bound copper is mobilized in this reaction. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and resveratrol to generate reactive oxygen species responsible for DNA cleavage. The results are in support of our hypothesis that anti-cancer mechanism of plant polyphenols involves mobilization of endogenous copper and the consequent pro-oxidant action. Such a mechanism better explains the anti-cancer effects of resveratrol, as it accounts for the preferential cytotoxicity towards cancer cells.

  12. Resveratrol Induces the Expression of Interleukin-10 and Brain-Derived Neurotrophic Factor in BV2 Microglia under Hypoxia

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    Juhyun Song

    2014-09-01

    Full Text Available Microglia are the resident macrophages of the central nervous system (CNS and play an important role in neuronal recovery by scavenging damaged neurons. However, overactivation of microglia leads to neuronal death that is associated with CNS disorders. Therefore, regulation of microglial activation has been suggested to be an important target for treatment of CNS diseases. In the present study, we investigated the beneficial effect of resveratrol, a natural phenol with antioxidant effects, in the microglial cell line, BV2, in a model of hypoxia injury. Resveratrol suppressed the mRNA expression of the pro-inflammatory molecule, tumor necrosis factor-α, and promoted the mRNA expression of the anti-inflammatory molecule, interleukin-10, in BV2 microglia under hypoxic conditions. In addition, resveratrol inhibited the activation of the transcription factor, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB, which is upstream in the control of inflammatory reactions in hypoxia-injured BV2 microglia. Moreover, resveratrol promoted the expression of brain-derived neurotrophic factor (BDNF in BV2 microglia under hypoxic stress. Overall, resveratrol may promote the beneficial function of microglia in ischemic brain injury.

  13. Resveratrol Ameliorates the Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Pektaş, Mehmet Bilgehan; Sadi, Gökhan; Koca, Halit Bugra; Yuksel, Yasemin; Vurmaz, Ayhan; Koca, Tulay; Tosun, Murat

    2016-02-01

    Preclinical Research Trans-resveratrol has a wide range of biological effects that reflect its antioxidant, anti-inflammatory, anticarcinogenic and cardioprotective properties. This study was conducted to elucidate the potential role of resveratrol on hepatic inflammation and the apoptotic pathway components Bcl-2, Bax and p53 in a streptozotocin (STZ)-induced rat model of diabetes mellitus. Inflammatory and apoptotic biomarkers indicated a reduction in hepatic erythropoietin (1.26-fold) and increased asymmetric dimethylarginine (3.9-fold), visfatin (1.6-fold), inflammatory interleukins and TNF-α contents (approximately twofold each) in the diabetic animals. Induction of inducible nitric oxide synthase gene (2.04-fold) and protein expression (1.24-fold) was also observed. Immunohistochemical studies showed enhancement of the apoptotic biomarkers Bax and p53 in diabetic animals. STZ-induced diabetic male Wistar rats were treated with resveratrol (20 mg/kg/day i.p.). Resveratrol succeeded to recover most of these inflammatory and apoptotic elements. Therefore, inflammatory and apoptotic pathways were proved to be affected by STZ-induced diabetes in several aspects and resveratrol might contribute hepatoprotective effects as evidenced from this study. PMID:26748675

  14. A novel enzyme-assisted ultrasonic approach for highly efficient extraction of resveratrol from Polygonum cuspidatum.

    Science.gov (United States)

    Lin, Jer-An; Kuo, Chia-Hung; Chen, Bao-Yuan; Li, Ying; Liu, Yung-Chuan; Chen, Jiann-Hwa; Shieh, Chwen-Jen

    2016-09-01

    Resveratrol is a promising multi-biofunctional phytochemical, which is abundant in Polygonum cuspidatum. Several methods for resveratrol extraction have been reported, while they often take a long extraction time accompanying with poor extraction yield. In this study, a novel enzyme-assisted ultrasonic approach for highly efficient extraction of resveratrol from P. cuspidatum was developed. According to results, the resveratrol yield significantly increased after glycosidases (Pectinex® or Viscozyme®) were applied in the process of extraction, and better extraction efficacy was found in the Pectinex®-assisted extraction compared to Viscozyme®-assisted extraction. Following, a 5-level-4-factor central composite rotatable design with response surface methodology (RSM) and artificial neural network (ANN) was selected to model and optimize the Pectinex®-assisted ultrasonic extraction. Based on the coefficient of determination (R(2)) calculated from the design data, ANN model displayed much more accurate in data fitting as compared to RSM model. The optimum conditions for the extraction determined by ANN model were substrate concentration of 5%, acoustic power of 150W, pH of 5.4, temperature of 55°C, the ratio of enzyme to substrate of 3950 polygalacturonase units (PGNU)/g of P. cuspidatum, and reaction time of 5h, which can lead to a significantly high resveratrol yield of 11.88mg/g.

  15. Induction of resveratrol biosynthesis in skins of three grape cultivars by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Resveratrol production and expression of the genes related to resveratrol biosynthesis were investigated in the skins of three Vitis vinifera cultivars Chardonnay, Koshu and an American hybrid grape, Muscat Bailey A (Bailey x Muscat Hamburg). Resveratrol concentration in the skins of all the grapes increased significantly when exposed to ultraviolet (UV-C, 254 nm) irradiation. The UV-induced resveratrol concentration in the grape skins was lower after veraison (onset of ripening) than before it. The maximum concentration of the UV-induced resveratrol in 'Muscat Bailey A' was higher than those in the other two cultivars. The relative mRNA expression levels of stilebene synthase (STS), phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) genes in grape skins 8 hr after UV irradiation were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results revealed that STS- and PAL-mRNA expressions were significantly increased by UV irradiation. STS-mRNA expressions in 'Muscat Bailey A' were higher than those in 'Chardonnay' throughout berry development. The UV-induced CHS-mRNA expression in the grape skins decreased before veraison and subsequently increased. (author)

  16. Longevity nutrients resveratrol, wines and grapes

    OpenAIRE

    Lekli, Istvan; Ray, Diptarka; Das, Dipak K

    2009-01-01

    A mild-to-moderate wine drinking has been linked with reduced cardiovascular, cerebrovascular, and peripheral vascular risk as well as reduced risk due to cancer. The reduced risk of cardiovascular disease associated with wine drinking is popularly known as French Paradox. A large number of reports exist in the literature indicating that resveratrol present in wine is primarily responsible for the cardioprotection associated with wine. Recently, resveratrol was shown to extend life span in ye...

  17. Resveratrol Inhibition of Cellular Respiration: New Paradigm for an Old Mechanism

    Directory of Open Access Journals (Sweden)

    Luis Alberto Madrigal-Perez

    2016-03-01

    Full Text Available Resveratrol (3,4′,5-trihydroxy-trans-stilbene, RSV has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1 decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2 increases adenosine monophosphate/adenosine diphosphate (AMP/ADP ratio that can lead to AMP protein kinase (AMPK activation, which is related to its health effects, and (3 increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol.

  18. Resveratrol: An Antiaging Drug with Potential Therapeutic Applications in Treating Diseases

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    Mercè Pallàs

    2009-12-01

    Full Text Available The prevention of aging is one of the most fascinating areas in biomedicine. The first step in the development of effective drugs for aging prevention is a knowledge of the biochemical pathways responsible for the cellular aging process. In this context it seems clear that free radicals play a key role in the aging process. However, in recent years it has been demonstrated that the families of enzymes called sirtuins, specifically situin 1 (SIRT1, have an anti-aging action. Thus, the natural compound resveratrol is a natural compound that shows a very strong activation of SIRT1 and also shows antioxidant effects. By activating sirtuin 1, resveratrol modulates the activity of numerous proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1 alpha, the FOXO family, Akt (protein kinase B and NFκβ. In the present review, we suggest that resveratrol may constitute a potential drug for prevention of ageing and for the treatment of several diseases due to its antioxidant properties and sirtuin activation.

  19. HPLC-F analysis of melatonin and resveratrol isomers in wine using an SPE procedure.

    Science.gov (United States)

    Mercolini, Laura; Addolorata Saracino, Maria; Bugamelli, Francesca; Ferranti, Anna; Malaguti, Marco; Hrelia, Silvana; Raggi, Maria Augusta

    2008-04-01

    An original analytical method has been developed for the determination of the antioxidants trans-resveratrol (t-RSV) and cis-resveratrol (c-RSV) and of melatonin (MLT) in red and white wine. The method is based on HPLC coupled to fluorescence detection. Separation was obtained by using a RP column (C8, 150 mm x 4.6 mm id, 5 mum) and a mobile phase composed of 79% aqueous phosphate buffer at pH 3.0 and 21% ACN. Fluorescence intensity was monitored at lambda = 386 nm while exciting at lambda = 298 nm, mirtazapine was used as the internal standard. A careful pretreatment of wine samples was developed, using SPE with C18 cartridges (100 mg, 1 mL). The calibration curves were linear over the following concentration ranges: 0.03-5.00 ng/mL for MLT, 3-500 ng/mL for t-RSV and 1-150 ng/mL for c-RSV. The LOD values were 0.01 ng/mL for MLT, 1 ng/mL for t-RSV and 0.3 ng/mL for c-RSV. Precision data, as well as extraction yield and sample purification results, were satisfactory. Thus, the method seems to be suitable for the analysis of MLT and resveratrol isomers in wine samples. Moreover, wine total polyphenol content and antioxidant activity were evaluated.

  20. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

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    Mozhgan Rezaie Kanavi

    2014-10-01

    Full Text Available The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV. To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.

  1. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    Science.gov (United States)

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice.

  2. Effects of Yerba maté, a Plant Extract Formulation (“YGD” and Resveratrol in 3T3-L1 Adipogenesis

    Directory of Open Access Journals (Sweden)

    Juliana C. Santos

    2014-10-01

    Full Text Available We aimed to evaluate the in vitro effects of yerba maté, YGD (a herbal preparation containing yerba maté, guarana and damiana, and resveratrol on adipogenesis. The anti-adipogenic effects of yerba mate, YGD, resveratrol and YGD + resveratrol and yerba mate + resveratrol combinations were evaluated in 3T3-L1 cells by Oil Red staining, cellular triglyceride content, and PCR quantitative array. The results demonstrated that all of the tested compounds inhibited adipogenesis. Yerba maté extract significantly down-regulated the expression of genes that play an important role in regulating adipogenesis, such as Adig, Axin, Cebpa, Fgf10, Lep, Lpl, and Pparγ2. In addition, these genes, YGD also repressed Bmp2, Ccnd1, Fasn, and Srebf1. Resveratrol also modulated the expression of Adig, Bmp2, Ccnd1, C/EBPα, Fasn, Fgf10, Lep, Lpl, and Pparγ2. Moreover, resveratrol repressed Cebpb, Cdk4, Fgf2, and Klf15. The yerba maté extract and YGD up-regulated the expression of genes involved in inhibiting adipogenesis, such as Dlk-1, Klf2, and Ucp1. Resveratrol also induced the expression of Klf2 and Ucp1. In addition resveratrol modulated the Ddit3, Foxo1, Sirt1, and Sirt2. The combined effects of these compounds on gene expression showed similar results observed from individual treatments. Our data indicates that the synergy between the compounds favors the inhibition of adipogenesis.

  3. The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans.

    Science.gov (United States)

    Wightman, Emma L; Haskell-Ramsay, Crystal F; Reay, Jonathon L; Williamson, Gary; Dew, Tristan; Zhang, Wei; Kennedy, David O

    2015-11-14

    Single doses of resveratrol have previously been shown to increase cerebral blood flow (CBF) with no clear effect on cognitive function or mood in healthy adults. Chronic resveratrol consumption may increase the poor bioavailability of resveratrol or otherwise potentiate its psychological effects. In this randomised, double-blind, placebo-controlled, parallel-groups study, a total of sixty adults aged between 18 and 30 years received either placebo or resveratrol for 28 d. On the 1st and 28th day of treatment, the performance of cognitively demanding tasks (serial subtractions, rapid visual information processing and 3-Back) (n 41 complete data sets) was assessed, alongside blood pressure (n 26) and acute (near-IR spectroscopy (NIRS)) and chronic (transcranial Doppler) measures of CBF (n 46). Subjective mood, sleep quality and health questionnaires were completed at weekly intervals (n 53/54). The results showed that the cognitive effects of resveratrol on day 1 were restricted to more accurate but slower serial subtraction task performance. The only cognitive finding on day 28 was a beneficial effect of resveratrol on the accuracy of the 3-Back task before treatment consumption. Subjective ratings of 'fatigue' were significantly lower across the entire 28 d in the resveratrol condition. Resveratrol also resulted in modulation of CBF parameters on day 1, as assessed by NIRS, and significantly increased diastolic blood pressure on day 28. Levels of resveratrol metabolites were significantly higher both before and after the day's treatment on day 28, in comparison with day 1. These results confirm the acute CBF effects of resveratrol and the lack of interpretable cognitive effects. PMID:26344014

  4. Anti-Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro-Inflammatory Mediators.

    Science.gov (United States)

    Singh, Ajeet Kumar; Vinayak, Manjula

    2016-07-01

    Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti-hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c-Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL-1β, TNF-α and IL-6 as well as inflammatory enzymes COX-2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX-2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti-nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27060370

  5. The Oxygenase CAO-1 of Neurospora crassa Is a Resveratrol Cleavage Enzyme

    KAUST Repository

    Diaz-Sanchez, V.

    2013-07-26

    The genome of the ascomycete Neurospora crassa encodes CAO-1 and CAO-2, two members of the carotenoid cleavage oxygenase family that target double bonds in different substrates. Previous studies demonstrated the role of CAO-2 in cleaving the C40 carotene torulene, a key step in the synthesis of the C35 apocarotenoid pigment neurosporaxanthin. In this work, we investigated the activity of CAO-1, assuming that it may provide retinal, the chromophore of the NOP-1 rhodopsin, by cleaving β-carotene. For this purpose, we tested CAO-1 activity with carotenoid substrates that were, however, not converted. In contrast and consistent with its sequence similarity to family members that act on stilbenes, CAO-1 cleaved the interphenyl Cα-Cβ double bond of resveratrol and its derivative piceatannol. CAO-1 did not convert five other similar stilbenes, indicating a requirement for a minimal number of unmodified hydroxyl groups in the stilbene background. Confirming its biological function in converting stilbenes, adding resveratrol led to a pronounced increase in cao-1 mRNA levels, while light, a key regulator of carotenoid metabolism, did not alter them. Targeted Δcao-1 mutants were not impaired by the presence of resveratrol, a phytoalexin active against different fungi, which did not significantly affect the growth and development of wild-type Neurospora. However, under partial sorbose toxicity, the Δcao-1 colonies exhibited faster radial growth than control strains in the presence of resveratrol, suggesting a moderate toxic effect of resveratrol cleavage products.

  6. Effects of Resveratrol Supplementation on Bone Growth in Young Rats and Microarchitecture and Remodeling in Ageing Rats

    Directory of Open Access Journals (Sweden)

    Alice M. C. Lee

    2014-12-01

    Full Text Available Osteoporosis is a highly prevalent skeletal disorder in the elderly that causes serious bone fractures. Peak bone mass achieved at adolescence has been shown to predict bone mass and osteoporosis related risk fracture later in life. Resveratrol, a natural polyphenol compound, may have the potential to promote bone formation and reduce bone resorption. However, it is unclear whether it can aid bone growth and bone mass accumulation during rapid growth and modulate bone metabolism during ageing. Using rat models, the current study investigated the potential effects of resveratrol supplementation during the rapid postnatal growth period and in late adulthood (early ageing on bone microarchitecture and metabolism. In the growth trial, 4-week-old male hooded Wistar rats on a normal chow diet were given resveratrol (2.5 mg/kg/day or vehicle control for 5 weeks. In the ageing trial, 6-month-old male hooded Wistar rats were treated with resveratrol (20 mg/kg/day or vehicle for 3 months. Treatment effects in the tibia were examined by μ-computer tomography (μ-CT analysis, bone histomorphometric measurements and reverse transcription-polymerase chain reaction (RT-PCR gene expression analysis. Resveratrol treatment did not affect trabecular bone volume and bone remodeling indices in the youth animal model. Resveratrol supplementation in the early ageing rats tended to decrease trabecular bone volume, Sirt1 gene expression and increased expression of adipogenesis-related genes in bone, all of which were statistically insignificant. However, it decreased osteocalcin expression (p = 0.03. Furthermore, serum levels of bone resorption marker C-terminal telopeptides type I collagen (CTX-1 were significantly elevated in the resveratrol supplementation group (p = 0.02 with no changes observed in serum levels of bone formation marker alkaline phosphatase (ALP. These results in rat models suggest that resveratrol supplementation does not significantly affect bone

  7. Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors

    OpenAIRE

    Qing Liu; CheongTaek Kim; Yang Hee Jo; Seon Beom Kim; Bang Yeon Hwang; Mi Kyeong Lee

    2015-01-01

    Resveratrol (1), a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore, resveratrol derivatives were prepared to improve bioavailability and anti-melanogenesis activity. Nine resveratrol derivatives including five alkyl ether derivatives with C2H5, C4H9, C5H11, C6H13, and C8H...

  8. Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Karine Zortea

    2016-01-01

    Full Text Available Background: Patients with schizophrenia (SZ are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease (CVD. The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ. Methods and Results: This is a four-week randomized, double-blind controlled trial (registration No.: NCT 02062190 in which 19 men with a diagnosis of SZ, aged 18 to 65, were assigned to either a resveratrol supplement group (200 mg/day or a placebo group (200 mg/day. In short, we did not observe significant changes after resveratrol supplementation. In the placebo group, we found a significant increase in total cholesterol levels (p = 0.024 and in LDL-cholesterol (p = 0.002, as well as a decrease in body fat percentage (p = 0.038. The placebo group also showed an increase in triglycerides (9.19% and a reduction in HDL-cholesterol (4.88%. In the resveratrol group, triglycerides decreased (7.64%. Conclusion: In summary, oral resveratrol in reasonably low dosages (200 mg daily brought no differences to body weight, waist circumference, glucose, and total cholesterol. It was possible to note that the lipid profile in the placebo group worsened and, although no significant differences were found, we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels.

  9. Danske rødvine indeholder kun lidt resveratrol

    DEFF Research Database (Denmark)

    Andersen, Heidi D.; Cohen, Malene; Tønning, Joan;

    2008-01-01

    Resveratrol er et af de biologisk aktive stoffer i rødvin. Tidligere bestemmelser viser, at vin lavet på druen Pinot Noir har det højeste indhold af resveratrol. I Danmark dyrkes andre sorter til vinfremstilling. Her beskrives for første gang indholdet af resveratrol i vine lavet på druer dyrket i...

  10. Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats.

    Directory of Open Access Journals (Sweden)

    Francesca Delucchi

    Full Text Available Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM. We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i the progenitor cell pool, and (ii the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128 with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54 or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64. Twenty-five rats constituted the control group (C. After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic "milieu" on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1 a significant reduction in ±dP/dt in comparison with C group, 2 a prolongation of isovolumic contraction/relaxation times, 3 an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing

  11. Development of a lozenge for oral transmucosal delivery of trans-resveratrol in humans: proof of concept.

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    Otis L Blanchard

    Full Text Available Resveratrol provides multiple physiologic benefits which promote healthspan in various model species and clinical trials support continued exploration of resveratrol treatment in humans. However, there remains concern regarding low bioavailability and wide inter-individual differences in absorption and metabolism in humans, which suggests a great need to develop novel methods for resveratrol delivery. We hypothesized that oral transmucosal delivery, using a lozenge composed of a resveratrol-excipient matrix, would allow resveratrol to be absorbed rapidly into the bloodstream. We pursued proof of concept through two experiments. In the first experiment, the solubility of trans-resveratrol (tRES in water and 2.0 M solutions of dextrose, fructose, ribose, sucrose, and xylitol was determined using HPLC. Independent t-tests with a Bonferroni correction were used to compare the solubility of tRES in each of the solutions to that in water. tRES was significantly more soluble in the ribose solution (p = 0.0013 than in the other four solutions. Given the enhanced solubility of tRES in a ribose solution, a resveratrol-ribose matrix was developed into a lozenge suitable for human consumption. Lozenges were prepared, each containing 146±5.5 mg tRES per 2000 mg of lozenge mass. Two healthy human participants consumed one of the prepared lozenges following an overnight fast. Venipuncture was performed immediately before and 15, 30, 45, and 60 minutes following lozenge administration. Maximal plasma concentrations (Cmax for tRES alone (i.e., resveratrol metabolites not included were 325 and 332 ng⋅mL(-1 for the two participants at 15 minute post-administration for both individuals. These results suggest a resveratrol-ribose matrix lozenge can achieve greater Cmax and enter the bloodstream faster than previously reported dosage forms for gastrointestinal absorption. While this study is limited by small sample size and only one method of resveratrol

  12. Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

    Science.gov (United States)

    Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

    2012-01-01

    It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water

  13. Determination of the phytoalexin resveratrol (3,5,4'-trihydroxystilbene) in peanuts and pistachios by high-performance liquid chromatographic diode array (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS).

    Science.gov (United States)

    Tokuşoglu, Ozlem; Unal, Mustafa Kemal; Yemiş, Fadim

    2005-06-15

    The phytoalexin resveratrol (3,5,4'-trihydroxystilbene) in edible peanut (Arachis hypogaea L.) and pistachio (Pistacia vera L.) varieties grown in Turkey was analyzed by high-performance liquid chromatographic diode array and gas chromatography-mass spectrometric detection. trans-Resveratrol in six peanut varieties, five pistachio varieties, and four market samples ranged between 0.03 and 1.92 microg/g. The Cerezlik 5025 peanut (1.92 +/- 0.01 microg/g) and Ohadi pistachio genotype (1.67 +/- 0.01 microg/g) had significantly higher trans-resveratrol contents. Peanuts contained 0.03-1.92 microg/g (av = 0.84 microg/g) of trans-resveratrol, whereas pistachio contained 0.09-1.67 microg/g (av = 1.15 microg/g). With exposure to UV light for 1 min, trans-resveratrol concentrations of samples ranged from 0.02 to 1.47 microg/g and those of cis-resveratrol from 0.008 to 0.32 microg/g. The occurrence of resveratrol in peanut and pistachio was confirmed by total ion chromatograms (TIC) of bis[trimethylsilyl]trifluoroacetamide derivatives of resveratrol isomers and comparison of the mass spectral fragmentation data with those of a resveratrol standard. Formation of the cis-isomer in pistachios was higher than in peanuts. PMID:15941348

  14. Resveratrol and health from a consumer perspective

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-01-01

    Resveratrol is an ingredient widely researched, with growing evidence of health-promoting effects. However, the reactions of supplement or food consumers to resveratrol has not been researched, and the ingredient is yet unknown to most consumers. We used respective literature and our own resverat......Resveratrol is an ingredient widely researched, with growing evidence of health-promoting effects. However, the reactions of supplement or food consumers to resveratrol has not been researched, and the ingredient is yet unknown to most consumers. We used respective literature and our own...... interest in resveratrol and lack relevant knowledge, especially in Denmark. Favorable attitudes were explained by health outcome expectations, use of complementary and alternative medicine, and interest in the indulgence dimension of food. Nonscientifically phrased communication led tomore favorable...... attitudes inDanish consumers; scientifically phrased communication, though,made U.S. consumers more likely to retain favorable attitudes in the presence of contradictory evidence.We discuss future research directions in different cultural backgrounds and market contexts and for different foods....

  15. Resveratrol Trimers from Seed Cake of Paeonia rockii

    Directory of Open Access Journals (Sweden)

    Pu Liu

    2014-11-01

    Full Text Available In the course of screening natural products for antibacterial activities, a total acetone extract of the seed cake of Paeonia rockii showed significant effects against bacterial strains. Bioactivity-guided fractionation of the EtOAc-soluble fraction of the total acetone extract resulted in the isolation and identification of five resveratrol trimers, including rockiiol C (1, gnetin H (2, suffruticosol A (3, suffruticosol B (4 and suffruticosol C (5. The relative configuration of these compounds was elucidated mainly by comprehensive 1D and 2D-NMR experiments. Compound 1 was a new compound. All isolated compounds exhibited strong antibacterial activities against Gram-positive bacteria.

  16. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

    DEFF Research Database (Denmark)

    Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue;

    2016-01-01

    . The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

  17. Effect of resveratrol on L-type calcium current in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    Li-ping ZHANG; Jing-xiang YIN; Zheng LIU; Yi ZHANG; Qing-shan WANG; Juan ZHAO

    2006-01-01

    Aim: To study the effect of resveratrol on L-type calcium current (ICa-L) in isolated rat ventricular myocytes and the mechanisms underlying these effects. Methods:ICa-L was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. Results: Resveratrol (10-40 μmol/L) reduced the peak amplitude of ICa-L and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 μmol/L)decreased the peak amplitude of ICa-L from -14.2± 1.5 pA/pF to -10.5± 1.5 pA/pF (P<0.05), -7.5±2.4 pA/pF (P<0.01), and -5.2±1.2 pA/pF (P<0.01), respectively.Resveratrol (40 μmol/L) shifted the steady-state activation curve of ICa-L to the right and changed the half-activation potential (V0.5) from -19.4±0.4 mV to -15.4±1.9 mV (P<0.05). Resveratrol at a concentration of 40 μmol/L did not affect the steady-state inactivation curve of ICa-L, but did markedly shift the timedependent recovery curve of ICa-L to the right, and slow down the recovery of ICa-L from inactivation. Sodium orthovanadate (Na3VO4; 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01). Conclusion: Resveratrol inhibited ICa- L mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.

  18. Resveratrol nanosuspensions: interaction of preservatives with nanocrystal production.

    Science.gov (United States)

    Kobierski, S; Ofori-Kwakye, K; Müller, R H; Keck, C M

    2011-12-01

    The effect of six different preservatives on the production process and stability of resveratrol nanosuspensions was investigated. Nanosuspensions of the anti-oxidant resveratrol were prepared by high pressure homogenization (1,500 bar, 20 homogenization cycles). The preservatives used were: caprylyl glycol (0.75%), Euxyl PE 9010 (1.0%), Hydrolite-5 (2.0), Phenonip (0.75%), Rokonsal PB-5 (0.5%) and MultiEx Naturotics (2.0%). Preservation is essential for oral and dermal nanosuspensions, but can impair the stability. The effect of the preservatives on stability as a function of cycle numbers was determined by size measurements (photon correlation spectroscopy (PCS), laser diffraction (LD) and light microscopy). Zeta potential measurements were performed for determination of the Stern potential (measurements in water) and as stability criterion (measurements in original dispersion medium), to elucidate the mechanism of destabilization. The preservatives could be placed into three groups. Hydrolite-5 did not affect the production process and the short term stability, sizes were practically identical to the preservative-free nanosuspension (e.g. PCS diameters 196 nm and 184 nm, respectively). All other preservatives impaired the stability medium to pronounced, being most pronounced for MultiEx Naturotics. Hydrolite-5 is recommended as preservative of choice. A mechanistic model was developed to explain the absence and the different degrees of destabilization. In general, when screening for suitable preservatives, suspensions are produced, different preservatives added and the size changes are monitored over long-term. The destabilizing effect of the preservatives on nanosuspensions became evident when added in the production process immediately, thus this can be used as a screening tool for optimal, non-destabilizing preservatives, replacing or minimizing time-consuming long-term stability studies.

  19. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

    Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  20. Effects of exercise training and resveratrol on vascular health in aging

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva

    2016-01-01

    Cardiovascular disease is a leading cause of death in the western world with aging being one of the strongest predictors of cardiovascular events. Aging is associated with impaired vascular function due to endothelial dysfunction and altered redox balance, partly caused by an increased formation ...... effects of physical activity. Regular physical activity remains the most effective way of maintaining and improving vascular health status and caution should be taken regarding potential interference of supplements on training adaptations....... of the observed detrimental effects of aging on vascular function. The effects of aging and physical activity on vascular function are, in part, related to alterations in cellular signaling through sirtuin-1, AMPK and the estrogen receptor. The polyphenol resveratrol can activate these same pathways and has......, in animals and in vitro models, been shown to act as a partial mimetic of physical activity. However, support for beneficial effects of resveratrol in human is weak and studies even show that resveratrol supplementation, similarly to supplementation with other antioxidants, can counteract the positive...

  1. Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

    Directory of Open Access Journals (Sweden)

    Lee Trollope

    2014-12-01

    Full Text Available The phytoalexin trans-resveratrol, 5-[(1E-2-(4-hydroxyphenylethenyl]-1,3-benzenediol, is a well-known, potent antioxidant having a variety of possible biomedical applications. However, its adverse physicochemical properties (low stability, poor aqueous solubility limit such applications and its inclusion in cyclodextrins (CDs has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD, permethylated β-CD and 2,6-dimethylated β-CD are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential scanning calorimetry. To complement the solid-state data, phase-solubility studies were conducted using a series of CDs (native and variously derivatised to establish their effect on the aqueous solubility of trans-resveratrol and to estimate association constants for complex formation.

  2. The effect of resveratrol in combination with irradiation and chemotherapy. Study using Merkel cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Brunner, M.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, R. [Medical University of Vienna, Maxillo-Facial Surgery, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and -biology, Vienna (Austria); Houben, R. [University Hospital Wuerzburg, Department of Dermatology, Wuerzburg (Germany); Bigenzahn, J. [CeMM-Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna (Austria)

    2014-01-15

    Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested. (orig.) [German] Das Merkelzellkarzinom (MCC) ist ein seltener, jedoch hochmaligner Tumor der Haut. Sowohl Strahlentherapie oder Chemotherapie sind moegliche therapeutische Optionen. In dieser Studie wurde untersucht, ob das Flavonoid Resveratrol die Wirkung der Strahlen- oder Chemotherapie in MCC-Zelllinien verbessert. Die beiden MCC-Zelllinien MCC13 und MCC26 wurden mit ansteigenden Dosen von Resveratrol behandelt. Kombinationsexperimente wurden mit Cisplatin und Etoposid durchgefuehrt und die Koloniebildung in ''Colony-Forming''-Assays nach erfolgter sequentieller Bestrahlung mit 1, 2, 3, 4, 6 und 8 Gy gemessen. Desweiteren wurde die Apoptose mittels Durchflusszytometrie bestimmt. Die

  3. The synergic effect of regular exercise and resveratrol on kainate-induced oxidative stress and seizure activity in mice.

    Science.gov (United States)

    Kim, Hee-jae; Kim, Il-Kon; Song, Wook; Lee, Jin; Park, Sok

    2013-01-01

    The synergic effect of regular exercise and resveratrol, a polyphenolic compound with potent antioxidant activity, was investigated against kainate-induced seizures and oxidative stress in mice. After 6 weeks of swimming training, the total body weight decreased and the blood concentration of lactate stabilized statistically in comparison with the sedentary mice, indicate that the training program increased the aerobic resistance of mice. Kainate (30 mg/kg) evoked seizure activity 5 min after injection, and seizure activity was measured seizure rating scores every 5 min up to 2 h. As previously well known experiments, regular exercise and resveratrol (40 mg/kg, daily supplementation for 6 weeks) have an inhibitory effect on kainate-induced seizure activity and oxidative stress. In particularly, a synergistic cooperation of regular exercise and resveratrol was observed in seizure activity, mortality and oxidative stress especially in SOD activity. These results suggest that regular exercise along with an anti-convulsant agent such as resveratrol could be a more efficient method for the prevention of seizure development than exercise alone. PMID:23054073

  4. Neuroprotective mechanisms of resveratrol in cerebral ischemia%白藜芦醇在脑缺血中的神经保护机制

    Institute of Scientific and Technical Information of China (English)

    牛丽辉

    2014-01-01

    白藜芦醇是一种存在于许多种植物的多酚植物抗菌素.许多研究表明,白藜芦醇具有神经保护作用.文章从抗细胞凋亡、抗炎症反应和抗氧化等方面对白藜芦醇在脑缺血时的神经保护机制进行了综述.%Resveratrol is a polyphenol phytoalexin presents in a variety of plant species.Many studies have shown that resveratrol exerts neuroprotective effects.This article reviewes the neuroprotective mechanisms of resveratrol in cerebral ischemia from the aspects of antiapoptosis,antioxidant and antiinflammatory.

  5. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1

    Science.gov (United States)

    Wang, Songbo; Liang, Xingwei; Yang, Qiyuan; Fu, Xing; Rogers, Carl J.; Zhu, Meijun; Rodgers, B. D.; Jiang, Qingyan; Dodson, Michael V.; Du, Min

    2014-01-01

    Objective Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus, we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). Methods CD1 female mice (5-month-old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. Results Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers including uncoupling protein 1 (UCP1), PR domain-containing 16 (PRDM16), Cell death-inducing DFFA-like effector A (Cidea), elongation of very long chain fatty acids protein 3 (Elovl3), peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), cytochrome C and pyruvate dehydrogenase (PDH) in differentiated iWAT stromal vascular cells (SVC), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. Conclusion Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial anti-obesity effects may be partly due to the browning of WAT and as a consequence, increased oxygen consumption. PMID:25761413

  6. Resveratrol improves health and survival of mice on a high-calorie diet

    Science.gov (United States)

    Baur, Joseph A.; Pearson, Kevin J.; Price, Nathan L.; Jamieson, Hamish A.; Lerin, Carles; Kalra, Avash; Prabhu, Vinayakumar V.; Allard, Joanne S.; Lopez-Lluch, Guillermo; Lewis, Kaitlyn; Pistell, Paul J.; Poosala, Suresh; Becker, Kevin G.; Boss, Olivier; Gwinn, Dana; Wang, Mingyi; Ramaswamy, Sharan; Fishbein, Kenneth W.; Spencer, Richard G.; Lakatta, Edward G.; Le Couteur, David; Shaw, Reuben J.; Navas, Placido; Puigserver, Pere; Ingram, Donald K.; de Cabo, Rafael; Sinclair, David A.

    2016-01-01

    Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing. PMID:17086191

  7. Resveratrol can prevent CCl₄-induced liver injury by inhibiting Notch signaling pathway.

    Science.gov (United States)

    Tanriverdi, Gamze; Kaya-Dagistanli, Fatma; Ayla, Sule; Demirci, Sibel; Eser, Mediha; Unal, Z Seda; Cengiz, Mujgan; Oktar, Huseyin

    2016-07-01

    We investigated whether Notch signaling was increased in an experimental liver fibrosis model and examined the effects of resveratrol on Notch expression. Rats were divided into four groups: the control group, injected with physiological saline; the CCl₄ group; the CCl₄ plus resveratrol group; and the resveratrol group. After treatment, immunostaining was performed to detect Notch1, Notch3, Notch4, transforming growth factor (TGF)-beta, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA), and TUNEL assays were performed to evaluate apoptosis. Sirius red staining was used to detect fibrosis. Samples were also biochemically evaluated for glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation, and protein oxidation. GSH, GPx, and catalase activities were significantly decreased (p⟨0.001) in the CCl₄ group. Distinct collagen accumulation was detected around the central vein and portal areas, and numbers of Notch1-, Notch3-, and Notch4-positive cells were significantly increased (p⟨0.001) in fibrotic areas in the CCl₄ group. Increased expression of Notch proteins in fibrotic areas may support the role of Notch in mediating signaling associated with liver fibrosis through activation of hepatic stellate and progenitor cells. In contrast, resveratrol prevented liver fibrosis by decreasing lipid peroxidation and may be effective for inhibiting Notch signaling. PMID:26742567

  8. Growth-stimulatory effect of resveratrol in human cancer cells.

    Science.gov (United States)

    Fukui, Masayuki; Yamabe, Noriko; Kang, Ki Sung; Zhu, Bao Ting

    2010-08-01

    Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations (cells, but this effect was not observed in several other human cell lines tested. Analysis of cell signaling molecules showed that resveratrol induced the activation of JNK, p38, Akt, and NF-kappaB signaling pathways in these cells. Further analysis using pharmacological inhibitors showed that only the NF-kappaB inhibitor (BAY11-7082) abrogated the growth-stimulatory effect of resveratrol in cultured cells. In athymic nude mice, resveratrol at 16.5 mg/kg body weight enhanced the growth of MDA-MB-435s xenografts compared to the control group, while resveratrol at the 33 mg/kg body weight dose did not have a similar effect. Additional analyses confirmed that resveratrol stimulated cancer cell growth in vivo through activation of the NF-kappaB signaling pathway. Taken together, these observations suggest that resveratrol at low concentrations could stimulate the growth of certain types of human cancer cells in vivo. This cell type-specific mitogenic effect of resveratrol may also partly contribute to the procarcinogenic effect of alcohol consumption (rich in resveratrol) in the development of certain human cancers.

  9. Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells.

    Science.gov (United States)

    Zhong, L-X; Zhang, Y; Wu, M-L; Liu, Y-N; Zhang, P; Chen, X-Y; Kong, Q-Y; Liu, J; Li, H

    2016-01-01

    Autophagic activity reflects cellular response to drug treatment and can be regulated by STAT3 signaling. Resveratrol inhibits STAT3 activation and causes remarkable growth arrest and cell death of ovarian cancer (OC) cells. However, the autophagic status and its relevance with resveratrol's anti-OC effects remain unclear. We analyzed the states of autophagic activities, the nature of autophagosomes and the levels of autophagy-related proteins (LC-3, Beclin 1 and STAT3) in resveratrol-treated CAOV-3 and OVCAR-3 OC cells using multiple approaches. We elucidated the correlation of STAT3 inhibition with autophagic activity by treating OC cells with an upstream inhibitor of STAT proteins, AG490. Resveratrol efficiently suppressed growth, induced apoptosis and inactivated STAT3 signaling of the two OC cell lines. We found enhanced autophagic activity accompanied with Beclin-1 upregulation and LC3 enzymatic cleavage in resveratrol-treated OC cells. Immunofluorescent (IF) microscopic and IF-based confocal examinations demonstrated the accumulation of cytoplasmic granules co-labeled with LC3 and cytochrome C in resveratrol- or AG490-treated OC cells. Using electron microscopy, we confirmed an increase in autophagosomes and mitochondrial spheroids in either resveratrol- or AG490-treated OC cells. This study demonstrates the abilities of resveratrol to enhance apoptotic and autophagic activities in OC cells, presumably via inactivating STAT3 signaling. Resveratrol or the selective JAK2 inhibitor also leads to mitochondrial turnover, which would be unfavorable for OC cell survival and sensitize OC cells to resveratrol. PMID:27551495

  10. Antioxidant-rich leaf extract of Barringtonia racemosa significantly alters the in vitro expression of genes encoding enzymes that are involved in methylglyoxal degradation III

    Science.gov (United States)

    Kong, Kin Weng; Abdul Aziz, Azlina; Razali, Nurhanani; Aminuddin, Norhaniza

    2016-01-01

    Background Barringtonia racemosa is a medicinal plant belonging to the Lecythidaceae family. The water extract of B. racemosa leaf (BLE) has been shown to be rich in polyphenols. Despite the diverse medicinal properties of B. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking. Methods In this study, the effect of the antioxidant-rich BLE on gene expression in HepG2 cells was investigated using microarray analysis in order to shed more light on the molecular mechanism associated with the medicinal properties of the plant. Results Microarray analysis showed that a total of 138 genes were significantly altered in response to BLE treatment (p compound. Conclusions BLE has the potential to be developed into a novel chemopreventive agent provided that the cytotoxic effects related to methylglyoxal accumulation are minimized in normal cells that rely on aerobic glycolysis for energy supply. PMID:27635343

  11. A new resveratrol tetramer from Caragana rosea

    Institute of Scientific and Technical Information of China (English)

    Guo Xun Yang; Chang Qi Hu

    2007-01-01

    In a continual effort to search for any anti-HIV agent from traditional Chinese medicine, one new resveratrol tetramer,cararosinols B, was isolated from the ethanol extract of aerial parts of Caragana rosea. Its structure was elucidated by spectroscopic analysis and comparison with known compounds.

  12. Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Stefan Bereswill

    Full Text Available BACKGROUND: The health beneficial effects of Resveratrol, Curcumin and Simvastatin have been demonstrated in various experimental models of inflammation. We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that after peroral administration of Resveratrol, Curcumin or Simvastatin, mice were protected from ileitis development and survived the acute phase of inflammation whereas all Placebo treated controls died. In particular, Resveratrol treatment resulted in longer-term survival. Resveratrol, Curcumin or Simvastatin treated animals displayed significantly increased numbers of regulatory T cells and augmented intestinal epithelial cell proliferation/regeneration in the ileum mucosa compared to placebo control animals. In contrast, mucosal T lymphocyte and neutrophilic granulocyte numbers in treated mice were reduced. In addition, levels of the anti-inflammatory cytokine IL-10 in ileum, mesenteric lymph nodes and spleen were increased whereas pro-inflammatory cytokine expression (IL-23p19, IFN-γ, TNF-α, IL-6, MCP-1 was found to be significantly lower in the ileum of treated animals as compared to Placebo controls. Furthermore, treated animals displayed not only fewer pro-inflammatory enterobacteria and enterococci but also higher anti-inflammatory lactobacilli and bifidobacteria loads. Most importantly, treatment with all three compounds preserved intestinal barrier functions as indicated by reduced bacterial translocation rates into spleen, liver, kidney and blood. CONCLUSION/SIGNIFICANCE: Oral treatment with Resveratrol, Curcumin or Simvastatin ameliorates acute small intestinal inflammation by down-regulating Th1-type immune responses and prevents bacterial translocation by maintaining gut barrier function. These findings provide novel

  13. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    Science.gov (United States)

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway.

  14. Anti-tumor Properties of cis-Resveratrol Methylated Analogues in Metastatic Mouse Melanoma Cells

    Science.gov (United States)

    Morris, Valery L.; Toseef, Tayyaba; Nazumudeen, Fathima B.; Rivoira, Christian; Spatafora, Carmela; Tringali, Corrado; Rotenberg, Susan A.

    2015-01-01

    Resveratrol (E-3,5,4’-trihydroxystilbene) is a polyphenol found in red wine that has been shown to have multiple anti-cancer properties. Although cis (Z) and trans (E) isomers of resveratrol occur in nature, the cis form is not biologically active. However, methylation at key positions of the cis form results in more potent anti-cancer properties. This study determined that synthetic cis-polymethoxystilbenes (methylated analogues of cis-resveratrol) inhibited cancer-related phenotypes of metastatic B16 F10 and non-metastatic B16 F1 mouse melanoma cells. In contrast with cis or trans-resveratrol and trans-polymethoxystilbene which were ineffective at 10 μM, cis-polymethoxystilbenes inhibited motility and proliferation of melanoma cells with low micromolar specificity (IC50 <10 μM). Inhibitory effects by cis-polymethoxystilbenes were significantly stronger with B16 F10 cells and were accompanied by decreased expression of β-tubulin and pleckstrin homology domain-interacting protein, a marker of metastatic B16 cells. Thus, cis-polymethoxystilbenes have potential as chemotherapeutic agents for metastatic melanoma. PMID:25567208

  15. Effect of Resveratrol as Caloric Restriction Mimetic and Environmental Enrichment on Neurobehavioural Responses in Young Healthy Mice

    Directory of Open Access Journals (Sweden)

    Mustapha Shehu Muhammad

    2014-01-01

    Full Text Available Caloric restriction and environmental enrichment have been separately reported to possess health benefits such as improvement in motor and cognitive functions. Resveratrol, a natural polyphenolic compound, has been reported to be caloric restriction mimetic. This study therefore aims to investigate the potential benefit of the combination of resveratrol as CR and EE on learning and memory, motor coordination, and motor endurance in young healthy mice. Fifty mice of both sexes were randomly divided into five groups of 10 animals each: group I animals received carboxymethylcellulose (CMC orally per kg/day (control, group II animals were maintained on every other day feeding, group III animals received resveratrol 50 mg/kg, suspended in 10 g/L of (CMC orally per kg/day, group IV animals received CMC and were kept in an enriched environment, and group V animals received resveratrol 50 mg/kg and were kept in EE. The treatment lasted for four weeks. On days 26, 27, and 28 of the study period, the animals were subjected to neurobehavioural evaluation. The results obtained showed that there was no significant change (P>0.05 in neurobehavioural responses in all the groups when compared to the control which indicates that 50 mg/kg of resveratrol administration and EE have no significant effects on neurobehavioural responses in young healthy mice over a period of four weeks.

  16. Nanoscale Delivery of Resveratrol towards Enhancement of Supplements and Nutraceuticals

    OpenAIRE

    Ana Rute Neves; Susana Martins; Marcela A. Segundo; Salette Reis

    2016-01-01

    Resveratrol was investigated in terms of its stability, biocompatibility and intestinal permeability across Caco-2 cell monolayers in its free form or encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs and NLCs presented a mean diameter between 160 and 190 nm, high negative zeta potential of −30 mV and resveratrol entrapment efficiency of 80%, suggesting they are suitable for resveratrol oral delivery. Nanoencapsulation effectively protected resver...

  17. Pleiotropic mechanisms facilitated by resveratrol and its metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Calamini, Barbara; Ratia, Kiira; Malkowski, Michael G.; Cuendet, Muriel; Pezzuto, John M.; Santarsiero, Bernard D.; Mesecar, Andrew D. (Geneva); (Hawaii); (SUNYB); (UIC)

    2010-07-01

    Resveratrol has demonstrated cancer chemopreventive activity in animal models and some clinical trials are underway. In addition, resveratrol was shown to promote cell survival, increase lifespan and mimic caloric restriction, thereby improving health and survival of mice on high-calorie diet. All of these effects are potentially mediated by the pleiotropic interactions of resveratrol with different enzyme targets including COX-1 (cyclo-oxygenase-1) and COX-2, NAD{sup +}-dependent histone deacetylase SIRT1 (sirtuin 1) and QR2 (quinone reductase 2). Nonetheless, the health benefits elicited by resveratrol as a direct result of these interactions with molecular targets have been questioned, since it is rapidly and extensively metabolized to sulfate and glucuronide conjugates, resulting in low plasma concentrations. To help resolve these issues, we tested the ability of resveratrol and its metabolites to modulate the function of some known targets in vitro. In the present study, we have shown that COX-1, COX-2 and QR2 are potently inhibited by resveratrol, and that COX-1 and COX-2 are also inhibited by the resveratrol 4{prime}-O-sulfate metabolite. We determined the X-ray structure of resveratrol bound to COX-1 and demonstrate that it occupies the COX active site similar to other NSAIDs (non-steroidal anti-inflammatory drugs). Finally, we have observed that resveratrol 3- and 4?-O-sulfate metabolites activate SIRT1 equipotently to resveratrol, but that activation is probably a substrate-dependent phenomenon with little in vivo relevance. Overall, the results of this study suggest that in vivo an interplay between resveratrol and its metabolites with different molecular targets may be responsible for the overall beneficial health effects previously attributed only to resveratrol itself.

  18. Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

    OpenAIRE

    Zoe eFonseca-Kelly; Mayssa eNassrallah; Jorge eUribe; Khan, Reas S.; Kimberly eDine; Mahasweta eDutt; Shindler, Kenneth S.

    2012-01-01

    Resveratrol is a naturally-occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current st...

  19. Juice, pulp and seeds fractionated from dry climate primocane raspberry cultivars (Rubus idaeus) have significantly different antioxidant capacity, anthocyanin content and color.

    Science.gov (United States)

    Snyder, Shannon M; Low, Richard M; Stocks, Janet C; Eggett, Dennis L; Parker, Tory L

    2012-12-01

    Raspberries contain flavonoid antioxidants whose relative concentrations may vary between the juice, pulp, and seed fractions. Oxygen radical absorbance capacity (ORAC), total anthocyanin content, and berry color were determined for six cultivars of primocane raspberries grown in a dry climate (Utah, USA). Significant ORAC differences were found between juice (18.4 ± 0.39 μmol TE/g), pulp (24.45 ± 0.43), and seeds (273.27 ± 11.15) with all Utah cultivars combined. A significantly higher concentration of anthocyanins was present in Utah raspberry juice (20.86 ± 0.35 mg cyanidin-3-glucoside eq./100 g), compared to pulp (13.96 ± 0.35). Anthocyanin content of juice and pulp were significantly positively correlated with dark color (L*). This is the first report of fractional differences in dry climate raspberries, and has implications for the juice and supplement industries.

  20. Assessment of resveratrol, apocynin and taurine on mechanical-metabolic uncoupling and oxidative stress in a mouse model of duchenne muscular dystrophy: A comparison with the gold standard, α-methyl prednisolone.

    Science.gov (United States)

    Capogrosso, Roberta Francesca; Cozzoli, Anna; Mantuano, Paola; Camerino, Giulia Maria; Massari, Ada Maria; Sblendorio, Valeriana Teresa; De Bellis, Michela; Tamma, Roberto; Giustino, Arcangela; Nico, Beatrice; Montagnani, Monica; De Luca, Annamaria

    2016-04-01

    Antioxidants have a great potential as adjuvant therapeutics in patients with Duchenne muscular dystrophy, although systematic comparisons at pre-clinical level are limited. The present study is a head-to-head assessment, in the exercised mdx mouse model of DMD, of natural compounds, resveratrol and apocynin, and of the amino acid taurine, in comparison with the gold standard α-methyl prednisolone (PDN). The rationale was to target the overproduction of reactive oxygen species (ROS) via disease-related pathways that are worsened by mechanical-metabolic impairment such as inflammation and over-activity of NADPH oxidase (NOX) (taurine and apocynin, respectively) or the failing ROS detoxification mechanisms via sirtuin-1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (resveratrol). Resveratrol (100mg/kg i.p. 5days/week), apocynin (38mg/kg/day per os), taurine (1g/kg/day per os), and PDN (1mg/kg i.p., 5days/week) were administered for 4-5 weeks to mdx mice in parallel with a standard protocol of treadmill exercise and the outcome was evaluated with a multidisciplinary approach in vivo and ex vivo on pathology-related end-points and biomarkers of oxidative stress. Resveratrol≥taurine>apocynin enhanced in vivo mouse force similarly to PDN. All the compounds reduced the production of superoxide anion, assessed by dihydroethidium staining, with apocynin being as effective as PDN, and ameliorated electrophysiological biomarkers of oxidative stress. Resveratrol also significantly reduced plasma levels of creatine kinase and lactate dehydrogenase. Force of isolated muscles was little ameliorated. However, the three compounds improved histopathology of gastrocnemius muscle more than PDN. Taurine>apocynin>PDN significantly decreased activated NF-kB positive myofibers. Thus, compounds targeting NOX-ROS or SIRT1/PGC-1α pathways differently modulate clinically relevant DMD-related endpoints according to their mechanism of action. With the

  1. Assessment of resveratrol, apocynin and taurine on mechanical-metabolic uncoupling and oxidative stress in a mouse model of duchenne muscular dystrophy: A comparison with the gold standard, α-methyl prednisolone.

    Science.gov (United States)

    Capogrosso, Roberta Francesca; Cozzoli, Anna; Mantuano, Paola; Camerino, Giulia Maria; Massari, Ada Maria; Sblendorio, Valeriana Teresa; De Bellis, Michela; Tamma, Roberto; Giustino, Arcangela; Nico, Beatrice; Montagnani, Monica; De Luca, Annamaria

    2016-04-01

    Antioxidants have a great potential as adjuvant therapeutics in patients with Duchenne muscular dystrophy, although systematic comparisons at pre-clinical level are limited. The present study is a head-to-head assessment, in the exercised mdx mouse model of DMD, of natural compounds, resveratrol and apocynin, and of the amino acid taurine, in comparison with the gold standard α-methyl prednisolone (PDN). The rationale was to target the overproduction of reactive oxygen species (ROS) via disease-related pathways that are worsened by mechanical-metabolic impairment such as inflammation and over-activity of NADPH oxidase (NOX) (taurine and apocynin, respectively) or the failing ROS detoxification mechanisms via sirtuin-1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (resveratrol). Resveratrol (100mg/kg i.p. 5days/week), apocynin (38mg/kg/day per os), taurine (1g/kg/day per os), and PDN (1mg/kg i.p., 5days/week) were administered for 4-5 weeks to mdx mice in parallel with a standard protocol of treadmill exercise and the outcome was evaluated with a multidisciplinary approach in vivo and ex vivo on pathology-related end-points and biomarkers of oxidative stress. Resveratrol≥taurine>apocynin enhanced in vivo mouse force similarly to PDN. All the compounds reduced the production of superoxide anion, assessed by dihydroethidium staining, with apocynin being as effective as PDN, and ameliorated electrophysiological biomarkers of oxidative stress. Resveratrol also significantly reduced plasma levels of creatine kinase and lactate dehydrogenase. Force of isolated muscles was little ameliorated. However, the three compounds improved histopathology of gastrocnemius muscle more than PDN. Taurine>apocynin>PDN significantly decreased activated NF-kB positive myofibers. Thus, compounds targeting NOX-ROS or SIRT1/PGC-1α pathways differently modulate clinically relevant DMD-related endpoints according to their mechanism of action. With the

  2. Effect of resveratrol on microcirculation disorder and lung injury following severe acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Yong Meng; Mei Zhang; Jun Xu; Xue-Min Liu; Qing-Yong Ma

    2005-01-01

    AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP).METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum.Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally.Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination.Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR.RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology:high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs 0.03±0.03mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2±87.8 g/L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10),dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05).CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).

  3. Effect of resveratrol and in combination with 5-FU on murine liver cancer

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li Wu; Zhong-Jie Sun; Liang Yu; Ke-Wei Meng; Xing-Lei Qin; Cheng-En Pan

    2004-01-01

    AIM: To study the anti-tumor effect of resveratrol and in combination with 5-FU on murine liver cancer.METHODS: Transplantable murine hepatoma22 model was used to evaluate the anti-tumor activity of resveratrol (RES)alone or in combination with 5-FU in vivo. H22 cell cycles were analyzed with flow cytometry.RESULTS: Resveratrol could inhibit the growth of murine hepatoma22, after the mice bearing H22 tumor were treated with 10 mg/kg or 15 mg/kg resveratrol for ten days, and the inhibition rates were 36.3% (n = 10) and 49.3% (n = 9),respectively, which increased obviously compared with that in control group (85±22 vs 68±17, P<0.01). RES could induce the S phase arrest of H22 cells, and increase the persentage of cells in S phase from 59.1% (n = 9) to 73.5% (n = 9) in a dose-dependent manner (P<0.05). The enhanced inhibition of tumor growth by 5-FU was also observed in hepatoma22 bearing mice when 5-FU was administered in combination with 10 mg/kg resveratrol. The inhibition rates for 20 mg/kg or 10 mg/kg 5-FU in combination with 10 mg/kg resveratrol were 77.4% and 72.4%, respectively, compared with the group of 20 mg/kg or 10 mg/kg 5-FU alone, in which the inhibition rates were 53.4% and 43.8%, respectively (n = 8). There was a statistical significance between the combination group and 5-FU group.CONCLUSION: RES could induce the S phase arrest of H22cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. These results suggest that resveratrol, as a biochemical modulator to enhance the therapeutic effects of 5-FU, may be potentially useful in cancer chemotherapy.

  4. Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis.

    Science.gov (United States)

    Kumar, Vivek; Pandey, Ankita; Jahan, Sadaf; Shukla, Rajendra Kumar; Kumar, Dipak; Srivastava, Akriti; Singh, Shripriya; Rajpurohit, Chetan Singh; Yadav, Sanjay; Khanna, Vinay Kumar; Pant, Aditya Bhushan

    2016-01-01

    The plethora of literature has supported the potential benefits of Resveratrol (RV) as a life-extending as well as an anticancer compound. However, these two functional discrepancies resulted at different concentration ranges. Likewise, the role of Resveratrol on adult neurogenesis still remains controversial and less understood despite its well documented health benefits. To gather insight into the biological effects of RV on neurogenesis, we evaluated the possible effects of the compound on the proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of aged rats. Resveratrol exerted biphasic effects on NPCs; low concentrations (10 μM) stimulated cell proliferation mediated by increased phosphorylation of extracellular signal-regulated kinases (ERKs) and p38 kinases, whereas high concentrations (>20 μM) exhibited inhibitory effects. Administration of Resveratrol (20 mg/kg body weight) to adult rats significantly increased the number of newly generated cells in the hippocampus, with upregulation of p-CREB and SIRT1 proteins implicated in neuronal survival and lifespan extension respectively. We have successfully demonstrated that Resveratrol exhibits dose dependent discrepancies and at a lower concentration can have a positive impact on the proliferation, survival of NPCs and aged rat hippocampal neurogenesis implicating its potential as a candidate for restorative therapies against age related disorders. PMID:27334554

  5. Synthesis and skin gene analysis of 4'-acetoxy-resveratrol (4AR), therapeutic potential for dermal applications.

    Science.gov (United States)

    Lephart, Edwin D; Acerson, Mark J; Andrus, Merritt B

    2016-07-15

    Resveratrol (RV) 1, a plant polyphenol, has proven effective in commercial products yet drawbacks include low bioavailability due to rapid metabolism. Structural modifications have led to a 4'-acetoxy analog 2 (4AR) now produced using a selective one-step esterification reaction. The one-step synthesis is shown together with expression of skin genes using human dermal models to establish 4AR 2 benefits to skin health. 4AR 2 at 1% in qPCR experiments using a human skin model significantly increased gene expression of the anti-aging factor, SIRT 1 by over 3.3-fold, extracellular matrix proteins collagen III, IV, elastin and tissue inhibitors of metalloproteinases (TIMP 1, 2), anti-oxidants CAT, LOX, superoxide dismutase (SOD 1, 2), metallothioneins (MT1H, MT1H), skin aging biomarkers fibrillin (FBN1), laminin (LAMB1), proliferating cell nuclear antigen (PCNA), skin growth factors (HBEGF, IGF1, NGF and TGF). 4AR 2 also decreased gene expression of inflammatory and skin-aging molecules (IL-1, IL-6, IL-8, COX-2, TNGRSF) and S100 calcium binding proteins A8, A9. These findings suggest that 4AR 2 has potential for topically treatment and prevention of skin aging. PMID:27265258

  6. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Qiaoyuan [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Xu, Enwu [Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People' s Liberation Army, Guangzhou 510010 (China); Dai, Jiabin; Liu, Binbin; Han, Zhiyuan; Wu, Jianjun; Zhang, Shaozhu; Peng, Baoying [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou 510182 (China); Jiang, Yiguo, E-mail: jiangyiguo@vip.163.com [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China)

    2015-06-01

    Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G{sub 0}/G{sub 1} in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol.

  7. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

    International Nuclear Information System (INIS)

    Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G0/G1 in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol

  8. Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary

    Directory of Open Access Journals (Sweden)

    Morita Yoshihiro

    2012-02-01

    Full Text Available Abstract Background Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins have been identified as targets of resveratrol. Sirtuin 1 (SIRT1, originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary. Methods The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining. Results SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol

  9. Resveratrol cocrystals with enhanced solubility and tabletability.

    Science.gov (United States)

    Zhou, Zhengzheng; Li, Wanying; Sun, Wei-Jhe; Lu, Tongbu; Tong, Henry H Y; Sun, Changquan Calvin; Zheng, Ying

    2016-07-25

    Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development. PMID:27282539

  10. Resveratrol inhibits LPS-induced MAPKs activation via activation of the phosphatidylinositol 3-kinase pathway in murine RAW 264.7 macrophage cells.

    Directory of Open Access Journals (Sweden)

    Yi Zong

    Full Text Available BACKGROUND: Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect RAW 264.7 cells from inflammatory insults and explored mechanisms underlying inhibitory effects of resveratrol on RAW 264.7 cells. METHODOLOGY/PRINCIPAL FINDINGS: Murine RAW 264.7 cells were treated with resveratrol (1, 5, and 10 µM and/or LPS (5 µg/ml. Nitric oxide (NO and prostaglandin E2 (PGE2 were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by ELISA, RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of Akt, cyclic AMP-responsive element-binding protein (CREB, mitogen-activated protein kinases (MAPKs cascades, AMP-activated protein kinase (AMPK and expression of SIRT1(Silent information regulator T1 were measured by western blot. Wortmannin (1 µM, a specific phosphatidylinositol 3-kinase (PI3-K inhibitor, was used to determine if PI3-K/Akt signaling pathway might be involved in resveratrol's action on RAW 264.7 cells. Resveratrol significantly attenuated the LPS-induced expression of nitric oxide (NO, prostaglandin E2 (PGE2, inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in RAW 264.7 cells. Resveratrol increased Akt phosphorylation in a time-dependent manner. Wortmannin, a specific phosphatidylinositol 3-kinase (PI3-K inhibitor, blocked the effects of resveratrol on LPS-induced RAW 264.7 cells activation. In addition, PI3-K inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of cyclic AMP-responsive element-binding protein (CREB and mitogen-activated protein kinases (MAPKs cascades. Meanwhile, PI3-K is essential for resveratrol-mediated phosphorylation of AMPK and expression of SIRT1. CONCLUSION AND IMPLICATIONS: This investigation

  11. The Effect of Sulfated (1→3-α-l-Fucan from the Brown Alga Saccharina cichorioides Miyabe on Resveratrol-Induced Apoptosis in Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Olesia S. Vishchuk

    2013-01-01

    Full Text Available Accumulating data clearly indicate that the induction of apoptosis by nontoxic natural compounds is a potent defense against the development and progression of many malignancies, including colon cancer. Resveratrol and the fucoidans have been shown to possess potent anti-tumor activity in vitro and in vivo. The aim of the present study was to examine whether the combination of a fucoidan from the brown alga Saccharina cichorioides Miyabe and resveratrol would be an effective preventive and/or therapeutic strategy against colon cancer. Based on NMR spectroscopy and MALDI-TOF analysis, the fucoidan isolated and purified from Saccharina cichorioides Miyabe was (1→3-α-l-fucan with sulfate groups at C2 and C4 of the α-l-fucopyranose residues. The fucoidan enhanced the antiproliferative activity of resveratrol at nontoxic doses and facilitated resveratrol-induced apoptosis in the HCT 116 human colon cancer cell line. Apoptosis was realized by the activation of initiator caspase-9 and effector caspase-7 and -3, followed by the cleavage of PARP. Furthermore, significant inhibition of HCT 116 colony formation was associated with the sensitization of cells to resveratrol by the fucoidan. Taken together, these results demonstrate that the combination of the algal fucoidan with resveratrol may provide a potential therapy against human colon cancer.

  12. Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors

    Directory of Open Access Journals (Sweden)

    Qing Liu

    2015-09-01

    Full Text Available Resveratrol (1, a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore, resveratrol derivatives were prepared to improve bioavailability and anti-melanogenesis activity. Nine resveratrol derivatives including five alkyl ether derivatives with C2H5, C4H9, C5H11, C6H13, and C8H17 (2a–2e and four ester derivatives with CH3, CH=C(CH32, CH(C2H5C4H9, C7H15 (3a–3d were newly synthesized and their effect on melanin synthesis were assessed. All the synthetic derivatives efficiently reduced the melanin content in α-MSH stimulated B16F10 melanoma cells. Further investigation showed that the inhibitory effect of 2a on melanin synthesis was achieved not by the inhibition of tyrosinase activity but by the inhibition of melanogenic enzyme expressions such as tyrosinase and tyrosinase-related protein (TRP-1. Our synthetic resveratrol derivatives have more lipophilic properties than resveratrol by the addition of alkyl or acyl chains to free hydroxyl moiety of resveratrol; thus, they are expected to show better bioavailability in skin application. Therefore, we suggest that our synthetic resveratrol derivatives might be promising candidates for better practical application to skin-whitening cosmetics.

  13. Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    William L Riles; Jason Erickson; Sanjay Nayyar; Mary Jo Atten; Bashar M Attar; Oksana Holian

    2006-01-01

    AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-Ⅲ) with deleted p53.METHODS: Nuclear fragmentation was used to quantitate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression.RESULTS: Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP, Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bclxl, Bax, Bid or Smac/Diablo, and did not promote subcellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines.SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-Ⅲ cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities.CONCLUSION: These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells.

  14. Resveratrol preserves cerebrovascular density and cognitive function in aging mice

    NARCIS (Netherlands)

    Oomen, Charlotte A.; Farkas, Eszter; Roman, Viktor; van der Beek, Eline M.; Luiten, Paul G. M.; Meerlo, Peter

    2009-01-01

    Resveratrol, a natural polyphenol abundant in grapes and red wine, has been reported to exert numerous beneficial health effects. Among others, acute neuroprotective effects of resveratrol have been described in several models of neurodegeneration, both in vitro and in vivo. In the present study we

  15. Probing the position of resveratrol in lipid bilayers

    DEFF Research Database (Denmark)

    de Ghellinck, Alexis; Shen, Chen; Fragneto, Giovanna;

    2015-01-01

    orientation and leading to a reduction of the projected area per headgroup. This effect is propagated into the hydrophobic core, where the chain packing is modified despite the absence of resveratrol. When interacting with a DPPC/cholesterol membrane, resveratrol has a similar effect on the neighboring PC...

  16. Resveratrol in the treatment of diabetes mellitus%白藜芦醇与糖尿病关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨菊红; 王楠; 冯凭

    2009-01-01

    Resveratrol (3,5,4-trihydroxystilbene), a naturally occurring phytoalexin found in juice and red wines, has been reported to exert a variety beneficial effects on the pathogenesis of atherosclerosis. Recently, resveratrol has been found in a dose-dependent manner lowering of the plasma glucose and lipid concentrations, and can also ameliorate the common diabetes mellitus symptoms. The mechanisms may attribute to its anti-oxidative and anti-inflammatory properties, and in many experimental systems, resveratrol has also been found to be a modulator of insulin secretion. Those effects of resveratrol may depend on the activation of SIRT1, but resveratrol may also function in a SIRT1-non-depentent manner. Further investigation of the roles of resveratrol may provide a new direction in the treatment of diabetes mellitus.%白藜芦醇属于一种酚类植物抗毒素,是天然的抗氧化物和自由基廓清剂.近期研究发现,白藜芦醇除具有抗动脉粥样硬化的作用外,还具有明显的降低血糖,改善糖尿病的作用.其机制与抗氧化应激、抗炎性反应、改善胰岛素敏感性、改善胰岛素分泌等有关.白藜芦醇的上述作用可能与其激活组蛋白去乙酰化酶(SIRT)1有关,也可能还有其他非SIRT1依赖机制.因此,对白藜芦醇改善糖尿病作用的深入研究可能为研究新型降糖药物开辟新的方向.

  17. Pre-formulation characterization and pharmacokinetic evaluation of resveratrol

    Science.gov (United States)

    Robinson-Barnes, Keila Delores

    Resveratrol, a natural compound found in grapes has potential chemotherapy effects but very low oral bioavailability in humans. The objectives of this study are to quantitatively characterized and understand the physiochemical properties and the pharmacokinetic evaluation of resveratrol. Solubility of resveratrol was measured in 10 common solvents at 25°C using HPLC. The solution state pH stability of resveratrol was assessed in various USP buffers ranging from pH 2-10 for 24 hours at 37 °C. Human plasma protein binding was determined using ultracentrifugation technique. Stability of resveratrol in human and rat plasma was also assessed at 37°C. Aliquots of blank plasma were spiked with a standard drug concentration to yield final plasma concentration of 50 mug/mL. Samples were analyzed for resveratrol concentration up to 96 hours. A group (n=8) of jugular vein-cannulated adult male Sprague-Dawley rats were evaluated and received intravenous dose of 20 mg/kg resveratrol. Serial blood samples were collected up to 8 hours after the dose. Plasma concentrations of resveratrol were measured by an established LC-MS/MS method. Pharmacokinetic parameters were assessed using noncompartmental methods. Resveratrol is more soluble in alcohol and PEG-400, and stable in acidic pH. It binds highly to plasma proteins, and degrades slower in human then rat plasma. Resveratrol exhibits bioexponential disposition after intravenous administration and has a short elimination half-life. Resveratrol displays bioexponential disposition following intravenous administration. The estimated mean maximum concentration was 1045.5 ng/mL and rapidly dropped below 100 ng/mL within 30 minutes. The area under the concentration time curve (AUC) for resveratrol was 13888.7 min*ng/mL The mean terminal elimination half-life was 50.9 minutes. The mean total body clearance (Cl) and volume of distribution of trans-resveratrol were 1711.9mL/min/kg and 91087.8 mL/kg, respectively. Pre

  18. Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

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    Seyed Jalal Hosseinimehr

    2014-01-01

    Full Text Available Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2 were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy.

  19. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 μM) for 24 hr induced...

  20. Alternaria sp. MG1, a resveratrol-producing fungus: isolation, identification, and optimal cultivation conditions for resveratrol production

    Science.gov (United States)

    Due to its potential in preventing or slowing the occurrence of many diseases, resveratrol (3,5,4-trihydroxystilbene) has attracted great research interest. The objective of this study was to identify the microorganisms that possess resveratrol producing capability from selected plants and optimize ...

  1. Antimyeloma effects of resveratrol through inhibition of angiogenesis

    Institute of Scientific and Technical Information of China (English)

    HU Yu; SUN Chun-yan; HUANG Jing; HONG Liu; ZHANG Lu; CHU Zhang-bo

    2007-01-01

    Background In multiple myeloma (MM), bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells.Methods RPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25-50.00 μmol/L) for different times (12-72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases (MMP)-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA).Results Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity.Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore,decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression.Conclusions Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF,bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.

  2. Protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat

    Institute of Scientific and Technical Information of China (English)

    Hong-Min Wang; Guo-Xing Li; Han-Song Zheng; Xue-Zhi Wu

    2015-01-01

    Objective:To study the protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat.Methods:A total of84Wistar rats were divided into4 groups:12 inGroupA(control group),24 inGroupB(diabetic cataract group),24 inGroupC(therapeutic-dose of resveratrol group) and24 inGroupD(low-dose of resveratrol group).Rats inGroupB-D were given with 60 mg/kg streptozotocin through intraperitoneal injection.Rats inGroupC were given with100 mg/kg resveratrol and rats inGroupD were given with20 mg/kg resveratrol.The caspase-3 expression levels and apoptosis ratios ofLEC among each group were observed; the degrees of lens opacity inGroupB-D after12 weeks were compared.Results:There were significant differences in caspase-3 expression levels, apoptosis ratios ofLEC among groups at4 w,8 w and 12 w(P<0.05).After12 weeks, inGroupB the degree of lens opacity was as follow:0(0.00%) in grade Ⅰ,3(37.50%) in gradeⅡ,2(25.00%)in grade Ⅲ,2(25.00%)grade Ⅳ, and1(12.50%) in grade Ⅴ; inGroupC:2(25.00%)in grade Ⅰ,4(50.00%) in gradeⅡ,2(25.00%)in grade Ⅲ,0(0.00%)grade Ⅳ, and0(0.00%) in grade Ⅴ; inGroupD:1(12.50%)in grade Ⅰ,4(50.00%) in gradeⅡ,2(25.00%) in grade Ⅲ,1(12.50%) grade Ⅳ, and0(0.00%) in grade Ⅴ.The difference amongGroupB-D was statistically significant(P<0.05).Conclusions:Resveratrol has protective effect on lens epithelial cell apoptosis in diabetic cataract rat, and the effect is relative to its dose.

  3. Modulation of Akt and ERK1/2 pathways by resveratrol in chronic myelogenous leukemia (CML cells results in the downregulation of Hsp70.

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    Soumyajit Banerjee Mustafi

    Full Text Available BACKGROUND: Resveratrol is known to downregulate the high endogenous level of Heat shock protein 70 (Hsp70 in Chronic Myelogenous Leukemia (CML K562 cells and induce apoptosis. Since Heat Shock Factor 1 (HSF1 controls transcription of Hsp70, we wanted to probe the signaling pathways responsible for transcriptional activation of HSF1. METHODOLOGY/PRINCIPAL FINDINGS: Cells exposed to 40microM Resveratrol rapidly abolished serine473 phosphorylation of Akt and significantly reduced its kinase activity. Inactivation of Akt pathway by Resveratrol subsequently blocked serine9 phosphorylation of Gsk3beta. Active non-phosphorylated Gsk3beta rendered HSF1 transcriptionally inactive and reduced Hsp70 production. Blocking PI3K/Akt activity also demonstrated similar effects on Hsp70 comparable to Resveratrol. Inactivation of Gsk3beta activity by inhibitors SB261763 or LiCl upregulated Hsp70. Resveratrol significantly modulated ERK1/2 activity as evident from hyper phosphorylation at T302/Y304 residues and simultaneous upregulation in kinase activity. Blocking ERK1/2 activation resulted in induction of Hsp70. Therefore, increase in ERK1/2 activity by Resveratrol provided another negative influence on Hsp70 levels through negative regulation of HSF1 activity. 17-allylamino-17-demethoxygeldanamycin (17AAG, a drug that inhibits Hsp90 chaperone and degrades its client protein Akt concomitantly elevated Hsp70 levels by promoting nuclear translocation of HSF1 from the cytosol. This effect is predominantly due to inhibition of both Akt and ERK1/2 activation by 17AAG. Simultaneously treating K562 with Resveratrol and 17AAG maintained phosho-ERK1/2 levels close to untreated controls demonstrating their opposite effects on ERK1/2 pathway. Resveratrol was found not to interfere with Bcr-Abl activation in K562 cells. CONCLUSION/SIGNIFICANCE: Thus our study comprehensively illustrates that Resveratrol acts downstream of Bcr-Abl and inhibits Akt activity but stimulates ERK

  4. Function of resveratrol de- rived from transgenic plant expressing resveratrol synthase gene

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Two genes from grapevine coding for resveratrol synthase, named RS1 and RS2, were cloned by RT-PCR. An Escherichia coli expression vector was constructed by insertion of RS1 into pBV221. A specific protein with the same molecular weight (42 ku) as the resveratrol synthase was expressed and used to prepare the rabbit antiserum. A plant expression vector was constructed by inserting the RS1 gene into pBin438 downstream of the doubled CaMV 35S promoter and TMV-W fragment. PCR-positive transgenic tobacco plants were obtained after transformation with Agrobacterium tumefaciens LBA4404 harboring the plant expression vector. Southern blot analysis demonstrated that the foreign gene was integrated into the tobacco genome. The results of RT-PCR and Western blot indicated that the RS1 gene was transcribed and expressed. Formation of resvera-trol in transgenic tobacco was further determined by thin-layer chromatography of silica gel and HPLC. Increased accumulation of human breast adenocarcinoma cells in G0 and G1 phases of cell cycle was observed in cells treated with resveratrol purified from transgenic tobacco as compared to the untreated cells.

  5. Plant derived antioxidants and antifibrotic drugs: past, present and future

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    Devaraj Ezhilarasan

    2014-09-01

    Full Text Available Hepatic fibrosis occurs as a wound-healing process after several forms of chronic hepatic injury. Activation and proliferation of hepatic stellate cells play pivotal role in the pathogenesis of hepatic fibrosis. Many researchers, from the therapeutic perspective, have focused their attention on searching for novel agents with inhibitory effects on hepatic stellate cells proliferation and activation to prevent hepatic fibrogenesis and a number of plant derived antioxidants have been tested as anti-fibrogenic agents, they generally suppress proliferation and collagen synthesis. Plants remain an imperative source of novel drugs, novel drug leads and new chemical entities. The plant based drug discovery resulted primarily in the development of antioxidant, anti-cancer and other anti-infectious agents and continues to contribute to the new leads in clinical trials. This review summarizes some of those most important plant derived anti-fibrotic drugs and their beneficial effects on experimentally induced hepatic fibrosis in vitro and in vivo. The plant derived antioxidant compounds described herein are curcumin, silymarin, silibinin, baicalein, resveratrol, salvianolic acids, tetrandine, quercetin and berberine. Studies from ours and as demonstrated by pervious workers much information has been accumulated over the past two decades through in vivo and in vitro. In light of those studies, it has been confirmed that plants derived antioxidants, particularly flavanoids, show a significant influence to block hepatic fibrosis regardless of any etiology. This review outlines recent progress in the use of plant derived drugs against experimentally induced liver fibrosis by in vitro and in vivo studies and summarizes the possible mechanisms anti-fibrotic effects of these compounds.

  6. Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis.

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    Anshoo Malhotra

    Full Text Available BACKGROUND: The combination approach is the future of the war against cancer and the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol during lung carcinogenesis. METHODS: The mice were segregated into five groups which included normal control, Benzo[a]pyrene[BP] treated, BP+curcumin treated, BP+resveratrol treated and BP+curcumin+resveratrol treated. RESULTS: The morphological analyses of tumor nodules confirmed lung carcinogenesis in mice after 22 weeks of single intra-peritoneal[i.p] injection of BP at a dose of 100 mg/Kg body weight. The BP treatment resulted in a significant increase in the protein expressions of p53 in the BP treated mice. Also, a significant increase in the protein expression of phosphorylated p53[ser15] confirmed p53 hyper-phosphorylation in BP treated mice. On the other hand, enzyme activities of caspase 3 and caspase 9 were noticed to be significantly decreased following BP treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the lung slices of BP treated mice. Moreover, a significant rise in the cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the lung slices of BP treated mice. Interestingly, combined treatment of curcumin and resveratrol to BP treated animals resulted in a significant decrease in p53 hyper-phosphorylation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the BP treated mice. However, the enzyme activities of caspase 3 and caspase 9 showed a significant increase upon treatment with curcumin and resveratrol. CONCLUSION: The study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes.

  7. Protective Effect of N-Acetylcystein and Resveratrol on Ischemia-Reperfusion Injury in Rat Ovary

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    Avni Kılıç

    2016-06-01

    Full Text Available Objective: The aim of this study is evaluating the protective activity of N-acetyl cysteine and resveratrol treatment against ischemia - reperfusion damage created experimentally in rat ovaries. Methods: 42 female Wistar rats were used in our study. Rats were separated randomly into six groups consisting of seven rats as sham, torsion, torsion- detorsion, torsion-detorsion+saline, torsion-detorsion+resveretrol (20 mg/kg and torsion- detorsion+N-acetyl cysteine (150 mg/kg. Except Sham, ovarian torsion procedure was implemented to all other groups for 2 hours. Detorsion procedure was implemented to other groups for 2 hours, except the torsion group. Medications were given through intraperitoneal way half an hour before the detorsion procedure in saline (two milliliter, resveratrol (20 mg/kg and N-acetyl cysteine (150 mg/kg groups. Then, 2 ml of blood samples were drawn for markers of oxidative stress and tumour necrosis factor-alpha (TNF-α work and the ovaries, which were torsioned for the histologic examination, were ex­tracted from all rats. Edema, congestion, hemorrhage, leuko­cyte infiltration and degeneration of follicles were evaluated by histopathological examination. Results: According to histopathologic damage scores, the least damage was seen in sham group and the most damage was seen T-DT group (1.00±0.81 vs. 11.00±1.15, respectively; p<0.001. It was seen that resveratrol and N-acetyl cysteine treatments were effective in decreasing tissue damage (total damage score average 83.85±0.89 vs. 3.85±0.89, respec­tively; p<0.001, and on the other hand there was not any dif­ference between resveratrol and N-acetyl cysteine treatments (p=0.966. Besides, it was determined that oxidative stress levels were higher in torsion - detorsion group and the resve­ratrol and N-acetyl cysteine treatment caused a significant de­crease in oxidative stress levels. In additionally, the reductions of TNF-α levels were found to be equally effective in

  8. Resveratrol reestablishes spermatogenesis after testicular injury in rats caused by 2,5-hexanedione

    Institute of Scientific and Technical Information of China (English)

    JIANG Yong-guang; PENG Tao; LUO Yong; LI Ming-chuan; LIN Yun-hua

    2008-01-01

    Background Environmental toxins can destroy the physiological process of spermatogenesis and even lead to male infertility.Resveratrol(RES)is a natural phytoalexin with a wide range of biological activities.Some recent researches have demonstrated that RES can increase sperm output and protect sperm from apoptosis caused by physical damage.However,there is no evidence indicating that it can also exhibit a similar activity in testis injury caused by environmental toxins.This study was designed to evaluate the protective effect of resveratrol on testis damaged by environmental toxins and to elucidate the possible mechanism of its protective effect.Methods In this study 2,5-hexanedione(2,5-HD)was used as the injury agent.Forty male SD rats were randomly divided into 5 groups.During the first 5 weeks,group A was raised normally,groups B,C,D and E were exposed to 1% 2,5-HD;during the following 9 weeks,group C,D,E received intragastric administration of different concentrations of carboxymethylcellulose.Physical signs,body weight gain and testis weight were comparatively obsewed.Numbers and diameters of seminiferous tubules were analyzed following HE staining.In addition,expression of the c-kit protein and gene in spermatogenic cells jn every group was detected with immunohistochemistry,Western blot or RT-PCR.Results The 2,5-HD treatment resulted in physical signs that became worse and in emarciated testis.HE staining and immunohistochemistry showed that seminiferous tubules became emarcid,obsolete spermatogonia being stagnant and expression of c-kit protein being depressed.After oral administration of resveratrol,the 2,5-HD.induced physical signs were improved and close to the normal rats.The gain of body weight increased(P<0.01).The recovery of testis weight was significant(P<0.01).At the histological level,the seminiferous epithelia began to differentiate(P<0.01):and even the physiological process of spermatogenesis restarted.Moreover,expression of c-kit protein

  9. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia.

    Science.gov (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O

    2016-01-01

    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID:27574767

  10. Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

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    Brigitte Gonthier

    2012-01-01

    Full Text Available Aims. 3,5,4′-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10 μM slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100 μM enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol.

  11. Metabolic benefits of inhibiting cAMP-PDEs with resveratrol.

    Science.gov (United States)

    Chung, Jay H

    2012-10-01

    Calorie restriction (CR) extends lifespan in species ranging from yeast to mammals. There is evidence that CR also protects against aging-related diseases in non-human primates. This has led to an intense interest in the development of CR-mimetics to harness the beneficial effects of CR to treat aging-related diseases. One CR-mimetic that has received a great deal of attention is resveratrol. Resveratrol extends the lifespan of obese mice and protects against obesity-related diseases such as type 2 diabetes. The specific mechanism of resveratrol action has been difficult to elucidate because resveratrol has a promiscuous target profile. A recent finding indicates that the metabolic effects of resveratrol may result from competitive inhibition of cAMP-degrading phosphodiesterases (PDEs), which increases cAMP levels. The cAMP-dependent pathways activate AMP-activated protein kinase (AMPK), which is essential for the metabolic effects of resveratrol. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including protection against diet-induced obesity and an increase in mitochondrial function, physical stamina and glucose tolerance in mice. This discovery suggests that PDE inhibitors may be useful for treating metabolic diseases associated with aging. PMID:23700542

  12. Whole-body cryostimulation--potential beneficial treatment for improving antioxidant capacity in healthy men--significance of the number of sessions.

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    Anna Lubkowska

    Full Text Available It is claimed that WBC (whole-body cryotherapy enhances the resistance of the human body, also thanks to the beneficial effect on the antioxidant system. Accordingly, this research aimed to evaluate the effect of a series of whole-body cryostimulations on the level of non-enzymatic antioxidants and the activity of antioxidant enzymes in healthy men. The study was carried out on 30 young and healthy men aged 27.8±6.1 years with average body mass index and peak oxygen consumption (46.34±6.15 ml kg(-1 •min(-1. The participants were daily exposed for 3 minutes to cryogenic temperatures (-130°C. Blood samples were obtained in the morning before cryostimulation, again 30 min after exposure and the following day in the morning, during the 1(st, 10(th and 20(th session. Analysis concerned changes in plasma concentrations of total protein, albumin, glucose, uric acid and ceruloplasmin, and the most important components of the antioxidant system in red blood cells: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced and oxidized glutathione. To assess the oxidative stress level the 8-isoprostane concentration in plasma was measured. The obtained results indicate that cryogenic temperatures in repeated daily treatments result in changes in the peroxidant and antioxidant status. These changes seem to depend on the number of cryostimulations. After 20 daily treatments there was an increase in SOD, SOD:CAT ratio, a decrease in the concentration of reduced and oxidized glutathione and in the activity of GPx. It could be possible that differences in the activity of GSSG-R after 20 treatments depended on the body mass index of participants.

  13. High value co-products from wine byproducts (II): polyphenols and antioxidant activity

    Energy Technology Data Exchange (ETDEWEB)

    Femenia, A.; Gonzalez-Centeno, M. R.; Garau, M. C.; Sastre-Serrano, G.; Rosello, C.

    2009-07-01

    The by-products of the grape/wine industry have recently attracted considerable interest as important sources of high-value antioxidants. these can be extracted from stems, such as resveratrol,and from grape pomace which contains polyphenols, procyanidin and antrocyanins. (Author)

  14. Triple antioxidant SNEDDS formulation with enhanced oral bioavailability: Implication of chemoprevention of breast cancer.

    Science.gov (United States)

    Tripathi, Shailja; Kushwah, Varun; Thanki, Kaushik; Jain, Sanyog

    2016-08-01

    The present study aimed to develop quercetin, resveratrol and genistein loaded self-nanoemulsifying drug delivery system (SNEDDS) by QbD approach in order to improve their oral bioavailability and antioxidant potential. The size and PDI of the optimized formulation were found to be curve (AUC) of all three antioxidants. The SNEDDS demonstrated ~4.27 fold enhancement in oral bioavailability of quercetin, ~1.5 fold in case of resveratrol and ~2.8 fold in case of genistein as compared to free antioxidants suspension. Finally, the prophylactic antitumor efficacy of developed formulation was tested against DMBA induced breast cancer model in rats, which demonstrated enhanced abeyance towards the tumor growth as compared to free antioxidants. PMID:27033463

  15. The Immunomodulation Effect of Aronia Extract Lacks Association with Its Antioxidant Anthocyanins

    DEFF Research Database (Denmark)

    Mojsoska, Biljana; Xu, Jin

    2013-01-01

    Polyphenols comprise a diverse group of molecules with antioxidative and anti-inflammatory activities. To compare the antioxidative and anti-inflammatory capacity of Aronia melanocarpa berries (chokeberries), recognized for their high content of anthocyanins, a noncytotoxic isolation method...... was developed to obtain high-purity anthocyanins in the extract. The antioxidative activity of the extract, the anthocyanin-rich fraction (AF) was determined by 1,1-diphenyl-2-picrylhydrazyl radical and ferric-reducing ability of plasma along with resveratrol as a reference. The immunomodulation properties were......, whereas AF only had a slight effect in reducing IL-10. These results demonstrated that there was no major relationship between the antioxidative effect and immunomodulation capacities of AF and resveratrol. The immunomodulatory activity of the extract is associated with bioactive compounds in Aronia other...

  16. Occurrence and Estimation of trans-Resveratrol in One-Year-Old Canes from Seven Major Chinese Grape Producing Regions

    Directory of Open Access Journals (Sweden)

    Zhenwen Zhang

    2011-03-01

    Full Text Available The concentration of trans-resveratrol in 165 grape cane samples from three major grape production regions and four large distribution centers of Chinese wild Vitis species were determined by reversed-phase high-performance liquid chromatography (HPLC. Among the different genotype groups and purpose of uses, cultivars of V. vinifera had much higher amounts of trans-resveratrol than did the cultivars of both V. labrusca or V. labrusca and V. vinifera hybrids, and within the V. vinifera species, significantly higher amounts of trans-resveratrol were found in wine grapes compared to table ones. No significant differences were observed between V. labrusca and its hybrids from crosses with V. vinifera, and between red cultivars and white ones (P < 0.05 or P < 0.01. The contents of trans-resveratrol, as a normal constituent occurring in grape canes, in Chinese wild species of V. amurensis, V. pentagona, and V. davidii from their native habitats were also relatively high.

  17. Picea mariana bark: a new source of trans-resveratrol and other bioactive polyphenols.

    Science.gov (United States)

    García-Pérez, Martha-Estrella; Royer, Mariana; Herbette, Gaëtan; Desjardins, Yves; Pouliot, Roxane; Stevanovic, Tatjana

    2012-12-01

    The ethyl acetate soluble fraction obtained from the hot water extract of Picea mariana bark (BS-EAc(f)) has been demonstrated to have anti-inflammatory and antioxidant properties. Thus, in the current study, we isolated and characterised major compounds of this fraction by HPLC, NMR and MS analyses. On the whole, 28 compounds were identified, among which were five neolignans, seven lignans, trans-resveratrol, three phenolic acids and four flavonoids. To the best of our knowledge, 2,3-dihydro-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-(2S,3S)-1,4-benzodioxin-6-propanol, threo and erythro 3-methoxy-8,4'-oxyneolignan-3',4,7,9,9'-pentol, pallasiin, (±) epi-taxifolin, homovanillyl alcohol, orcinol and 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol are reported for the first time in the Picea genus. P. mariana dry bark contains at least 104μgg(-1)dw of trans-resveratrol and it could be therefore considered as a new accessible source of this molecule. This study provides novel information about the identity of major compounds present in BS-EAc(f), which is essential for the understanding of the anti-inflammatory and nutraceutical potential of this extract. PMID:22953840

  18. Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma

    Directory of Open Access Journals (Sweden)

    Caroline eMenard

    2013-12-01

    Full Text Available Polyphenols such as epigallocatechin gallate (EGCG and resveratrol have received a great deal of attention because they may contribute to the purported neuroprotective action of the regular consumption of green tea and red wine. Many studies, including those published by our group, suggest that this protective action includes their abilities to prevent the neurotoxic effects of beta-amyloid, a protein whose accumulation likely plays a pivotal role in Alzheimer’s disease. Moreover, the scavenging activities of polyphenols on reactive oxygen species and their inhibitory action of cyclooxygenase likely explain, at least in part, their antioxidant and anti-inflammatory activities. Besides these well-documented properties, the modulatory action of these polyphenols on intracellular signaling pathways related to cell death/survival (e.g. protein kinase C, PKC has yet to be investigated in detail. Using rat hippocampal neuronal cells, we aimed to investigate here the effects of EGCG and resveratrol on cell death induced by GF 109203X, a selective inhibitor of PKC. The MTT/resazurin and spectrin assays indicated that EGCG and resveratrol protected against GF 109203X-induced cell death and cytoskeleton degeneration, with a maximal effect at 1 and 3 µM, respectively. Moreover, immunofluorescence data revealed that cells treated with these polyphenols increased PKC gamma (g activation and promoted neuronal interconnections. Finally, we found that the protective effects of both polyphenols on the cytoskeleton and synaptic plasticity were mediated by the PKCg subunit. Taken together, the results suggest that PKC, and more specifically its g subunit, plays a critical role in the protective action of EGCG and resveratrol on neuronal integrity.

  19. Effect of Resveratrol on Preventing Steroid-induced Osteonecrosis in a Rabbit Model

    Institute of Scientific and Technical Information of China (English)

    Ji-Liang Zhai; Xi-Sheng Weng; Zhi-Hong Wu; Shi-Gong Guo

    2016-01-01

    Background:Prevention of osteonecrosis (ON) has seldom been addressed.The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits.Methods:Seventy-two rabbits were divided into four groups:(1) NEC (ON) group:thirty rabbits were treated with lipopolysaccharide (LPS) once,then with methylprednisolone (MPS) daily for 3 days;(2) PRE (prevention) group:thirty rabbits were given one dose of LPS,then MPS daily for 3 days,and resveratrol on day 0 and daily for 2 weeks;(3) RES (resveratrol) group:six rabbits were given resveratrol for 2 weeks but without LPS/MPS;(4) CON (control) group:six rabbits were given alcohol for 2 weeks but without LPS/MPS.Levels of plasma tissue-type plasminogen activator (t-PA),plasminogen activator inhibitor 1 (PAI-1),thrombomodulin (TM),vascular endothelial growth factor (VEGF),maximum enhancement (ME) by magnetic resonance imaging,and ON incidence were evaluated.Results:The PRE group had a lower ON incidence than the NEC group,but with no significant differences at 2 weeks and 12 weeks.The RES and CON groups did not develop ON.TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1,2,and 4 (TM:1 week,P =0.029;2 weeks,P =0.005;and 4 weeks,P =0.047;VEGF:1 week,P =0.039;2 weeks,P =0.021;4 weeks,P =0.014),but the difference disappeared at 12 weeks.The levels of t-PA and PAl-1 were not significantly different between the NEC and PRE groups.The TM,t-PA,PAI-l,and VEGF concentrations in the RES and CON groups did not change over time.Compared to the baseline,ME in the NEC group decreased significantly (P =0.025) at week 1,increased significantly (P =0.021) at week 2,and was decreased at week 12.The variance was insignificant in the PRE group.Conclusions:Resveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti-inflammatory effects to protect the vascular endothelium and reduce thrombosis.

  20. Garlic and Resveratrol Attenuate Diabetic Complications, Loss of β-Cells, Pancreatic and Hepatic Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Kaur, Gagandeep; Padiya, Raju; Adela, Ramu; Putcha, Uday K.; Reddy, G. S.; Reddy, B. R.; Kumar, K. P.; Chakravarty, Sumana; Banerjee, Sanjay K.

    2016-01-01

    The study was aimed at finding the effect of garlic and resveratrol on loss of β-cells and diabetic complication in streptozotocin (STZ)-induced Type-I diabetic rats. Rats were injected with single dose STZ (50 mg/kg, i.p.) for induction of type 1 diabetes (Dia) and compared with control group. Rats from third (Dia+Gar), fourth (Dia+Resv), and fifth (Dia+Met) groups were fed raw garlic homogenate (250 mg/kg/day), resveratrol (25 mg/kg/day), and metformin (500 mg/kg/day) orally, respectively, for a period of 4 weeks. Diabetic group had decreased serum insulin and hydrogen sulfide levels along with increased blood glucose and glycated hemoglobin, triglyceride, uric acid, and nitric oxide levels. Significant (p < 0.05) increase in pancreatic and hepatic TBARS, conjugated dienes, nitric oxide, and AGE level and significant (p < 0.05) decrease in SOD, catalase, H2S, GSH level were observed in diabetic group. Administration of garlic, resveratrol, and metformin significantly (p < 0.05) normalized most of the altered metabolic and oxidative stress parameters as well as histopathological changes. Administration of garlic, resveratrol, and metformin in diabetic rat decreases pancreatic β-cell damage and hepatic injury. Our data concluded that administration of garlic showed more promising effect in terms of reducing oxidative stress and pathological changes when compared to resveratrol and metformin groups.

  1. Resveratrol inhibits collagen I synthesis by suppressing IGF-1R activation in intestinal fibroblasts

    Science.gov (United States)

    Li, Ping; Liang, Mei-Lan; Zhu, Ying; Gong, Yao-Yao; Wang, Yun; Heng, Ding; Lin, Lin

    2014-01-01

    I induced by IGF-1. Moreover, silencing SIRT1 restored collagen I expression in fibroblasts challenged with resveratrol. However, disruption of SIRT1 did not influence the anti-fibrotic effects of resveratrol and IGF-1-induced collagen I expression. Further analysis revealed that resveratrol significantly decreased phosphorylation of IGF-1R and its downstream signaling molecules by inhibiting IGF-1 binding to its receptor. CONCLUSION: Our data suggest that resveratrol effectively inhibits collagen I synthesis in IGF-1-stimulated fibroblasts, partly by inhibiting IGF-1R activation, and SIRT1 is also responsible for the process. PMID:24782617

  2. Examining the Genomic Influence of Skin Antioxidants In Vitro

    OpenAIRE

    Gruber, James V.; Robert Holtz

    2010-01-01

    A series of well-known, purified antioxidants including: Resveratrol, Epigallocatechin Gallate (EGCG), Genistein, Rosavin, Puerarin, Chlorogenic Acid, Propolis and two newer unexplored isoflavonoids isolated from Maclura pomifera (Osage Orange) including Pomiferin and Osajin, were applied to Normal Human Dermal Fibroblasts (NHDF) and Normal Human Dermal Keratinocytes (NHEK) for 24 hours. The resulting treated cells were then examined using human gene microarrays supplied by Agilent. These c...

  3. Coadministration of Resveratrol and Rice Oil Mitigates Nociception and Oxidative State in a Mouse Fibromyalgia-Like Model

    Science.gov (United States)

    Peres Klein, Caroline; Rodrigues Cintra, Marcos; Binda, Nancy; Montijo Diniz, Danuza; Gomez, Marcus Vinicius; Souto, Andre Arigony; de Souza, Alessandra Hubner

    2016-01-01

    The mechanism underlying pain symptoms in fibromyalgia (FM) is not fully understood. Oxidative stress has emerged as pathophysiological event occurring during the development of the disease. The present study aimed at investigating the efficacy of resveratrol associated with rice bran oil on fibromyalgia-like mice model. Subcutaneous injection of reserpine (0.25 mg/Kg) during 3 days produced fibromyalgia-like symptoms. Resveratrol and/or rice oil or pregabalin were administered through oral route in therapeutic (single dose) and preventive (four doses) schemes. In both schemes, treatment with resveratrol associated with rice bran oil and pregabalin significantly reduced mechanical allodynia and thermal hyperalgesia in animals. The preventive scheme displayed antidepressant effect which was demonstrated by the forced swimming test as well as reduced reactive species in the cerebrospinal fluid of reserpinized animals. Taken together, our data provide evidences that the intake of resveratrol associated with rice bran oil plays antinociceptive and antidepressant actions probably through reducing reactive species and suggests the involvement of oxidative stress in this model of FM as possible underlying mechanism of pathogenesis of the disease. PMID:27069683

  4. Resveratrol Induces Apoptosis and Autophagy in T-cell Acute Lymphoblastic Leukemia Cells by Inhibiting Akt/mTOR and Activating p38-MAPK

    Institute of Scientific and Technical Information of China (English)

    GE Jiao; LIU Yan; LI Qiang; GUO Xia; GU Ling; MA Zhi Gui; ZHU Yi Ping

    2013-01-01

    Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.

  5. Interaction of dietary resveratrol with animal-associated bacteria.

    Science.gov (United States)

    Jung, Carina M; Heinze, Thomas M; Schnackenberg, Laura K; Mullis, Lisa B; Elkins, Stephanie A; Elkins, Christopher A; Steele, Roger S; Sutherland, John B

    2009-08-01

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antifungal phytoalexin produced by grapes, peanuts, and Japanese knotweeds, is thought to be a beneficial dietary phytochemical in red wine and grape juice. Information on its antibacterial properties and biotransformation, however, is limited. We surveyed the interactions of resveratrol with 43 strains of bacterial species that are often animal- or human-associated. Resveratrol at 50 mg L(-1) reduced the growth rates of most of the bacteria tested, but did not totally prevent growth even at much higher levels. Eleven of the 43 bacteria were capable of transforming at least 20% of the resveratrol. Three major metabolites were identified as resveratroloside, piceid, and dihydroresveratrol, and three other metabolites were partially characterized.

  6. Gnetuhainin S, a New Resveratrol Dimer from Gnetum hainanense

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Gnetuhainin S, a new resveratrol dimer, was isolated from the lianas of Gnetum hainanense C. Y. Cheng. Its structure and relative configuration were established on the basis of spectroscopic evidence.

  7. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Teng Ma

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

  8. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

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    Mamoru Takeda

    2016-10-01

    Full Text Available Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  9. Resveratrol plays important role in protective mechanisms in renal disease - mini-review

    Directory of Open Access Journals (Sweden)

    Guilherme Albertoni

    2015-03-01

    Full Text Available Resveratrol (RESV is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII and endothelin-1 (ET-1, as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

  10. Three New Resveratrol Derivatives from the Mangrove Endophytic Fungus Alternaria sp.

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    Jinhua Wang

    2014-05-01

    Full Text Available Three new resveratrol derivatives, namely, resveratrodehydes A–C (1–3, were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds showed broad-spectrum inhibitory activities against three human cancer cell lines including human breast MDA-MB-435, human liver HepG2, and human colon HCT-116 by MTT assay (IC50 < 50 μM. Among them, compounds 1 and 2 both exhibited marked cytotoxic activities against MDA-MB-435 and HCT-116 cell lines (IC50 < 10 μM. Additionally, compounds 1 and 3 showed moderate antioxidant activity by DPPH radical scavenging assay.

  11. Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds

    International Nuclear Information System (INIS)

    Numerous dietary compounds, ubiquitous in fruits, vegetables and spices have been isolated and evaluated during recent years for their therapeutic potential. These compounds include flavonoid and non-flavonoid polyphenols, which describe beneficial effects against a variety of ailments. The notion that these plant products have health promoting effects emerged because their intake was related to a reduced incidence of cancer, cardiovascular, neurological, respiratory, and age-related diseases. Exposure of the body to a stressful environment challenges cell survival and increases the risk of chronic disease developing. The polyphenols afford protection against various stress-induced toxicities through modulating intercellular cascades which inhibit inflammatory molecule synthesis, the formation of free radicals, nuclear damage and induce antioxidant enzyme expression. These responses have the potential to increase life expectancy. The present review article focuses on curcumin, resveratrol, and flavonoids and seeks to summarize their anti-inflammatory, cytoprotective and DNA-protective properties.

  12. Liver δ-Aminolevulinate Dehydratase Activity is Inhibited by Neonicotinoids and Restored by Antioxidant Agents

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    Elisa Sauer

    2014-11-01

    Full Text Available Neonicotinoids represent the most used class of insecticides worldwide, and their precursor, imidacloprid, is the most widely marketed. The aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ-aminolevulinate dehydratase (δ-ALA-D, protective effect of potential antioxidants against this potential effect and presence of chemical elements in the constitution of this pesticide. We observed that δ-ALA-D activity was significantly inhibited by imidacloprid at all concentrations tested in a dose-dependent manner. The IC50 value was obtained and used to evaluate the restoration of the enzymatic activity. δ-ALA-D inhibition was completely restored by addition of dithiotreitol (DTT and partly by ZnCl2, demonstrating that the inhibition occurs by oxidation of thiol groups and by displacement of the Zn (II, which can be explained by the presence of chemical elements found in the constitution of pesticides. Reduced glutathione (GSH had the best antioxidant effect against to δ-ALA-D inhibition caused by imidacloprid, followed by curcumin and resveratrol. It is well known that inhibition of the enzyme δ-ALA-D may result in accumulation of its neurotoxic substrate (δ-ALA, in this line, our results suggest that further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and the involvement of antioxidants in cases of poisoning by neonicotinoids.

  13. Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives.

    Science.gov (United States)

    Salomone, Federico; Godos, Justyna; Zelber-Sagi, Shira

    2016-01-01

    Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications. PMID:26436447

  14. Resveratrol: A Sirtuin Activator and The Fountain of Youth

    OpenAIRE

    Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya

    2015-01-01

    BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life. CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a const...

  15. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    OpenAIRE

    Nádia Rezende Barbosa Raposo; Adilson David da Silva; Raquel da Silva Teixeira; Gustavo Senra Gonçalves de Carvalho; Paula Rafaela Rocha; Danielle Cristina Zimmermann Franco

    2012-01-01

    Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory ac...

  16. Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.

    Directory of Open Access Journals (Sweden)

    Jasmine George

    Full Text Available Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01. This combination also significantly regressed tumor volume and number (p<0.01. Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15 in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.

  17. Resveratrol and calcium signaling: molecular mechanisms and clinical relevance.

    Science.gov (United States)

    McCalley, Audrey E; Kaja, Simon; Payne, Andrew J; Koulen, Peter

    2014-06-05

    Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol's mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol's actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  18. Resveratrol biosynthesis: plant metabolic engineering for nutritional improvement of food.

    Science.gov (United States)

    Giovinazzo, Giovanna; Ingrosso, Ilaria; Paradiso, Annalisa; De Gara, Laura; Santino, Angelo

    2012-09-01

    The plant polyphenol trans-resveratrol (3, 5, 4'-trihydroxystilbene) mainly found in grape, peanut and other few plants, displays a wide range of biological effects. Numerous in vitro studies have described various biological effects of resveratrol. In order to provide more information regarding absorption, metabolism, and bioavailability of resveratrol, various research approaches have been performed, including in vitro, ex vivo, and in vivo models. In recent years, the induction of resveratrol synthesis in plants which normally do not accumulate such polyphenol, has been successfully achieved by molecular engineering. In this context, the ectopic production of resveratrol has been reported to have positive effects both on plant resistance to biotic stress and the enhancement of the nutritional value of several widely consumed fruits and vegetables. The metabolic engineering of plants offers the opportunity to change the content of specific phytonutrients in plant - derived foods. This review focuses on the latest findings regarding on resveratrol bioproduction and its effects on the prevention of the major pathological conditions in man.

  19. Challenges in Analyzing the Biological Effects of Resveratrol

    DEFF Research Database (Denmark)

    Erdogan, Cihan Süleyman; Vang, Ole

    2016-01-01

    The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biolog......The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety...... research. Questions we address include: (1) Is the combinatorial effect of resveratrol and other compounds real? (2) What are the real and relevant doses of resveratrol after administration? and (3) Is it possible to estimate the preventive effect of resveratrol by clinical trials using standard...... experimental designs? The examples concerning resveratrol taken from the scientific literature are mainly from 2010 and later. The challenges pointed out in this review are similar to most naturally occurring bioactive compounds...

  20. A Novel Dietary Supplement Containing Multiple Phytochemicals and Vitamins Elevates Hepatorenal and Cardiac Antioxidant Enzymes in the Absence of Significant Serum Chemistry and Genomic Changes

    Directory of Open Access Journals (Sweden)

    Elida Bulku

    2010-01-01

    Full Text Available A novel dietary supplement composed of three well-known phytochemicals, namely, Salvia officinalis (sage extract, Camellia sinensis (oolong tea extract, and Paullinia cupana (guarana extract, and two prominent vitamins (thiamine and niacin was designed to provide nutritional support by enhancing metabolism and maintaining healthy weight and energy. The present study evaluated the safety of this dietary supplement (STG; S, sage; T, tea; G, guarana and assessed changes in target organ antioxidant enzymes (liver, kidneys and heart, serum chemistry profiles and organ histopathology in Fisher 344 rats. Adult male and female Fisher 344 rats were fed control (no STG or STG containing (1X and 7X, 1X = daily human dose diets and sacrificed after 2 and 4 months. Serum chemistry analysis and histopathological examination of three vital target organs disclosed no adverse influence on protein, lipid and carbohydrate profiles, genomic integrity of the liver and/or the tissue architecture. However, analysis of the most important antioxidant components in the liver, kidney and heart homogenates revealed a dramatic increase in total glutathione concentrations, glutathione peroxidase and superoxide dismutase enzyme activities. Concomitantly, oxidative stress levels (malondialdehyde accumulation in these three organs were less than control. Organ specific serum markers (ALT/AST for the liver; CPK/AST/LDH for the heart; BUN/creatinine for kidneys and the genomic integrity disclosed no STG-induced alteration. Some of the serum components (lipid and protein showed insignificant changes. Overall, STG-exposed rats were more active, and the results suggest that STG exposure produces normal serum chemistry coupled with elevated antioxidant capacity in rats fed up to seven times the normal human dose and does not adversely influence any of the vital target organs. Additionally, this study reiterates the potential benefits of exposure to a pharmacologically relevant

  1. Advances in Research of Resveratrol Analogs and Derivatives%白藜芦醇类似物及衍生物的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈笑; 金欣

    2015-01-01

    Recently, resveratrol has become the focus of attention of the global pharmaceutical sector for its an-tioxidant and anti-tumor biological activity. However, the low target selectivity, inefficacy and low bioavailability have become a major difficulty limiting resveratrol applications. Studies have shown that resveratrol derivatives and analogs synthesized from the lead compound resveratrol or stilbene have a higher specificity, efficacy and bioavailability, and lower toxicity. This paper is a review of the biological and pharmaceutical activities and the structure-activity relationships of resveratrol derivatives and analogs, providing a reference for the development of new drugs.%白藜芦醇因其抗氧化、抗肿瘤等生物活性,已成为全球医药界关注的焦点,但其靶点的低选择性、低效能以及体内低生物利用度是限制应用的主要难点.研究表明,以白藜芦醇或二苯乙烯为先导化合物得到的白藜芦醇衍生物或类似物具有较高的专一性、效能和生物利用度、较低的生物毒性.对白藜芦醇的主要衍生物和类似物的结构修饰与生物活性之间的关系进行了综述,希望能够为新型药物的研发提供参考.

  2. Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro

    Directory of Open Access Journals (Sweden)

    Wei Cheng

    2015-03-01

    Full Text Available Background/Aims: There is interest in drugs and rehabilitation methods to enhance neurogenesis and improve neurological function after brain injury or degeneration. Resveratrol may enhance hippocampal neurogenesis and improve hippocampal atrophy in chronic fatigue mice and prenatally stressed rats. However, its effect and mechanism of neurogenesis after stroke is less well understood. Sonic hedgehog (Shh signaling is crucial for neurogenesis in the embryonic and adult brain, but relatively little is known about the role of Shh signaling in resveratrol-enhanced neurogenesis after stroke. Methods: Neural stem cells (NSCs before oxygen-glucose deprivation/reoxygenation (OGD/R in vitro were pretreated with resveratrol with or without cyclopamine. Survival and proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical staining. The expressions and activity of signaling proteins and mRNAs were detected by immunocytochemistry, Western blotting, and RT-PCR analysis. Results: Resveratrol significantly increased NSCs survival and proliferation in a concentration-dependent manner after OGD/R injury in vitro. At the same time, the expression of Patched-1, Smoothened (Smo, and Gli-1 proteins and mRNAs was upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a Smo inhibitor. Conclusion: Shh signaling mediates resveratrol to increase NSCs proliferation after OGD/R injury in vitro.

  3. Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer

    Science.gov (United States)

    Prostate cancer is affected by lifestyle, particularly diet. Dietary polyphenols such as resveratrol possess anticancer properties and, therefore, chemopreventive and therapeutic potentials. Resveratrol has pleiotropic effect exerting its biological activity through multiple pathways and targets ass...

  4. Resveratrol enhances airway surface liquid depth in sinonasal epithelium by increasing cystic fibrosis transmembrane conductance regulator open probability.

    Directory of Open Access Journals (Sweden)

    Shaoyan Zhang

    Full Text Available BACKGROUND: Chronic rhinosinusitis engenders enormous morbidity in the general population, and is often refractory to medical intervention. Compounds that augment mucociliary clearance in airway epithelia represent a novel treatment strategy for diseases of mucus stasis. A dominant fluid and electrolyte secretory pathway in the nasal airways is governed by the cystic fibrosis transmembrane conductance regulator (CFTR. The objectives of the present study were to test resveratrol, a strong potentiator of CFTR channel open probability, in preparation for a clinical trial of mucociliary activators in human sinus disease. METHODS: Primary sinonasal epithelial cells, immortalized bronchoepithelial cells (wild type and F508del CFTR, and HEK293 cells expressing exogenous human CFTR were investigated by Ussing chamber as well as patch clamp technique under non-phosphorylating conditions. Effects on airway surface liquid depth were measured using confocal laser scanning microscopy. Impact on CFTR gene expression was measured by quantitative reverse transcriptase polymerase chain reaction. RESULTS: Resveratrol is a robust CFTR channel potentiator in numerous mammalian species. The compound also activated temperature corrected F508del CFTR and enhanced CFTR-dependent chloride secretion in human sinus epithelium ex vivo to an extent comparable to the recently approved CFTR potentiator, ivacaftor. Using inside out patches from apical membranes of murine cells, resveratrol stimulated an ~8 picosiemens chloride channel consistent with CFTR. This observation was confirmed in HEK293 cells expressing exogenous CFTR. Treatment of sinonasal epithelium resulted in a significant increase in airway surface liquid depth (in µm: 8.08+/-1.68 vs. 6.11+/-0.47,control,p<0.05. There was no increase CFTR mRNA. CONCLUSION: Resveratrol is a potent chloride secretagogue from the mucosal surface of sinonasal epithelium, and hydrates airway surface liquid by increasing CFTR

  5. Resveratrol-Enriched Rice Down-Regulates Melanin Synthesis in UVB-Induced Guinea Pigs Epidermal Skin Tissue.

    Science.gov (United States)

    Lee, Taek Hwan; Seo, Jae Ok; Do, Moon Ho; Ji, Eunhee; Baek, So-Hyeon; Kim, Sun Yeou

    2014-09-01

    Synthetic compounds that are used in the clinic to regulate skin hyperpigmentation, such as arbutin, hydroquinone, and kojic acid, are only moderately effective. But, their use is limited by side effects. As part of an effort to overcome the limitations, we developed resveratrol-enriched rice (RR) using genetic engineering technique. Each of resveratrol and rice has been reported to produce anti-melanogenic effects. Therefore, we hypothesized that RR would show more anti-melanogenic effects than those of resveratrol or rice alone. Anti-melanogenic effect of RR was done by using melan-a mouse melanocytes. The depigmenting efficacy was then observed following topical application of the RR to UVB-stimulated hyperpigmented dorsal skin of guinea pigs. Treatment with RR extract resulted a 21.4 ± 0.7% decrease in tyrosinase expression at melan-a cells. Colorimetric analysis showed a significantly lower depigmenting value by day 9 following treatment with RR in UVB-irradiated guinea pigs the dorsal skin (p<0.01), indicating that RR produced a depigmentation effect. By staining with Fontana-Masson stain, we found that the RR-treated group had more effect histopathologically in epidermal melanin production than resveratrol or rice alone-treated group. RR was associated with reduction in the levels of microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase and tyrosinase-related protein (TRP-2) expression, leading to inhibit epidermal melanin production by western blot analysis. This study suggests that the resveratrol-enriched rice may be a promising candidate in regulating skin pigmentation with UVB exposure. PMID:25414774

  6. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes

    Directory of Open Access Journals (Sweden)

    Orlando Robert A

    2008-06-01

    NF-κB activation and resulted in a reduction of TNF-α, IL-1β, IL-6, and COX-2 gene expression (IC50 = 2 μM and a reduction of secreted IL-6 and PGE2 (IC50 ~ 20 μM. Conclusion Curcumin and resveratrol are able to inhibit TNFα-activated NF-κB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.

  7. Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

    Directory of Open Access Journals (Sweden)

    Lozano-Pérez AA

    2014-09-01

    fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects. Keywords: immunomodulatory, cytokines, TNBS rat colitis, RAW 264.7 macrophage cells, antioxidant

  8. High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes

    OpenAIRE

    Lee, Haemi; Kim, Jae-Woo

    2013-01-01

    Background Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes. Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to obs...

  9. Inhibition of sphingolipid metabolism enhances resveratrol chemotherapy in human gastric cancer cells.

    Science.gov (United States)

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-09-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 μM) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells. PMID:24009836

  10. Resveratrol supplementation does not improve metabolic function in non-obese women with normal glucose tolerance

    OpenAIRE

    Yoshino, Jun; Conte, Caterina; Fontana, Luigi; Mittendorfer, Bettina; Imai, Shin-ichiro; Kenneth B Schechtman; Gu, Charles; Kunz, Iris; Fanelli, Filippo Rossi; Patterson, Bruce W.; Klein, Samuel

    2012-01-01

    Resveratrol has been reported to improve metabolic function in metabolically-abnormal rodents and humans, but has not been studied in non-obese people with normal glucose tolerance. We conducted a randomized, double-blind, placebo-controlled trial to evaluate the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in non-obese, postmenopausal women with normal glucose tolerance. Although resveratrol supplementation increased plasma resveratrol concentration, it did not ch...

  11. Resveratrol modifies tephritid fruit fly response to nutritional and radiation stress

    Science.gov (United States)

    Resveratrol is a recently discovered compound. Three concentrations (50, 100, 200 µM) of resveratrol were evaluated against Bactrocera dorsalis and B. cucurbitae by incorporating resveratrol into fruit fly liquid larval diet under the following conditions: 1) with or without wheat germ oil (WGO) in ...

  12. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects

    DEFF Research Database (Denmark)

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás;

    2015-01-01

    model to study the possibility of recovering from HGPS bone disease upon silencing of the HGPS mutation, and the potential benefits from treatment with resveratrol. We show that complete silencing of the transgenic expression of progerin normalized bone morphology and mineralization already after 7...... weeks. The improvements included lower frequencies of rib fractures and callus formation, an increased number of osteocytes in remodeled bone, and normalized dentinogenesis. The beneficial effects from resveratrol treatment were less significant and to a large extent similar to mice treated with sucrose...... alone. However, the reversal of the dental phenotype of overgrown and laterally displaced lower incisors in HGPS mice could be attributed to resveratrol. Our results indicate that the HGPS bone defects were reversible upon suppressed transgenic expression and suggest that treatments targeting aberrant...

  13. Autophagy involved in resveratrol increased radiosensitivity in glioma stem cells

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of Resveratrol combined with X-ray on radiosensitivity in glioma stem cells. Methods: The proliferation inhibition of glioma stem cells induced by X-rays and Resveratrol was assessed with MTT assay. The activation of proapoptotic effect was characterized by Hoechst 33258 stain. MDC stain and Western blot analysis were used to analyze the autophagy mechanism in X-rays-induced death of glioma stem cells. Results: MTT assay indicated that X-rays and Resveratrol decreased the viability of glioma stem cells (P<0.05); we found the proliferative inhibition of glioma stem cells was declined when we used 3-MA to inhibit autophagy(P<0.05). When the cells were treated by the Resveratrol and x-rays, their spherical shape were changed. Apoptosis was induced in glioma stem cells by combined X-rays and Resveratrol as detected by Hoechst 33258 staining. In addition, autophagy was induced in glioma stem cells in the combined treatment group as detected by MDC staining. Western blotting showed that Bcl-2 expression was decreased. in the combined treatment group (P<0.01), and the LC3-Ⅱ expression was increased in the combined treatment group (P<0.01). Conclusion: Resveratrol can increased the radiation sensitivity of glioma stem cells, the apoptosis and autophagy was induced in the glioma stem cells in the combined treatment X-rays and Resveratrol. Our results suggest that autophagy plays an essential role in the regulation of radiosensitization of glioma stem cells. (authors)

  14. Angiomodulatory properties of Rhodiola spp. and other natural antioxidants.

    Science.gov (United States)

    Radomska-Leśniewska, Dorota M; Skopiński, Piotr; Bałan, Barbara J; Białoszewska, Agata; Jóźwiak, Jarosław; Rokicki, Dariusz; Skopińska-Różewska, Ewa; Borecka, Anna; Hevelke, Agata

    2015-01-01

    Disturbances of angiogenesis and oxidative stress can lead to many serious diseases such as cancer, diabetes or ischemic heart disease. Substances neutralizing oxidative stress are known as antioxidants. They can affect angiogenesis process also, and thus, they modulate therapy results. Antioxidants become more and more frequently used in order to maintain homeostasis of the organism and diminish the risk of disease. Herein, we introduce some antioxidant preparations of natural plant origin (Rhodiola, Aloe vera, Resveratrol, Echinacea, Plumbagin) and antioxidant supplements (Padma 28, Reumaherb, Resvega). Analyses of their angiogenic properties, their multidirectional molecular effect on angiogenesis as well as medical application are within the scope of this review. Most of presented preparations down regulate neovascularization. They can be safely administered to patients with abnormally high angiogenesis. Rhodiola modulates, and Echinacea, Aloe vera and Plumbagin inhibit tumour-related angiogenesis in vitro and in vivo (animal models). Resveratrol and Resvega reduce neovascularization in the eye and may be applicable in eye disorders. Padma 28 preparation exhibits angioregulatory activity, decreasing high angiogenesis of cancer cells and increasing physiological angiogenesis, therefore can be used in therapy of patients with various disturbances of angiogenesis. Antioxidant application in the case of angiogenesis-related diseases should take into consideration angiogenic status of the patient. PMID:26557041

  15. Resveratrol attenuates the Na(+-dependent intracellular Ca(2+ overload by inhibiting H(2O(2-induced increase in late sodium current in ventricular myocytes.

    Directory of Open Access Journals (Sweden)

    Chunping Qian

    Full Text Available BACKGROUND/AIMS: Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H(2O(2-induced increase in late sodium current (I(Na.L which augmented the reverse Na(+-Ca(2+ exchanger current (I(NCX, and the diastolic intracellular Ca(2+ concentration in ventricular myocytes. METHODS: I(Na.L, I(NCX, L-type Ca(2+ current (I(Ca.L and intracellular Ca(2+ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix, respectively, in rabbit ventricular myocytes. RESULTS: Resveratrol (10, 20, 40 and 80 µM decreased I(Na.L in myocytes both in the absence and presence of H(2O(2 (300 µM in a concentration dependent manner. Ranolazine (3-9 µM and tetrodotoxin (TTX, 4 µM, I(Na.L inhibitors, decreased I(Na.L in cardiomyocytes in the presence of 300 µM H(2O(2. H(2O(2 (300 µM increased the reverse I(NCX and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H(2O(2 of the diastolic intracellular Ca(2+ fura-2 fluorescence intensity (FFI, fura-fluorescence intensity change (△FFI, maximal velocity of intracellular Ca(2+ transient rise and decay. As expected, 2 µM TTX had no effect on I(Ca.L. CONCLUSION: Resveratrol protects the cardiomyocytes by inhibiting the H(2O(2-induced augmentation of I(Na.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias.

  16. A randomized, controlled trial of the effects of resveratrol administration in performance horses with lameness localized to the distal tarsal joints.

    Science.gov (United States)

    Watts, Ashlee E; Dabareiner, Robin; Marsh, Chad; Carter, G Kent; Cummings, Kevin J

    2016-09-15

    OBJECTIVE To determine the effect of resveratrol administration in performance horses with lameness localized to the distal tarsal joints. DESIGN Randomized, blinded, placebo-controlled clinical trial. ANIMALS 45 client-owned horses with lameness localized to the distal tarsal joints. PROCEDURES All horses received injections of triamcinolone acetonide in the centrodistal and tarsometatarsal joints of both hind limbs. A placebo or a supplement containing resveratrol was fed twice daily by owners for 4 months. Primary outcomes were horse performance as determined by rider opinion (better, worse, or the same) and change in lameness severity from the enrollment examination. RESULTS Complete data were obtained for 21 horses that received resveratrol and 20 that received the placebo. Percentage of riders who reported that the horse's performance was better, compared with worse or the same, was significantly higher for the resveratrol group than for the placebo group after 2 (20/21 [95%] vs 14/20 [70%]) and 4 (18/21 [86%] vs 10/20 [50%]) months. The change in A1:A2 ratio between the enrollment and 4-month recheck examinations was significantly better for horses in the resveratrol versus placebo group. However, subjective lameness scores and degree of asymmetry of pelvis movement did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in performance horses with lameness localized to the distal tarsal joints, injection of triamcinolone in the centrodistal and tarsometatarsal joints of both hind limbs followed by oral supplementation with resveratrol for 4 months resulted in reduced lameness, compared with triamcinolone injection and supplementation with a placebo. PMID:27585103

  17. Dual regulatory effects of resveratrol on activation of NF-κB and cell proliferation in human embryonal kidney 293 cells

    Institute of Scientific and Technical Information of China (English)

    YIN Hong; CHENG Guifang

    2005-01-01

    Resveratrol (3,4′,5-trihydroxystilbene, Res), a naturally occurring polyphenol, exhibits antioxidant, anti- inflammatory, potential chemopreventive and chemotherapeutic properties in preclinical studies. To further understand its potential clinical efficacy and safety, effect of Res at 10-9―10-4 mol/L on human embryonal kidney (HEK293) cell proliferation and its potential mechanism were investigated in present study. Cell viability was detected by using trypan blue dye exclusion method. Cell cycle and apoptosis were analyzed by flow cytometry with propidium iodide stain. Activation of nuclear factor-κB (NF-κB) was determined by luciferase reporter gene assay using stably transfected HEK293/κB-luc cells. Secretion of human interleukin-8 (hIL-8) was measured by ELISA. Our results show that HEK293 cell proliferation was significantly stimulated by 10-7 mol/L Res after treatment for 48 hours, or by 10-8―10-7 mol/L Res combinated with 10 ng/mL TNFα for 24 h, but was suppressed by 10-4 mol/L Res with or without TNFα. Both endogenous and TNFα-induced NF-κB activation were downregulated by Res at 10-7 mol/L, but were upregulated at 10-4 mol/L. With 10-4 mol/L Res, the content of secreted IL-8 was increased, and apoptosis rate was increased from less than 5% to 10%, together with significant cell-cycle arrest in S phase. TNFα has coordinative effects with Res on HEK293 cell apoptosis, cell-cycle arrest and IL-8 secretion. These results indicate that Res promotes cell proliferation at low concentration through down-regulation of NF-κB activation in HEK293, but suppresses its growth at high concentration through up-regulation of NF-κB activation, increasing IL-8 and cell-cycle arrest. As resveratrol has dual regulatory effect on cell proliferation in vitro, comprehensive evaluation of its potential clinical utility is needed.

  18. Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang, E-mail: molpharm@163.com; Sun, Yang, E-mail: yangsun@nju.edu.cn

    2013-03-01

    In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

  19. Resveratrol induces apoptosis in human esophageal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Yun Yan; Ya-Ni Sun; Ju-Ren Zhu

    2003-01-01

    AIM: To investigate the apoptosis in esophageal cancer cells induced by resveratrol, and the relation between this apoptosis and expression of Bcl-2 and Bax.METHODS: In in vitro experiments, MTr assay was used to determine the cell growth inhibitory rate. Transmission electron microscope and TUNEL staining method were used to quantitatively and qualitively detect the apoptosis status of esophageal cancer cell line EC-9706 before and after the resveratrol treatment. Immunohistochemical staining was used to detect the expression of apoptosis-regulated gene Bcl-2 and Bax.RESULTS: Resveratrol inhibited the growth of esophageal cancer cell line EC-9706 in a dose-and time-dependent manner. Resveratrol induced EC-9706 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation and apoptotic body formation. TUNEL assay showed that after the for 24 to 96 hours, the AIs were apparently increased with treated time (P<0.05). Immunohistochemical staining showed that after the treatment of EC-9706 cells with proteins were apparently reduced with treated time (P<0.05)and the PRs of Bax proteins were apparently increased with treated time (P<0.05).CONCLUSION: Resveratrol is able to induce the apoptosisin esophageal cancer. This apoptosis may be mediated by down-regulating the apoptosis-regulated gene Bcl-2 and upregulating the expression of apoptosis-regulated gene bax.

  20. Anti-hepatoma activity of resveratrol in vitro

    Institute of Scientific and Technical Information of China (English)

    Zhong-Jie Sun; Cheng-En Pan; Hong-Shan Liu; Guo-Jun Wang

    2002-01-01

    AIM: To study the anti-tumor effect of resveratrol alone andthe synergistic effects of resveratrol with 5-FU on the growthof H22 calls line in vitro.METHODS: The number of cells was measured by MTTmethod, the morphological changes of H22 cells wereinvestigated under microscopy and electron microscopy.RESULTS: Resveratrol inhibited the growth of hepatomacells line H22 in a dose- and time-dependent manner. IC50 ofthe resverstrol on Hl22 cells was 6.57mg@ L- 1. The synergisticanti-tumor effects of resveratrol with 5-FU increased to agreater extent than for Hl22 cells treated with 5-FU alone(70.2% vs 28.4%) (P < 0.05). Under microscope andelectron microscope, characteristics of apoptosis such astypical apoptotic bodies were commonly found in tumorcells in the drug-treated groups.CONCLUSION: Resveratrol can suppresses the growth of H22cells in vitro, its anti-tumor activity may occur through theinduction of apoptosis.

  1. Antioxidants of Edible Mushrooms

    Directory of Open Access Journals (Sweden)

    Maja Kozarski

    2015-10-01

    Full Text Available Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality.

  2. Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells

    Science.gov (United States)

    Barbosa, João P; Neves, Ana R; Silva, Andreia M; Barbosa, Mário A; Reis, M Salette; Santos, Susana G

    2016-01-01

    Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation.

  3. Resveratrol primes the effects of physical activity in old mice.

    Science.gov (United States)

    Rodríguez-Bies, Elizabeth; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

    2016-09-01

    Decrease in muscle mass and performance with ageing is one of the main factors of frailty in the elderly. Maintenance of muscle performance by involving in physical activities is essential to increase independence and quality of life among elderly. The use of natural compounds with ergogenic activity in old people would increase the effect of moderate exercises in the maintenance of physiological muscle capacity. Resveratrol (RSV), a polyphenol found in walnuts, berries and grapes, shows this ergogenic activity. By using young, mature and old mice as models, we have found that RSV improves muscle performance in mature and old animals but not in young animals. Without showing significant effect by itself, RSV primed the effect of exercise by increasing endurance, coordination and strength in old animals. This effect was accompanied by a higher protection against oxidative damage and an increase in mitochondrial mass. RSV increased catalase and superoxide dismutase protein levels in muscle and primed exercise to reverse the decrease in their activities during ageing. Furthermore, RSV increased the level of mitochondrial mass markers such as cytochrome C, mitochondrial transcription factor A and nuclear respiratory factor-1 in muscle in exercised animals. Our results indicate that RSV can be considered an ergogenic compound that helps maintain muscle performance during ageing and subsequently reduces frailty and increases muscle performance in old individuals practising moderate exercise. PMID:27488121

  4. Phenolic composition, physicochemical properties and antioxidant activity of interspecific hybrids of grapes growing in Poland.

    Science.gov (United States)

    Samoticha, Justyna; Wojdyło, Aneta; Golis, Tomasz

    2017-01-15

    The study evaluated fruit quality parameters and chemical properties (soluble solids, pH, total acidity and total sugars content, phenolic compounds and antioxidant activity (ABTS, FRAP and ORAC methods)) of 30 grape cultivars of white, red and pink grape, as 28 interspecific hybrids and 2 Vitis vinifera L. popularly grown in Poland. Some of them were analyzed for the first time. A total of 49 polyphenolic compounds were identified by LC-PDA-QTOF/MS and quantified by UPLC-PDA-FL, as 26 anthocyanins, 9 flavonols and flavons, 7 phenolic acids, 6 flavan-3-ols, and 1 stilbene. The content of total polyphenols ranged from 1037.0 (Cascade cv.) to 5759.1mg/100gdm (Roesler cv.). However, the content of stilbene represented by trans resveratrol-3-glucoside was only 18.5-70.5mg/100gdm. Red grape cultivars like Roesler, Rothay and Swenson Red were characterized by the highest content of bioactive compounds and antioxidant activity (significantly more than 24, 12 and 53mmol TE/100gdm, by ABTS, FRAP and ORAC, respectively). Average total acidity and soluble solids for white (0.95g of tartaric acid in 100gfm and 17.1°Bx, respectively) and for red and pink (0.93g of tartaric acid in 100gfm and 17.4°Bx, respectively) cultivars were not significantly different (p>0.05). PMID:27542475

  5. What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

    DEFF Research Database (Denmark)

    Vang, Ole; Ahmad, Nihal; Baile, Clifton A.;

    2011-01-01

    Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of...... resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was...... used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed ‘‘side effects’’ caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an...

  6. Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation

    OpenAIRE

    Lee, Yoon-Jin; Im, Jae-Hyuk; Lee, David M; PARK, Ji-Sung; Won, Seong Youn; Cho, Moon-Kyun; Nam, Hae-Seon; Lee, Yong-Jin; LEE, SANG-HAN

    2012-01-01

    We previously reported that MSTO-211H cells have a higher capacity to regulate Nrf2 activation in response to changes in the cellular redox environment. To further characterize its biological significance, the response of Nrf2, a transcription factor that regulates ARE-containing genes, on the synergistic cytotoxic effect of clofarabine and resveratrol was investigated in mesothelioma cells. The combination treatment showed a marked growth-inhibitory effect, which was accompanied by suppressi...

  7. Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation

    OpenAIRE

    Yoon-Jin Lee1,2, Jae-Hyuk Im3, David M. Lee4, Ji-Sung Park3, Seong Youn Won2, Moon-Kyun Cho2, Hae-Seon Nam2, Yong-Jin Lee1 & Sang-Han Lee1,3,*

    2012-01-01

    We previously reported that MSTO-211H cells have a highercapacity to regulate Nrf2 activation in response to changes inthe cellular redox environment. To further characterize itsbiological significance, the response of Nrf2, a transcriptionfactor that regulates ARE-containing genes, on the synergisticcytotoxic effect of clofarabine and resveratrol was investigatedin mesothelioma cells. The combination treatment showed amarked growth-inhibitory effect, which was accompanied bysuppression of Nr...

  8. Copper and resveratrol attenuates serum catalase, glutathione peroxidase, and element values in rats with DMBA-induced mammary carcinogenesis.

    Science.gov (United States)

    Skrajnowska, Dorota; Bobrowska-Korczak, Barbara; Tokarz, Andrzej; Bialek, Slawomir; Jezierska, Ewelina; Makowska, Justyna

    2013-12-01

    In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4·5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p copper plus resveratrol (p cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research.

  9. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    Directory of Open Access Journals (Sweden)

    Nádia Rezende Barbosa Raposo

    2012-10-01

    Full Text Available Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL, two times more active than resveratrol (IC50 = 57.05 µg/mL, followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

  10. Photoionization access to cyclodextrin-encapsulated resveratrol phenoxy radicals and their repair by ascorbate across the phase boundary.

    Science.gov (United States)

    Kerzig, Christoph; Goez, Martin

    2016-07-27

    Repair reactions of phenoxy radicals by co-antioxidants are key parts of radical scavenging cascades in nature. Yet, kinetic and mechanistic studies of such repairs are scarce, particularly at biologically relevant interfaces. For the popular red-wine polyphenol resveratrol, we present the first example of repairing a cyclodextrin-complexed phenoxy radical by a water soluble co-antioxidant (ascorbate), a reaction of practical importance given the fact that both antioxidants and cyclodextrins are large-scale food additives. To prepare the phenoxy radical from its parent compound inside the cavities of native or hydroxypropyl-substituted α- and β-cyclodextrins, we employed laser photoionization with UV-A (355 nm), which does not rely on additional reagents, and therefore leaves the repair completely undisturbed. A global fit of the intensity dependence pinpoints the cyclodextrin influences on the biphotonic resveratrol ionization as a shift of the ground-state absorption spectrum and a longer life of the first excited state due to the suppression of the geometrical isomerization by the rigid containers, whereas the actual electron ejection from an upper excited state is almost medium-independent. The exchange of the phenoxy radical between the cyclodextrin interior and the aqueous bulk is immeasurably slow on the timescale of its repair by the ascorbate monoanion. Kinetic H/D isotope effects and activation entropies identify the repair at the cyclodextrin-water interface as a concerted proton-electron transfer with no mechanistic difference to homogeneous aqueous solution. The activation enthalpies reveal a steric repulsion between ascorbate and cyclodextrin that indicates a deeper embedding of the less hydrophilic phenoxy radical in the macrocycle compared to the parent compound, with the observed structure-rate relationships explainable on the basis of the cavity diameter and depth. PMID:27418479

  11. Bioactive form of resveratrol in glioblastoma cells and its safety for normal brain cells

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Shu

    2013-05-01

    Full Text Available ABSTRACTBackground: Resveratrol, a plant polyphenol existing in grapes and many other natural foods, possesses a wide range of biological activities including cancer prevention. It has been recognized that resveratrol is intracellularly biotransformed to different metabolites, but no direct evidence has been available to ascertain its bioactive form because of the difficulty to maintain resveratrol unmetabolized in vivo or in vitro. It would be therefore worthwhile to elucidate the potential therapeutic implications of resveratrol metabolism using a reliable resveratrol-sensitive cancer cells.Objective: To identify the real biological form of trans-resveratrol and to evaluate the safety of the effective anticancer dose of resveratrol for the normal brain cells.Methods: The samples were prepared from the condition media and cell lysates of human glioblastoma U251 cells, and were purified by solid phase extraction (SPE. The samples were subjected to high performance liquid chromatography (HPLC and liquid chromatography/tandem mass spectrometry (LC/MS analysis. According to the metabolite(s, trans-resveratrol was biotransformed in vitro by the method described elsewhere, and the resulting solution was used to treat U251 cells. Meanwhile, the responses of U251 and primarily cultured rat normal brain cells (glial cells and neurons to 100μM trans-resveratrol were evaluated by multiple experimental methods.Results: The results revealed that resveratrol monosulfate was the major metabolite in U251 cells. About half fraction of resveratrol monosulfate was prepared in vitro and this trans-resveratrol and resveratrol monosulfate mixture showed little inhibitory effect on U251 cells. It is also found that rat primary brain cells (PBCs not only resist 100μM but also tolerate as high as 200μM resveratrol treatment.Conclusions: Our study thus demonstrated that trans-resveratrol was the bioactive form in glioblastoma cells and, therefore, the biotransforming

  12. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor

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    Qureshi Asaf A

    2012-07-01

    Full Text Available Abstract Background Altered immune function during ageing results in increased production of nitric oxide (NO and other inflammatory mediators. Recently, we have reported that NO production was inhibited by naturally-occurring proteasome inhibitors (quercetin, δ-tocotrienol, and riboflavin in lipopolysaccharide (LPS-stimulated RAW264.7 cells, and thioglycolate-elicited peritoneal macrophages from C57BL/6 mice. In a continuous effort to find more potent, non-toxic, commercially available, naturally-occurring proteasome inhibitors that suppress inflammation, the present study was carried out to describe the inhibition of NF-κB activation and NO, TNF-α, IL-6, IL-1β, and iNOS expression by trans-resveratrol, trans-pterostilbene, morin hydrate, and nicotinic acid in LPS-induced RAW 264.7 cells and thioglycolate-elicited peritoneal macrophages from C57BL/6 and BALB/c mice. Results The present results indicate that resveratrol, pterostilbene, and morin hydrate caused significant inhibition (>70% to 90%; P 40%; P 60%; P 40%; P P  Conclusions The present results clearly demonstrate that resveratrol and pterostilbene are particularly potent proteasome inhibitors that suppress expression of genes, and production of inflammatory products in LPS-stimulated RAW 264.7 cells, and macrophages from C57BL/6 and BALB/c mice. Resveratrol and pterostilbene which are present in grapes, blueberries, and red wine, have been implicated as contributing factors to the lower incidence of cardiovascular disease in the French population, despite their relatively high dietary fat intake. Consequently, it appears likely that the beneficial nutritional effects of resveratrol and pterostilbene are due at least in part, to their ability to inhibit NF-κB activation by the proteasome, thereby suppressing activation of pro-inflammatory cytokines and iNOS genes, resulting in decreased secretion of TNF-α, IL-1β, IL-6, and NO levels, in response to inflammatory stimuli

  13. Protective effect of Resveratrol on myocardial injury in diabetic rats%白藜芦醇对2型糖尿病大鼠心肌病变的保护作用

    Institute of Scientific and Technical Information of China (English)

    董洪亮

    2013-01-01

    目的 探讨白藜芦醇(Res)对糖尿病心肌病大鼠心肌损伤的保护作用及机制.方法 采用链脲佐菌素(STZ)诱导2型糖尿病大鼠模型,给予不同剂量Res(10,20,40 mg/(kg· d))治疗6周后,检测各组大鼠空腹血糖、心脏质量指数、左心室质量指数、血清及心肌超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量;Masson染色观察胶原表达变化及测量心肌胶原容积百分数;比较各组大鼠心肌中总抗氧化能力(T-AOC)及过氧化氢(H2 O2)的含量,Western bolt检测心肌组织中p22phox蛋白表达.结果 与正常组相比,模型组大鼠空腹血糖、心脏质量指数及左心室质量指数明显增高,心肌胶原容积分数明显升高,血清及心肌SOD活力及心肌T-AOC明显降低,心肌组织p22phox蛋白表达及H2O2和MDA含量显著升高(P均<0.01).与糖尿病组相比,Res各剂量组灌胃6周后上述指标均得到明显改善(P <0.05或0.01).结论 Res可下调2型糖尿病大鼠心肌p22phox蛋白过度表达,减轻氧化应激对心肌的损害,发挥心肌保护作用.%Objective It is to investigate the protective effects and mechanism of Resveratrol on myocardial injury in diabetic rats. Methods Streptozotocin-induced diabetic rats were given Resveratrol (10, 20, 40 mg/kg/d) for 6 weeks. The changes in blood glucose (BG) , cardiac mass index and left ventricular mass index were calculated, and serum and myocardium superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Morphological change was observed by Mas-son staining and myocardial collagen volume fraction (CVF) was measured by image analyzer. The total antioxidant capacity ( T- AOC) and hydrogen peroxide ( H2O2) in myocardial tissue were compared. In addition, the expressions of p22phox protein in myocardium were determined by western bolt. Results Compared with the normal control group, the BC, cardiac mass index, left ventricular mass index and CVF values were significantly increased. The

  14. Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation

    Directory of Open Access Journals (Sweden)

    Yoon-Jin Lee1,2, Jae-Hyuk Im3, David M. Lee4, Ji-Sung Park3, Seong Youn Won2, Moon-Kyun Cho2, Hae-Seon Nam2, Yong-Jin Lee1 & Sang-Han Lee1,3,*

    2012-11-01

    Full Text Available We previously reported that MSTO-211H cells have a highercapacity to regulate Nrf2 activation in response to changes inthe cellular redox environment. To further characterize itsbiological significance, the response of Nrf2, a transcriptionfactor that regulates ARE-containing genes, on the synergisticcytotoxic effect of clofarabine and resveratrol was investigatedin mesothelioma cells. The combination treatment showed amarked growth-inhibitory effect, which was accompanied bysuppression of Nrf2 activation and decreased expression ofheme oxygenase-1 (HO-1. While transient overexpression ofNrf2 conferred protection against the cytotoxicity caused bytheir combination, knockdown of Nrf2 expression using siRNAenhanced their cytotoxic effect. Pretreatment with Ly294002, aPI3K inhibitor, augmented the decrease in HO-1 level by theircombination, whereas no obvious changes were observed inNrf2 levels. Altogether, these results suggest that the synergisticcytotoxic effect of clofarabine and resveratrol was mediated, atleast in part, through suppression of Nrf2 signaling.

  15. Plant derived antioxidants and antifibrotic drugs:past, present and future

    Institute of Scientific and Technical Information of China (English)

    Devaraj Ezhilarasan; Etienne Sokal; Sivanesan Karthikeyan; Mustapha Najimi

    2014-01-01

    Hepatic fibrosis occurs as a wound-healing process after several forms of chronic hepatic injury. Activation and proliferation of hepatic stellate cells play pivotal role in the pathogenesis of hepatic fibrosis. Many researchers, from the therapeutic perspective, have focused their attention on searching for novel agents with inhibitory effects on hepatic stellate cells proliferation and activation to prevent hepatic fibrogenesis and a number of plant derived antioxidants have been tested as anti-fibrogenic agents, they generally suppress proliferation and collagen synthesis. Plants remain an imperative source of novel drugs, novel drug leads and new chemical entities. The plant based drug discovery resulted primarily in the development of antioxidant, anti-cancer and other anti-infectious agents and continues to contribute to the new leads in clinical trials. This review summarizes some of those most important plant derived anti-fibrotic drugs and their beneficial effects on experimentally induced hepatic fibrosis in vitro and in vivo. The plant derived antioxidant compounds described herein are curcumin, silymarin, silibinin, baicalein, resveratrol, salvianolic acids, tetrandine, quercetin and berberine. Studies from ours and as demonstrated by pervious workers much information has been accumulated over the past two decades through in vivo and in vitro. In light of those studies, it has been confirmed that plants derived antioxidants, particularly flavanoids, show a significant influence to block hepatic fibrosis regardless of any etiology. This review outlines recent progress in the use of plant derived drugs against experimentally induced liver fibrosis by in vitro and in vivo studies and summarizes the possible mechanisms anti-fibrotic effects of these compounds.

  16. Nutraceutical Antioxidants as Novel Neuroprotective Agents

    Directory of Open Access Journals (Sweden)

    Daniel A. Linseman

    2010-11-01

    Full Text Available A variety of antioxidant compounds derived from natural products (nutraceuticals have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1 flavonoid polyphenols like epigallocatechin 3-gallate (EGCG from green tea and quercetin from apples; (2 non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3 phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4 organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2 transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.

  17. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

    Science.gov (United States)

    Kapadia, Govind J; Azuine, Magnus A; Tokuda, Harukuni; Takasaki, Midori; Mukainaka, Teruo; Konoshima, Takao; Nishino, Hoyoku

    2002-06-01

    skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.

  18. A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model.

    Science.gov (United States)

    Ozcan Cenksoy, Pinar; Oktem, Mesut; Erdem, Ozlem; Karakaya, Cengiz; Cenksoy, Cahit; Erdem, Ahmet; Guner, Haldun; Karabacak, Onur

    2015-03-01

    The aim of our study was to evaluate the effectiveness of resveratrol in experimentally induced endometrial implants in rats through inhibiting angiogenesis and inflammation. Endometrial implants were surgically induced in 24 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were divided into resveratrol (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups and medicated for 21 d. In the third surgery, the measurements of mean areas and histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements in blood and peritoneal fluid samples, and immunohistochemical staining were evaluated. After treatment, significant reductions in mean areas of implants (p treatment were also significantly lower in the resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting angiogenesis and inflammation. Further studies are needed to determine the optimum effective dose in humans and to evaluate other effects on reproductive physiology.

  19. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

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    Xiaoli Chang

    Full Text Available Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR, while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5 transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death.

  20. Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release

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    Feng Zhang

    2012-01-01

    Full Text Available Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson’s disease (PD. Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia cultures were applied to investigate the neurotrophic effects mediated by resveratrol on dopamine (DA neurons and further explore the role of neurotrophic factors in its actions. Results showed resveratrol produced neurotrophic effects on cultured DA neurons. Additionally, astroglia-derived neurotrophic factors release was responsible for resveratrol-mediated neurotrophic properties as evidenced by the following observations: (1 resveratrol failed to exert neurotrophic effects on DA neurons in the cultures without astroglia; (2 the astroglia-conditioned medium prepared from astroglia-enriched cultures treated with resveratrol produced neurotrophic effects in neuron-enriched cultures; (3 resveratrol increased neurotrophic factors release in the concentration- and time-dependent manners; (4 resveratrol-mediated neurotrophic effects were suppressed by blocking the action of the neurotrophic factors. Together, resveratrol could produce neurotrophic effects on DA neurons through prompting neurotrophic factors release, and these effects might open new alternative avenues for neurotrophic factor-based therapy targeting PD.

  1. Development and validation of an RP-HPLC method for quantification of trans-resveratrol in the plant extracts

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    Cvetković Žika S.

    2015-01-01

    Full Text Available New, simple, cost effective, accurate and reproducible RP-HPLC method was developed and validated for the quantification of trans-resveratrol in the extracts of grape exocarp and seeds. The method has proved to be simpler and faster than available methods. Methanol was used as a mobile phase with a flow rate of 1.0 cm3 min-1, while the quantification was effected at 306 nm. The separation was performed at 35°C using a C18 column. The results showed that the peak area response was linear in the concentration range of 1-40 μg cm-3. The values of LOD and LOQ were found to be 0.125 and 0.413 μg cm-3, respectively. The antioxidant activity of the extracts was determined using DPPH assay. The ability of DPPH radicals inhibition decreases in the following order: the extract of grape exocarp > trans-resveratrol standard > the extract of grape seeds. [Projekat Ministarstva nauke Republike Srbije, br. TRp-34012

  2. Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol.

    Science.gov (United States)

    Xia, Ning; Strand, Susanne; Schlufter, Frank; Siuda, Daniel; Reifenberg, Gisela; Kleinert, Hartmut; Förstermann, Ulrich; Li, Huige

    2013-08-01

    Many of the cardiovascular protective effects of resveratrol are attributable to an enhanced production of nitric oxide (NO) by the endothelial NO synthase (eNOS). Resveratrol has been shown to enhance eNOS gene expression as well as eNOS enzymatic activity. The aim of the present study was to analyze the molecular mechanisms of eNOS transcriptional activation by resveratrol. Treatment of human EA.hy 926 endothelial cells with resveratrol led to a concentration-dependent upregulation of eNOS expression. In luciferase reporter gene assay, resveratrol enhanced the activity of human eNOS promoter fragments (3500, 1600, 633 and 263bp in length, respectively), indicating that the proximal promoter region is required for resveratrol-induced eNOS transcriptional activation. Knockdown of the NAD(+)-dependent protein deacetylase sirtuin 1 (SIRT1) by siRNA prevented the upregulation of eNOS mRNA and protein by resveratrol. Forkhead box O (FOXO) transcription factors are established downstream targets of SIRT1. siRNA-mediated knockdown of FOXO1 and FOXO3a abolished the effect of resveratrol on eNOS expression, indicating the involvement of these factors. Resveratrol treatment enhanced the expression of FOXO1 and FOXO3a in EA.hy 926 cells. Reporter gene assay using promoter containing forkhead response elements showed increased FOXO factor activity by resveratrol. In electrophoretic mobility shift assay, the enhanced binding of nuclear proteins to the eNOS promoter regions by resveratrol could be blocked by antibodies against FOXO1 and FOXO3a. In conclusion, resveratrol enhances the expression and activity of FOXO transcription factors. The SIRT1/FOXO factor axis is involved in resveratrol-induced eNOS transcriptional activation.

  3. Challenges in Analyzing the Biological Effects of Resveratrol

    DEFF Research Database (Denmark)

    Erdogan, Cihan Süleyman; Vang, Ole

    2016-01-01

    The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of...

  4. Effects of Resveratrol on Inflammatory Bowel Disease: A Review

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    Mee Young Hong

    2014-06-01

    Full Text Available Inflammatory bowel disease (IBD is an autoimmunedisease characterized by chronic inflammation in the colon and small intestine. IBD produces many symptoms that can cause discomfort and a modified lifestyle. IBD has no cure, only drugs used to suppress its inflammation, which have exhibited harmful side effects. Resveratrol, 3,5,40 -trihydroxy-trans-stilbene, is a natural phenol with anti-inflammatory attributes. Studies have found consistent results showing that resveratrol supplementation in experimental rodent models of IBD can reduce inflammatory biomarkers. This review presents experimental animal models of IBD showing that resveratrol supplementation can down-regulate inflammatory pathways of MAPK and NF-κb, lessen COX-2, modify cytokines, diminish leukocytes, alter intestinal microflora, and decrease clinical symptoms in vivo, all of which contribute to an improved state of the disease. These outcomes, however, have not yet been studiedin naturally occurring IBD in humans. Future research should attempt and refine to determine if resveratrol could be an effective therapy for IBD in humans.

  5. Resveratrol Photoisomerization: An Integrative Guided-Inquiry Experiment

    Science.gov (United States)

    Bernanrd, Elyse; Britz-McKibbin, Philip; Gernigon, Nicholas

    2007-01-01

    The recently introduced integrative guided-inquiry experiment explains various fundamental chemical concepts related to different biologically relevant molecules like resveratrol. The results of the photoisomerization of the molecule show that it is a very effective chemopreventative agent that can extend the lifespan in several organisms.

  6. Resveratrol Tetramers from the Roots ofAmpelopsis sinica

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new resveratrol tetramer, sinicin A was isolated from the roots ofAmpelopsis sinica,with four known tetramers: vitisin A, cis-vitisin B, ampelopsin H and hopeaphenol. The structure and stereochemistry of sinicin A have been established on the basis of 1D and 2D NMR spectroscopic techniques.

  7. Resveratrol tetramer of hopeaphenol isolated from Shorea johorensis (Dipterocarpaceae)

    Science.gov (United States)

    Aisha, Farra; Din, Laily B.; Yaacob, W. A.

    2014-09-01

    Hopeaphenol (1) as a resveratrol tetramer was isolated from the bark of Shorea johorensis collected from Imbak Canyon, Sabah, Malaysia. The structure of this compound was determined by the spectroscopic evidences using 1H- and 13C-NMR assigned with HSQC, HMBC, 1H-1H COSY and 1H-1H NOESY spectra, mass spectrum, and by comparison with reported data.

  8. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Audrey E. McCalley

    2014-06-01

    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  9. Enzymatic process for acylation of resveratrol at position 3

    OpenAIRE

    Torres, Pamela; Plou Gasca, Francisco José; Ballesteros Olmo, Antonio

    2008-01-01

    [EN] Enzymatic procedure for the regioselective acylation at position 3 of resveratrol utilising a vinyl ester and specific fungal and bacterial lipases, immobilised, as biocatalyst. The lipases utilised in said procedure come from bacteria or fungi selected from among Alcaligenes, Pseudomonas or Thermomyces.

  10. Chain elongation analog of resveratrol as potent cancer chemoprevention agent.

    Science.gov (United States)

    Kang, Yan-Fei; Qiao, Hai-Xia; Xin, Long-Zuo; Ge, Li-Ping

    2016-09-01

    Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism. PMID:27160168

  11. Antioxidant Therapy Against Trypanosome Infections: A Review Update.

    Science.gov (United States)

    Ibrahim, Mohammed Auwal; Bindawa Isah, Murtala; Abdullahi Salman, Abdulmalik

    2016-01-01

    Trypanosomiasis is a serious parasitic disease that affects humans and animals resulting in heavy health and economic burdens. Disturbance of redox equilibrium represents a classical challenge for both the host and the parasite during infections with either extracellular African or intracellular American trypanosomes species. This is in spite of existing detoxification mechanisms in both the host and the parasite for maintaining oxidative balance. However, oxidative stress still plays vital roles in the induction of numerous host-associated pathological damages such as anemia, hepatic and renal damages as well as cardiomyopathy while on the other hand, drugs that specifically induce oxidative stress to the parasite have been effective. Therefore, antioxidants have been deemed to play a role in modulating trypanosome infections. This review provides a current update on most of the studies conducted on the potential use of antioxidants as therapeutic agents against trypanosomes. The most frequently studied plant-derived phenolic antioxidants are resveratrol, cucurmin, gallic acid and quercetin while other antioxidants such as vitamins (A, C, E) and trace elements (selenium and iron) have been investigated. Some of the investigations monitored the direct trypanocidal or trypanostatic effects of the antioxidants while others studied the potentials of the antioxidants as adjuncts to trypanocidal drugs. So far, none of these approaches has sufficient data to allow a definite statement on the actual therapeutic potential of antioxidants in the treatment of clinical trypanosomiasis. Therefore, suggestions are made on the most therapeutically and clinically relevant role of antioxidants in trypanosome infections. PMID:27072713

  12. Resveratrol Prevents β-Cell Dedifferentiation in Nonhuman Primates Given a High-Fat/High-Sugar Diet

    Science.gov (United States)

    Fiori, Jennifer L.; Shin, Yu-Kyong; Kim, Wook; Krzysik-Walker, Susan M.; González-Mariscal, Isabel; Carlson, Olga D.; Sanghvi, Mitesh; Moaddel, Ruin; Farhang, Kathleen; Gadkaree, Shekhar K.; Doyle, Maire E.; Pearson, Kevin J.; Mattison, Julie A.; de Cabo, Rafael; Egan, Josephine M.

    2013-01-01

    Eating a “Westernized” diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6–1, NKX2–2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes. PMID:23884882

  13. Chemoprevention of HBV-related hepatocellular carcinoma by the combined product of resveratrol and silymarin in transgenic mice

    Directory of Open Access Journals (Sweden)

    Wen-Chuan Hsieh

    2013-09-01

    Full Text Available ABSTRACTBackground: Patients with chronic hepatitis B virus (HBV infection are at a high risk to develop hepatocellular carcinoma (HCC. Recently, metabolic syndrome has been found to carry a risk for HCC development. Considering the limitation of chemotherapeutic drugs for HCCs, the development of chemopreventive agents for high risk chronic HBV carriers is urgently demanded. In this study, we used combined silymarin and resveratrol extract which have been shown to exhibit biologic effects on activating peroxisome proliferator activated receptors (PPAR and inhibiting mTOR signaling in a transgenic mice model harboring HBV viral oncoproteins.Methods: The transgenic mice model harboring HBx and pre-S2 mutant constructs which develop HCC was adopted. First, we in vitro tested the ideal combination dosages of the silymarin and resveratrol product, and then we fed the natural product to the transgenic mice.The chemopreventive effects on preventing the development of HCC were evaluated.Results: MTT assay showed an enhanced effect of the combined silymarin and resveratrol product on the reduction of cell proliferation in two hepatoma cell lines, Huh-7 and Hep G2. In vitro reporter assay and Western blot analyses revealed that the combined product couldactivate PPAR/PGC-1 signaling and inhibit mTOR expression. In vivo, the combined products could significantly ameliorate fatty liver and reduce HCCs in transgenic miceharboring HBV oncoproteins.Conclusions: The combined silymarin and resveratrol product exhibits a synergistic effect on the reduction of HCC development in transgenic mice model and may represent a potential agent for the prevention of HCC in high risk chronic HBV carriers.Key words: HBV, HCC, Transgenic mice, Chemoprevention

  14. Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer

    International Nuclear Information System (INIS)

    Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro. A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP. Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line. These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted. NCT00256334

  15. Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats

    Indian Academy of Sciences (India)

    B RAGHUNATH REDDY; SWATI MAITRA; PRIYA JHELUM; K PRAVEEN KUMAR; PANKAJ K BAGUL; GAGANDEEP KAUR; SANJAY K BANERJEE; ARVIND KUMAR; SUMANA CHAKRAVARTY

    2016-09-01

    Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulinresistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarmingproportion, encompassing 95% of the total diabetic burden, probably due to economy-driven changes in lifestyle.Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore themolecular mechanisms underlying this comorbid conditions, we used Sprague–Dawley rats on high-fructose dietfor 8 weeks to induce prediabetic condition. Rats with this metabolic syndrome also showed hyper-anxiety when theywere subjected to anxiety-related behavioural assays. Rats were administered with resveratrol, an activator of sirtuins,and metformin, a standard antidiabetic drug, simultaneously with fructose. We observed that resveratrol was moreeffective in protecting from both the metabolic (prediabetic) and affective (anxiety) disorders than metformin.Molecular studies showed that recovery was associated with the upregulation of few nuclear sirtuins that actepigenetically – Sirt 1 and 7, which were significantly attenuated in the striatum of prediabetic rats. In conclusion,our study showed that hyper-anxiety associated with prediabetic condition is ameliorated by resveratrol throughmodulation of sirtuins, which is more or less similar to metformin.

  16. Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats.

    Science.gov (United States)

    Reddy, B Raghunath; Maitra, Swati; Jhelum, Priya; Kumar, K Praveen; Bagul, Pankaj K; Kaur, Gagandeep; Banerjee, Sanjay K; Kumar, Arvind; Chakravarty, Sumana

    2016-09-01

    Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95 percent of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore the molecular mechanisms underlying this comorbid conditions, we used Sprague-Dawley rats on high-fructose diet for 8 weeks to induce prediabetic condition. Rats with this metabolic syndrome also showed hyper-anxiety when they were subjected to anxiety-related behavioural assays. Rats were administered with resveratrol, an activator of sirtuins, and metformin, a standard antidiabetic drug, simultaneously with fructose. We observed that resveratrol was more effective in protecting from both the metabolic (prediabetic) and affective (anxiety) disorders than metformin. Molecular studies showed that recovery was associated with the upregulation of few nuclear sirtuins that act epigenetically - Sirt 1 and 7, which were significantly attenuated in the striatum of prediabetic rats. In conclusion, our study showed that hyper-anxiety associated with prediabetic condition is ameliorated by resveratrol through modulation of sirtuins, which is more or less similar to metformin. PMID:27581932

  17. In planta production of the highly potent resveratrol analogue pterostilbene via stilbene synthase and O-methyltransferase co-expression

    Energy Technology Data Exchange (ETDEWEB)

    Rimando A. M.; Liu C.; Pan, Z.; Polashock, J. J.; Dayan, F. E., Mizuno, C. S.; Snook, M. E.; Baerson, S. R.

    2012-04-01

    Resveratrol and related stilbenes are thought to play important roles in defence responses in several plant species and have also generated considerable interest as nutraceuticals owing to their diverse health-promoting properties. Pterostilbene, a 3,5-dimethylether derivative of resveratrol, possesses properties similar to its parent compound and, additionally, exhibits significantly higher fungicidal activity in vitro and superior pharmacokinetic properties in vivo. Recombinant enzyme studies carried out using a previously characterized O-methyltransferase sequence from Sorghum bicolor (SbOMT3) demonstrated its ability to catalyse the A ring-specific 3,5-bis-O-methylation of resveratrol, yielding pterostilbene. A binary vector was constructed for the constitutive co-expression of SbOMT3 with a stilbene synthase sequence from peanut (AhSTS3) and used for the generation of stably transformed tobacco and Arabidopsis plants, resulting in the accumulation of pterostilbene in both species. A reduced floral pigmentation phenotype observed in multiple tobacco transformants was further investigated by reversed-phase HPLC analysis, revealing substantial decreases in both dihydroquercetin-derived flavonoids and phenylpropanoid-conjugated polyamines in pterostilbene-producing SbOMT3/AhSTS3 events. These results demonstrate the potential utility of this strategy for the generation of pterostilbene-producing crops and also underscore the need for the development of additional approaches for minimizing concomitant reductions in key phenylpropanoid-derived metabolites.

  18. Resveratrol-3-O-glucuronide and resveratrol-4’-O-glucuronide reduce DNA strand breakage but not apoptosis in Jurkat T cells treated with camptothecin

    Science.gov (United States)

    Resveratrol has been reported to inhibit or induce DNA damage depending upon the type of cell and experimental conditions. Dietary resveratrol is present in the body mostly as metabolites and little is known about the activities of these metabolic products. We evaluated physiologically obtainable ...

  19. Resveratrol attenuates inflammation and oxidative stress in epididymal white adipose tissue: implications for its involvement in improving steroidogenesis in diet-induced obese mice.

    Science.gov (United States)

    Lv, Zheng-mei; Wang, Qi; Chen, Yuan-hua; Wang, Sheng-hua; Huang, Dao-qi

    2015-04-01

    Chronic, low-grade systemic inflammation has been shown to play an important role in the development of obesity-related complications. Epididymal white adipose tissue (WAT) can influence testicular function through its endocrine function. The purpose of this study was to assess the effects of resveratrol on the epididymal WAT inflammatory response and on testicular steroidogenesis in obese individuals. Seven-week-old male C57BL/6J mice were fed a high-calorie and high-cholesterol diet (HCD group) or HCD supplemented with resveratrol (HCD+Res group) for 18 weeks. As we previously showed that resveratrol protects against Leydig cell steroidogenesis in HCD-induced obese mice, this study assessed macrophage infiltration in fat depots by measuring crown-like structure (CLS) density. Histological analysis showed that adipocyte size was significantly smaller and CLSs were less numerous in the HCD+Res group than the HCD group (P < 0.01). Additionally, resveratrol supplementation decreased Nfkb1 expression (P < 0.01) and increased the IκB-α protein abundance (P < 0.01) in epididymal WAT. Consistent with this alteration in NF-κB signaling, the expression of two classic proinflammatory cytokines, TNF-α (Tnfa) and IL-1β (Il1b), were significantly decreased in the HCD+Res group compared with the HCD group (P < 0.01). Significant differences were also found in the expression of sirtuin1 (Sirt1) (P < 0.01) and manganese superoxide dismutase (Sod2) (P < 0.01) between the HCD and HCD+Res groups. Our data suggest that resveratrol can attenuate obesity-induced inflammation and oxidative stress in epididymal WAT, which partly accounts for its beneficial effects in testicular steroidogenesis.

  20. Physicochemical Changes and Glycation Reaction in Intermediate-Moisture Protein-Sugar Foods with and without Addition of Resveratrol during Storage.

    Science.gov (United States)

    Sheng, Zhanwu; Gu, Mantun; Hao, Wangjun; Shen, Yixiao; Zhang, Weimin; Zheng, Lili; Ai, Binling; Zheng, Xiaoyan; Xu, Zhimin

    2016-06-22

    An intermediate-moisture food (IMF) model consisting of whey protein isolate and glucose and an IMF model fortified with resveratrol were used to study the effect of resveratrol on physicochemical changes and glycation of protein-sugar-rich foods during storage. The water activity (aw) of the storage was controlled at 0.75 or 0.56. The browning rate or hardness of fortified IMFs was significantly lower than that of IMFs after 45-day storage. The rate of Maillard reaction in the samples stored at aw 0.56 was higher than that of samples stored at aw 0.75. The fortified IMFs had lower levels of AGEs (advanced glycation end products), CML (N(ε)-(carboxymethyl)-l-lysine), and insoluble protein during storage. The inhibition capability of resveratrol against glycation was also confirmed by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), liquid chromatography mass spectrometry (LC-MS), and Fourier transform infrared spectroscopy (FTIR) analysis to monitor glycated proteins and protein aggregation in the samples. The results of this study suggested that resveratrol could be used as an inhibitor to reduce the formation of undesirable AGEs and other Maillard reaction products in foods during storage. PMID:27218138

  1. Effect of Resveratrol Supplementation on the SNARE Proteins Expression in Adipose Tissue of Stroptozotocin-Nicotinamide Induced Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Azam Rezaei Farimani

    2015-05-01

    Full Text Available Background: Glucose uptake by muscles and fat cells is carried out by the GLUT4 system. Isoforms of the SNAP23, syntaxin-4 and VAMP-2 play an important role in regulating GLUT-4 trafficking and fusion in adipocytes. The changes of SNARE proteins levels and thus impaired GLUT-4 displacement can be one of the etiological causes of type 2 diabetes. Due to changes in the expression of these proteins in diabetes, the aim of this study was to investigate the effect of the natural compound resveratrol with anti-diabetic properties on impaired expression of SNARE proteins in type 2 diabetes. Methods: Forty male Wistar rats were used in this study. Type 2 diabetes was induced by administering a single dose of streptozotocin and nicotinamide. The expression of SNAP-23, syntaxin-4 and VAMP-2 proteins were assessed using real-time qRT-PCR. Also, some biochemical parameters were examined, including fasting blood glucose, insulin levels and insulin resistance. Results: The results of this study showed that, resveratrol supplementation increased blood insulin level, reduced the fasting blood glucose, and improved the insulin resistance. In addition, resveratrol supplementation increased the expression of SNAP-23, syntaxin-4 and VAMP-2 proteins that involved in GLUT-4 transport in adipose tissue of diabetic rats. Conclusion: Final results showed that SNARE proteins expression is significantly reduced in diabetic rats and treatment with resveratrol supplementation is associated with the increased expression of these proteins.

  2. Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high-resolution mass spectrometry.

    Science.gov (United States)

    Etxeberria, Usune; Arias, Noemi; Boqué, Noemí; Romo-Hualde, Ana; Macarulla, M Teresa; Portillo, María P; Milagro, Fermín I; Martínez, J Alfredo

    2015-08-01

    Faecal non-targeted metabolomics deciphers metabolic end-products resulting from the interactions among food, host genetics, and gut microbiota. Faeces from Wistar rats fed a high-fat sucrose (HFS) diet supplemented with trans-resveratrol and quercetin (separately or combined) were analysed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Metabolomics in faeces are categorised into four clusters based on the type of treatment. Tentative identification of significantly differing metabolites highlighted the presence of carbohydrate derivatives or conjugates (3-phenylpropyl glucosinolate and dTDP-D-mycaminose) in the quercetin group. The trans-resveratrol group was differentiated by compounds related to nucleotides (uridine monophosphate and 2,4-dioxotetrahydropyrimidine D-ribonucleotide). Marked associations between bacterial species (Clostridium genus) and the amount of some metabolites were identified. Moreover, trans-resveratrol and resveratrol-derived microbial metabolites (dihydroresveratrol and lunularin) were also identified. Accordingly, this study confirms the usefulness of omics-based techniques to discriminate individuals depending on the physiological effect of food constituents and represents an interesting tool to assess the impact of future personalized therapies.

  3. Resveratrol and piceid metabolites and their fat-reduction effects in zebrafish larvae.

    Science.gov (United States)

    Pardal, David; Caro, Mercedes; Tueros, Itziar; Barranco, Alejandro; Navarro, Virginia

    2014-02-01

    Resveratrol, a polyphenolic phytoalexin found in many plants, has been reported to have antiobesogenic effects in several animal and in vitro models. Zebrafish present several technical advantages that place them at an interesting, halfway point between in vitro and rodent models. The aim of the present work was to evaluate the metabolization of resveratrol and its glucoside (piceid) in zebrafish and their ability to induce the consumption of fat reserve in zebrafish larvae. Resveratrol and piceid were both able to reduce yolk sac fat content depending on the dose tested. Furthermore, resveratrol showed a potent and rapid action, whereas piceid needed more time and higher doses to be as effective as resveratrol. In accordance with other animal models and humans, the principal metabolites found in zebrafish larvae were monoglucoronide and monosulfate forms of resveratrol. In conclusion, zebrafish are a potentially excellent animal model for polyphenol research as they present several advantageous characteristics for efficacy screening and metabolomic studies before rodents.

  4. Protective Action of Resveratrol in Human Skin: Possible Involvement of Specific Receptor Binding Sites

    OpenAIRE

    Stéphane Bastianetto; Yvan Dumont; Albert Duranton; Freya Vercauteren; Lionel Breton; Rémi Quirion

    2010-01-01

    BACKGROUND: Resveratrol is a plant-derived polyphenol with purported protecting action on various disorders associated with aging. It has been suggested that resveratrol could exert its protective action by acting on specific plasma membrane polyphenol binding sites (Han Y.S., et al. (2006) J Pharmacol Exp Ther 318:238-245). The purpose of this study was to investigate, in human skin, the possible existence of specific binding sites that mediate the protective action of resveratrol. METHODS A...

  5. Polyphenolic composition of grape stem extracts affects antioxidant activity in endothelial and muscle cells.

    Science.gov (United States)

    Goutzourelas, Nikolaos; Stagos, Dimitrios; Spanidis, Ypatios; Liosi, Maria; Apostolou, Anna; Priftis, Alexandros; Haroutounian, Serko; Spandidos, Demetrios A; Tsatsakis, Aristidis M; Kouretas, Demetrios

    2015-10-01

    The aim of the present study was the assessment of the antioxidant effects of polyphenolic extracts derived from the stems of three Greek grape varieties (Moshomayro, Mavrotragano and Mandilaria) in endothelial (EA.hy926) and muscle (C2C12) cells. We also investigated the effects of the polyphenolic composition on the antioxidant effects of the grape stem extracts. For this purpose, the endothelial and muscle cells were treated with low non-cytotoxic concentrations of the extracts for 24 h in order to assess the effects of the extracts on cellular redox status using oxidative stress biomarkers. The oxidative stress markers were thiobarbituric acid reactive substances (TBARS), protein carbonyl (CARB) levels, reactive oxygen species (ROS) levels and glutathione (GSH) levels. The results revealed that treatment of the EA.hy926 cells with Mandilaria extract significantly decreased the TBARS levels by 14.8% and the CARB levels by 25.9 %, while it increased the GSH levels by 15.8% compared to the controls. Moreover, treatment of the EA.hy926 cells with Mavrotragano extract significantly increased the GSH levels by 20.2%, while it significantly decreased the TBARS and CARB levels by 12.5% and 16.6%, respectively. Treatment of the C2C12 cells with Mandilaria extract significantly decreased the TBARS levels by 47.3 %, the CARB levels by 39.0 % and the ROS levels by 21.8%, while it increased the GSH levels by 22.6% compared to the controls. Moreover, treatment of the C2C12 cells with Mavrotragano significantly decreased the TBARS, CARB and ROS levels by 36.2%, 35.9% and 16.5%, respectively. In conclusion, to the best of our knowledgel, our results demonstrate for the first time that treatment with grape stem extracts at low concentrations improves the redox status of endothelial and muscle cells. Thus, grape stem extracts may be used for developing antioxidant food supplements or biofunctional foods. However, it was also found that the polyphenolic composition of grape stem

  6. Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Haibin; Shang, Linshan; Li, Xi; Zhang, Xiyu; Gao, Guimin; Guo, Chenhong; Chen, Bingxi; Liu, Qiji [Key Laboratory of Experimental Teratology, MOE, Institute of Molecular Medicine and Genetics, Shandong University, 44 Wen Hua Xi Lu, Jinan, Shandong 250012 (China); Gong, Yaoqin, E-mail: yxg8@sdu.edu.cn [Key Laboratory of Experimental Teratology, MOE, Institute of Molecular Medicine and Genetics, Shandong University, 44 Wen Hua Xi Lu, Jinan, Shandong 250012 (China); Shao, Changshun, E-mail: shao@biology.rutgers.edu [Key Laboratory of Experimental Teratology, MOE, Institute of Molecular Medicine and Genetics, Shandong University, 44 Wen Hua Xi Lu, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)

    2009-10-15

    Resveratrol has been shown to possess many health-benefiting effects, including the promotion of bone formation. In this report we investigated the mechanism by which resveratrol promotes osteoblastic differentiation from pluripotent mesenchymal cells. Since Wnt signaling is well documented to induce osteoblastogenesis and bone formation, we characterized the factors involved in Wnt signaling in response to resveratrol treatment. Resveratrol treatment of mesenchymal cells led to an increase in stabilization and nuclear accumulation of {beta}-catenin dose-dependently and time-dependently. As a consequence of the increased nuclear accumulation of {beta}-catenin, the ability to activate transcription of {beta}-catenin-TCF/LEF target genes that are required for osteoblastic differentiation was upregulated. However, resveratrol did not affect the initial step of the Wnt signaling pathway, as resveratrol was as effective in upregulating the activity of {beta}-catenin in cells in which Lrp5 was knocked down as in control cells. In addition, while conditioned medium enriched in Wnt signaling antagonist Dkk1 was able to inhibit Wnt3a-induced {beta}-catenin upregulation, this inhibitory effect can be abolished in resveratrol-treated cells. Furthermore, we showed that the level of glycogen synthase kinase 3{beta} (GSK-3{beta}), which phosphorylates and destabilizes {beta}-catenin, was reduced in response to resveratrol treatment. The phosphorylation of GSK-3{beta} requires extracellular signal-regulated kinase (ERK)1/2. Together, our data indicate that resveratrol promotes osteoblastogenesis and bone formation by augmenting Wnt signaling.

  7. Treatment strategies for high resveratrol induction in Vitis vinifera L. cell suspension culture

    Directory of Open Access Journals (Sweden)

    Thu V. Vuong

    2014-06-01

    Full Text Available Bioprocesses capable of producing large scales of resveratrol at nutraceutical grade are in demand. This study herein investigated treatment strategies to induce the production of resveratrol in Vitis vinifera L. cell suspension cultures. Among seven investigated elicitors, jasmonic acid (JA, salicylic acid, β-glucan (GLU, and chitosan enhanced the production of intracellular resveratrol manyfold. The combined treatment of JA and GLU increased extracellular resveratrol production by up to tenfold. The application of Amberlite XAD-7 resin for in situ removal and artificial storage of secreted resveratrol further increased resveratrol production by up to four orders of magnitude. The level of resveratrol produced in response to the combined treatment with 200 g/L XAD-7, 10 μM JA and 1 mg/mL GLU was approximately 2400 mg/L, allowing the production of resveratrol at an industrial scale. The high yield of resveratrol is due to the involvement of a number of mechanisms working in concert.

  8. Effect of a quality-controlled fermented nutraceutical on skin aging markers: An antioxidant-control, double-blind study

    OpenAIRE

    BERTUCCELLI, GIUSEPPE; Zerbinati, Nicola; Marcellino, Massimiliano; NANDA KUMAR, NAVALPUR SHANMUGAM; He, Fang; TSEPAKOLENKO, VLADIMIR; Cervi, Joseph; LORENZETTI, ALDO; Marotta, Francesco

    2016-01-01

    The aim of the present study was to determine whether oral supplementation with a fermented papaya preparation (FPP-treated group) or an antioxidant cocktail (antioxidant-control group, composed of 10 mg trans-resveratrol, 60 µg selenium, 10 mg vitamin E and 50 mg vitamin C) was able to improve the skin antioxidant capacity and the expression of key skin genes, while promoting skin antiaging effects. The study enrolled 60 healthy non-smoker males and females aged 40–65 years, all of whom show...

  9. Determinação de resveratrol em sucos de uva no Brasil Determination of resveratrol in grape juice produced in Brazil

    Directory of Open Access Journals (Sweden)

    Cláudia K. Sautter

    2005-09-01

    Full Text Available A detecção de resveratrol em vinhos vem sendo estudada mais intensamente nos últimos anos. O isômero trans-resveratrol tem reconhecidas atividades biológicas, e algumas delas são de uso terapêutico, tais como ação antiinflamatória, inibição da enzima lipoxigenase e ação anticarcinogênica in vitro. A presença do composto resveratrol (4,3',5'-trihidroxiestilbeno, em seus isômeros (trans e cis, foi determinada nos diferentes tipos de sucos de uva produzidos no Brasil. Além destes, também foram quantificados os polifenóis totais, acidez, açúcares redutores, sólidos solúveis e densidade, em conformidade com a legislação vigente. O resveratrol foi quantificado por cromatografia líquida de alta eficiência segundo SOUTO et al. [23], com adaptação da temperatura para 50° C. Foi detectada a presença de trans-resveratrol em todos os sucos analisados na concentração de 0,19mg.L-1 a 0,90mg.L-1 e o isômero cis-resveratrol foi de 0,07 a 1,59mg.L-1 .The resveratrol detection in wines has been studied more intensely in the last years. The isomeric trans-resveratrol has recognized biological activities, and some of them are therapeutic, such as anti-inflammatory action, enzyme lipoxigenase inhibition and anti-carcinogenic action in vitro. The presence of resveratrol (4,3',5'-trihydroxystilbene, trans and cis isomers, was investigated in industrial grape juices produced in Brazil. Additionally, total phenols, acidity, reducing sugars, soluble solids and specific gravity of samples were determined in accordance with law. Resveratrol was determined by high performance liquid chromatography by SOUTO et al. [23], adapted to the temperature of 50°C. Trans and cis-resveratrol were found in all the juices analyzed, tran-resveratrol in the concentration range of 0.19 to 0.90mg.L-1 and cis-resveratrol in the concentration range of 0.07 to 1.59mg.L-1.

  10. Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies.

    Science.gov (United States)

    Singh, Gurinder; Pai, Roopa S

    2015-01-01

    Trans-resveratrol (t-RVT) is a potent antioxidant. By virtue of extensive pre-systemic metabolism and existence of enterohepatic recirculation, t-RVT bioavailability is almost zero. The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides (LCTs) of t-RVT in an attempt to circumvent such obstacles. Equilibrium solubility studies indicated the choice of Lauroglycol FCC as lipid, and of Labrasol and Transcutol P as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X(1)) and surfactant (X(2)) as the critical factor variables. The SNEDDS were optimized using 3(2) central composite design (CCD) and the optimized formulation (OPT) located using overlay plot. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the SNEDDS. Optimized formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT. Augmentation in the values of K(a) (3.29-fold) and AUC (4.31-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT compared with pure drug. In situ perfusion (SPIP) studies in Wistar rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the pure drug. Successful establishment of level A of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The present study, therefore, reports the successful development of SNEDDS with distinctly enhanced bioavailability of t-RVT. PMID:24512464

  11. Inhibition of caspases and intracellular free Ca2+ concentrations are involved in resveratrol protection against apoptosis in rat primary neuron cultures

    Institute of Scientific and Technical Information of China (English)

    Qi-hai GONG; Qian WANG; Jing-shan SHI; Xie-nan HUANG; Qiong LIU; Hu MA

    2007-01-01

    Aim:To investigate the influence of resveratrol (Res),a nutritional antioxidant,on the inhibition of apoptosis in rat primary neuron cultures. Methods:The cultured cortical neurons of neonatal Sprague-Dawley rats were pretreated with Res (0. 1,1.0,and 10.0μmol/L) and oxygen-glucose deprivation/reperfusion (OGD/RP) with oxygen and glucose were initiated at d 10 in vitro. Neuronal apoptosis was determined by flow cytometry,and morphological changes of neurons were observed by an electron microscope. For the mechanism studies,the intracellular free calcium concentration ([Ca2+]i) and the transcription of caspases-3 and -12 in neurons were detected by Fura 2/AM loading and real-time RT-PCR,respectively.Results:OGD/RP insult could induce an increase in the apoptotic rate of neurons (from 11.1% to 49.0%),and elicit an obvious morphological change in neurons;pretreatments with Res (0.1,1.0,and 10.0 μmol/L,respectively) significantly reduced the elevated rate of apoptosis to 41.7%,40.8%,and 37.4%,respectively,and ameliorated the neuronal morphological injury. Similarly,the OGD/RP insult obviously elicited the elevated levels of the [Ca2+]i and the expressions of caspases-3 and-12 mRNA in neurons. Res pretreatments markedly depressed the neuronal abnormal elevation of [Ca2+]i and the overexpression of caspases-3 and -12 mRNA in a concentration-dependent manner. Conclusion:Res can attenuate the rat cortical neuronal apoptosis induced by OGD/RP. The mechanisms are,at least partly,due to the inhibition of the calcium overload and the overexpression of caspases-3 and - 12 mRNA.

  12. Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Zhen; Xu, Michael S.; Barnett, Tamara L. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Xu, C. Wilson, E-mail: wxu@nvcancer.org [Nevada Cancer Institute, Las Vegas, NV 89135 (United States)

    2011-04-08

    Research highlights: {yields} Resveratrol induces cellular senescence in glioma cell. {yields} Resveratrol inhibits mono-ubiquitination of histone H2B at K120. {yields} Depletion of RNF20, phenocopies the inhibitory effects of resveratrol. {yields} Mono-ubiquitination of histone H2B at K120 is a novel target of resveratrol. {yields} RNF20 inhibits cellular senescence in proliferating glioma cells. -- Abstract: Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol naturally occurring in grapes and other plants, has cancer chemo-preventive effects and therapeutic potential. Although resveratrol modulates multiple pathways in tumor cells, how resveratrol or its affected pathways converge on chromatin to mediate its effects is not known. Using glioma cells as a model, we showed here that resveratrol inhibited cell proliferation and induced cellular hypertrophy by transforming spindle-shaped cells to enlarged, irregular and flatten-shaped ones. We further showed that resveratrol-induced hypertrophic cells expressed senescence-associated-{beta}-galactosidase, suggesting that resveratrol-induced cellular senescence in glioma cells. Consistent with these observations, we demonstrated that resveratrol inhibited clonogenic efficiencies in vitro and tumor growth in a xenograft model. Furthermore, we found that acute treatment of resveratrol inhibited mono-ubiquitination of histone H2B at K120 (uH2B) in breast, prostate, pancreatic, lung, brain tumor cells as well as primary human cells. Chronic treatment with low doses of resveratrol also inhibited uH2B in the resveratrol-induced senescent glioma cells. Moreover, we showed that depletion of RNF20, a ubiquitin ligase of histone H2B, inhibited uH2B and induced cellular senescence in glioma cells in vitro, thereby recapitulated the effects of resveratrol. Taken together, our results suggest that uH2B is a novel direct or indirect chromatin target of resveratrol and RNF20 plays an important role in inhibiting cellular

  13. Synthesis of Resveratrol and Resveratrol Trinicotinate%白藜芦醇及白藜芦醇烟酸酯的合成

    Institute of Scientific and Technical Information of China (English)

    张学景; 朱杰; 熊晓云; 邹永; 林慧贞

    2004-01-01

    目的合成一种前药白藜芦醇烟酸酯.方法在金属锂片和催化量的萘的存在下, 3,5-二甲氧基苯甲醛与对甲氧基苯甲醇的三甲基硅醚反应经过一系列转变得到白藜芦醇,白藜芦醇与烟酰氯反应得到白藜芦醇烟酸酯.结果设计并合成了白藜芦醇烟酸酯.结论提供了一种合成白藜芦醇及白藜芦醇烟酸酯的方法,采用KHSO4脱水可选择性的得到反式产物.%Aim To synthesize a new prodrug, resveratrol trinicotinate.Methods In presence of lithium and a catalytic amount of naphthalene, the reaction of p-methoxybenzyl trimethylsilyl ether and 3,5-dimethoxylbenzaldehyde gave resveratrol after a series of translation.Resveratrol trinicotinate was obtained by the reaction of resveratrol and nicotinoyl chloride hydrochloride.Results A mutual prodrug resveratrol trinicotinate was designed and synthesized.Conclusion A novel method for synthesis of resveratrol and resveratrol trinicotinate has been afforded.The E-isomer is selectivily obtained by dehydration of the compound 2 with KHSO4.

  14. Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity

    Institute of Scientific and Technical Information of China (English)

    Chun-yan SUN; Yu HU; Tao GUO; Hua-fang WANG; Xiao-ping ZHANG; Wen-juan HE; Hao TAN

    2006-01-01

    Aim: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. Methods: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-xL, XIAP and Bax protein were detected using Western blotting analysis. Results: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-xL and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64±8 μmol/L, 93±11 μmol/L, and 153±11 μmol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. Conclusion: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.

  15. Cardiac energy metabolism and oxidative stress biomarkers in diabetic rat treated with resveratrol.

    Science.gov (United States)

    Carolo dos Santos, Klinsmann; Pereira Braga, Camila; Octavio Barbanera, Pedro; Seiva, Fábio Rodrigues Ferreira; Fernandes Junior, Ary; Fernandes, Ana Angélica Henrique

    2014-01-01

    Resveratrol (RSV), polyphenol from grape, was studied to evaluate its effects on calorimetric parameters, energy metabolism, and antioxidants in the myocardium of diabetic rats. The animals were randomly divided into four groups (n = 8): C (control group): normal rats; C-RSV: normal rats receiving RSV; DM: diabetic rats; and DM-RSV: diabetics rats receiving RSV. Type 1 diabetes mellitus was induced with administration of streptozotocin (STZ; 60 mg(-1) body weight, single dose, i.p.). After 48 hours of STZ administration, the animals received RSV (1.0 mg/kg/day) for gavage for 30 days. Food, water, and energy intake were higher in the DM group, while administration of RSV caused decreases (pdiabetic rats showed higher serum-free fatty acid, which was normalized with RSV. Oxygen consumption (VO2) and carbon dioxide production (VCO2) decreased (plactate dehydrogenase compared to the DM-RSV group. Myocardial protein carbonyl was increased in the DM group. RSV increased reduced glutathione in the cardiac tissue of diabetic animals. The glutathione reductase activity was higher in the DM-RSV group compared to the DM group. In conclusion, diabetes is accompanied by cardiac energy metabolism dysfunction and change in the biomarkers of oxidative stress. The cardioprotective effect may be mediated through RVS's ability to normalize free fatty acid oxidation, enhance utilization glucose, and control the biomarkers' level of oxidative stress under diabetic conditions. PMID:25050809

  16. The Grape Component Resveratrol Interferes with the Function of Chemoattractant Receptors on Phagocytic Leukocytes

    Institute of Scientific and Technical Information of China (English)

    Hengyi Tao; Chunfu Wu; Ye Zhou; Wanghua Gong; Xia Zhang; Pablo Iribarren; Yuqing Zhao; Yingying Le; Jiming Wang

    2004-01-01

    Resveratrol (3, 5, 4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant receptors, which play important roles in inflammation and immune responses.RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations, RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for formylpeptide receptor FPR, and Aβ42, an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-κB induced by formylpeptide receptor agonists. These results suggest that the inhibition of the function of chemoattractant receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of formylpeptide receptors contributes to the pathogenic processes. Cellular & Molecular Immunology. 2004;1(1):50-56.

  17. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    International Nuclear Information System (INIS)

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  18. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    Energy Technology Data Exchange (ETDEWEB)

    Sebastià, N., E-mail: natividad.sebastia@uv.es [Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Montoro, A. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Hervás, D. [Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Pantelias, G.; Hatzi, V.I. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research “Demokritos”, Aghia Paraskevi, Athens (Greece); Soriano, J.M. [Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia (Spain); Villaescusa, J.I. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); and others

    2014-08-15

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  19. Resveratrol Induces Glioma Cell Apoptosis through Activation of Tristetraprolin

    OpenAIRE

    Ryu, Jinhyun; Yoon, Nal Ae; Seong, Hyemin; Jeong, Joo Yeon; Kang, Seokmin; Park, Nammi; Choi, Jungil; Lee, Dong Hoon; Roh, Gu Seob; Kim, Hyun Joon; Cho, Gyeong Jae; Choi, Wan Sung; Park, Jae-Yong; Park, Jeong Woo; Kang, Sang Soo

    2015-01-01

    Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of AREs-containing mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4′-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetr...

  20. Resveratrol tetramer of hopeaphenol isolated from Shorea johorensis (Dipterocarpaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Aisha, Farra; Din, Laily B.; Yaacob, W. A. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor (Malaysia)

    2014-09-03

    Hopeaphenol (1) as a resveratrol tetramer was isolated from the bark of Shorea johorensis collected from Imbak Canyon, Sabah, Malaysia. The structure of this compound was determined by the spectroscopic evidences using {sup 1}H- and {sup 13}C-NMR assigned with HSQC, HMBC, {sup 1}H−{sup 1}H COSY and {sup 1}H−{sup 1}H NOESY spectra, mass spectrum, and by comparison with reported data.

  1. Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals

    OpenAIRE

    Osman, Abdel-Moneim M; Al-Harthi, Sameer E.; AlArabi, Ohoud M; Elshal, Mohamed F.; Ramadan, Wafaa S.; Alaama, Mohamed N; Al-Kreathy, Huda M; Zoheir A Damanhouri; Osman, Osman H

    2013-01-01

    Background Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer drug used in the treatment of variety of cancers .Its use is limited by its cardiotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and at the same time its protective effect against DOX-induced cardiotoxicity in rats. Methods Ehrlich ascites carcinoma bearing m...

  2. Antiglycation and antioxidant activities of oxyresveratrol extracted from the heartwood of Artocarpus lakoocha Roxb.

    OpenAIRE

    Pimporn Leelapornpisid

    2010-01-01

    From the heartwood of Artocarpus lakoocha, oxyresveratrol was isolated with a yield of 10%. The isolated oxyresveratrol showed strong antiglycation and antioxidant activities. The IC50 value for antiglycation was 2.0±0.03 μg/ml (five times higher than that of aminoguanidine), and the IC50 values for antioxidation were 0.1±0.01 mg/ml (DPPH method) and 0.43±0.03 mg/ml (TBARS method), which were nearly twice as strong as those of resveratrol.

  3. Resveratrol: A Sirtuin Activator and The Fountain of Youth

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2015-04-01

    Full Text Available BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life. CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan. SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.” KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator.

  4. Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells.

    Science.gov (United States)

    Barbosa, João P; Neves, Ana R; Silva, Andreia M; Barbosa, Mário A; Reis, M Salette; Santos, Susana G

    2016-01-01

    Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter <200 nm and highly negative zeta potential (about -30 mV). When DCs were placed in contact with NLC, imaging flow cytometry clearly showed that DCs efficiently internalized FITC-NLC, with nearly 100% of cells internalizing nanoparticles upon 1 hour of incubation. Both immature and mature DCs internalized NLC to high and comparable levels, and without cytotoxicity. Stimulating DC with TNF-α in the presence of rsv-NLC revealed that, using these nanoparticles, very small concentrations of rsv were sufficient to significantly decrease surface expression of activation marker CD83 (5 µM) and major histocompatibility complex-class II molecule human leukocyte antigen - antigen D related (10 µM), both upregulated in response to TNF-α stimulation. Rsv-NLC were compared with free rsv; at 5 µM, rsv-NLC were able to inhibit nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed

  5. What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

    DEFF Research Database (Denmark)

    Vang, Ole; Ahmad, Nihal; Baile, Clifton A.;

    2011-01-01

    of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search...

  6. Preparation of resveratrol-loaded nanoporous silica materials with different structures

    Energy Technology Data Exchange (ETDEWEB)

    Popova, Margarita, E-mail: mpopova@orgchem.bas.bg [Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia (Bulgaria); Szegedi, Agnes [Research Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, Hungarian Academy of Sciences, 1117 Budapest, Magyar tudósok körútja 2. (Hungary); Mavrodinova, Vesselina [Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia (Bulgaria); Novak Tušar, Natasa [National Institute of Chemistry, Ljubljana (Slovenia); Mihály, Judith; Klébert, Szilvia [Research Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, Hungarian Academy of Sciences, 1117 Budapest, Magyar tudósok körútja 2. (Hungary); Benbassat, Niko; Yoncheva, Krassimira [Faculty of Pharmacy, 2 Dunav Str., 1000 Sofia (Bulgaria)

    2014-11-15

    Solid, nanoporous silica-based spherical mesoporous MCM-41 and KIL-2 with interparticle mesoporosity as well as nanosized zeolite BEA materials differing in morphology and pore size distribution, were used as carriers for the preparation of resveratrol-loaded delivery systems. Two preparation methods have been applied: (i) loading by mixing of resveratrol and mesoporous carrier in solid state and (ii) deposition in ethanol solution. The parent and the resveratrol loaded carriers were characterized by XRD, TEM, N2 physisorption, thermal analysis, and FT-IR spectroscopy. The influence of the support structure on the adsorption capacity and the release kinetics of this poorly soluble compound were investigated. Our results indicated that the chosen nanoporous silica supports are suitable for stabilization of trans-resveratrol and reveal controlled release and ability to protect the supported compound against degradation regardless of loading method. The solid-state dry mixing appears very effective for preparation of drug formulations composed of poorly soluble compound. - Graphical abstract: trans-Resveratrol was stabilized in the pores of BEA zeolite, MCM-41and KIL2 mesoporous silicas. - Highlights: • BEA, KIL-2 and MCM-41 materials were used as carriers for resveratrol loading. • Resveratrol encapsulation in ethanol solution and solid state procedure were applied. • The solid-state preparation appears very effective for stabilization of trans-resveratrol.

  7. Resveratrol acts as a natural profungicide and induces self-intoxication by a specific laccase

    NARCIS (Netherlands)

    Schouten, A.; Wagemakers, L.; Stefanato, F.L.; Kaaij, van der R.M.; Kan, van J.A.L.

    2002-01-01

    The grapevine (Vitis) secondary metabolite resveratrol is considered a phytoalexin, which protects the plant from Botrytis cinerea infection. Laccase activity displayed by the fungus is assumed to detoxify resveratrol and to facilitate colonization of grape. We initiated a functional molecular genet

  8. Microbial metabolism Part 14 Isolation and bioactivity evaluation of microbial metabolites of resveratrol

    Science.gov (United States)

    The fungi, Beauveria bassiana (ATCC 13144) and Penicillium chrysogenium (ATCC 9480) transformed resveratrol (1) to resveratrol-3-O-sulfate (4). The former, in addition, gave 5-methoxyresveratrol-3-O-ß-glucoside (2) with the latter yielding 5-methoxyresveratrol-3-O-sulfate (3). The structures were es...

  9. Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat

    DEFF Research Database (Denmark)

    Breinholt, Vibeke M.; Mølck, Anne-Marie; Svendsen, Gitte Winkel;

    2003-01-01

    The potential beneficial or adverse affect of prolonged dietary administration of moderate to high doses (1-100 mg/kg diet) of the antioxidants, lycopene, quercetin and resveratrol or a mixture of lycopene and quercetin was investigated in male F344 rats. Selected markers for toxicity and defense...

  10. Determination of resveratrol in red wine by solid phase extraction-flow injection chemiluminescence method

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A sensitive flow injection chemiluminescence method has been developed for the detection of resveratrol in red wine based on the fact that resveratrol can greatly enhance chemiluminescence reaction between KMnO4 and HCHO in sulfuric acid medium.Analytes were pre-concentrated on solid sorbents (C18 solid-phase extraction cartridges). Under the optimum conditions, the proposed method allows the measurement of resveratrol over the range of 1.32 × 10-s to 1.32 × 10-5 mol/L with a detection limit of 3.30 × 10-9 mol/L, and the relative standard deviation for 1.32 × 10-5 mol/L resveratrol (n = 11 ) is 3.8%. This method has been successfully applied for the determination of the resveratrol in red wine. Furthermore, the possible reaction mechanism was also discussed.

  11. Physical methods of resveratrol induction in grapes and grape products - a review

    International Nuclear Information System (INIS)

    Trans-resveratrol ((E)-3,4',5-trihydroxystilbene) is a substance that is produced by a large number of plants as a phytoalexin. Resveratrol has been credited as being potentially responsible for the ''French paradox'' - the observation that the French have a relatively low incidence of coronary heart disease, even though their diet is high in saturated fats. This review deals with the methods serving for the increase of the resveratrol content in wine products - wine and grape juices. The methods reviewed are UV irradiation of grapes and ozonisation of grapes. The discussed methods describe the ways of increasing resveratrol contents in grapes and wine using ''natural'' methods. Resveratrol is increased endogenously and therefore, it need not be declared as the added substance on the product labels

  12. Effects of Resveratrol on Daily Rhythms of Locomotor Activity and Body Temperature in Young and Aged Grey Mouse Lemurs

    Directory of Open Access Journals (Sweden)

    Fabien Pifferi

    2013-01-01

    Full Text Available In several species, resveratrol, a polyphenolic compound, activates sirtuin proteins implicated in the regulation of energy balance and biological clock processes. To demonstrate the effect of resveratrol on clock function in an aged primate, young and aged mouse lemurs (Microcebus murinus were studied over a 4-week dietary supplementation with resveratrol. Spontaneous locomotor activity and daily variations in body temperature were continuously recorded. Reduction in locomotor activity onset and changes in body temperature rhythm in resveratrol-supplemented aged animals suggest an improved synchronisation on the light-dark cycle. Resveratrol could be a good candidate to restore the circadian rhythms in the elderly.

  13. Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

    Science.gov (United States)

    Murakami, Itsuo; Chaleckis, Romanas; Pluskal, Tomáš; Ito, Ken; Hori, Kousuke; Ebe, Masahiro; Yanagida, Mitsuhiro; Kondoh, Hiroshi

    2014-01-01

    Resveratrol (RESV) is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.

  14. Effects of resveratrol, curcumin and their derivatives on the activation of microglia induced by LPS

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-yu; MENG Xue-lian; ZHANG Li-jia; CHEN Guo-liang; WU Chun-fu

    2008-01-01

    Objective To determine the inhibitory effects of 21 resveratrol derivatives and 3 natural eureumiholds on lipopolysaccharide (LPS)-induced Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) production in mieroglia and their structure-activity relationships. Methods Cell viability was evaluated by the MTT reduction assay. Accumulation of nitrite (NO2-) in culture supernatant fluids was measured by the Griess reaction. Sodium nitroprusside (SNP) (2.5 mM) solution was used to determine the scavenging activities of these compounds. The levels of TNF-α in the culture medium were measured by using an ELISA kit. Semi-quantitative RT-PCR analysis was used to determine the mRNA levels of inducible NOS (iNOS) and TNF-α. Results It was found, for the first time, that certain resveratrol derivatives that have 3, 5-dimethoxyl groups in the A-ring, such as (E)-4- (3, 5-dimethoxystyryl) phenol (pterostilbene, compound 2), or have substituted the B-ring of resveratrol with quinolyl, such as (E)-5-[2-(quinolin-4-yl)vinyl] benzene-1, 3-diol (compound 18) and (E)-4-(3, 5-dimethoxystyryl)quinoline (compound 19), strongly inhibited NO production. Compounds 2, 18, and 19 reduced LPS-induced protein and mRNA expression of inducible NO synthase (iNOS), but did not display direct NO-scavenging activity up to 30 μM in sodium nitroprusside (SNP) solution. Moreover, compounds 2, 18, and 19 could also significantly inhibit the production of TNF-α by LPS-activated microglia. Furthermore, we found the demethoxy derivatives of eurcumin have more potent inhibition activity on NO and TNF-α releasing in activated-microglia. Conclusions In the present study we compared the activated-rnicroglia inhibition effect of resvertrol, curcumin and their derivatives and provided a glance of the structure-activity relationships of these compounds, the information is beneficial to design new potent compounds which can provide better therapeutic implications for various neurodegenerative diseases.

  15. Influência da maceração carbônica e da irradiação ultravioleta nos níveis de trans-resveratrol em vinhos de uva cabernet sauvignon Influence of the carbonic maceration on the levels of trans-resveratrol in cabernet sauvignon wine

    Directory of Open Access Journals (Sweden)

    Silvana Maria Michelin Bertagnolli

    2007-03-01

    Full Text Available O consumo moderado de vinho reduz significativamente os riscos de doenças cardiovasculares. Este efeito é atribuído aos polifenóis presentes no vinho, em especial ao resveratrol (3,5,4'-triidroxiestilbeno, que é uma fitoalexina encontrada em várias partes da videira, principalmente na casca da uva, assim como em outras espécies de plantas. Uvas da cultivar Cabernet Sauvignon foram submetidas à irradiação com luz ultravioleta e maceração carbônica e após fermentadas. Procedeu-se à coleta de amostras durante todo o experimento, as quais foram posteriormente analisadas quanto ao teor de trans-resveratrol através da Cromatografia Líquida de Alta Eficiência. Os resultados do trabalho demonstram que a evolução do conteúdo de trans-resveratrol foi ascendente durante as fases da fermentação. Diferenças ocorreram no final da fermentação, em que as amostras de vinhos com maceração carbônica apresentaram leve declínio, possivelmente pela atmosfera de CO2 na qual ficaram armazenadas, inibindo a formação do resveratrol. Ao final da fermentação principal a concentração de trans-resveratrol foi de 15 mg.L-1 em todos os tratamentos, chegando a 1,5 mg.L-1, em média, no final do período de estocagem.The moderate consumption of wine reduces the risks of heart diseases significantly. This effect is attributed to the polyphenols found in the wine, in special to resveratrol (3,5,4'-trihidroxistilbene that it is a phytoalexin found in the various parts of the vine, including in the skin of the grape, as well as in other species of plants. Grapes of cultivar Cabernet Sauvignon had been submitted to the irradiation with ultra-violet light and carbonic maceration and after fermented. It was proceeded all collection from samples during the experiment, which later had been analyzed how much to the concentration of trans-resveratrol using the Liquid Chromatography of High Efficiency. The of the content of trans-resveratrol was ascendent

  16. Resveratrol metabolites modify adipokine expression and secretion in 3T3-L1 pre-adipocytes and mature adipocytes.

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    Itziar Eseberri

    Full Text Available OBJECTIVE: Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue. METHODS: 3T3-L1 maturing pre-adipocytes were treated during differentiation with 25 µM of resveratrol or with its metabolites and 3T3-L1 mature adipocytes were treated for 24 hours with 10 µM resveratrol or its metabolites. The gene expression of adiponectin, leptin, visfatin and apelin was assessed by Real Time RT-PCR and their concentration in the incubation medium was quantified by ELISA. RESULTS: Resveratrol reduced mRNA levels of leptin and increased those of adiponectin. It induced the same changes in leptin secretion. Trans-resveratrol-3-O-glucuronide and trans-resveratrol-4'-O-glucuronide increased apelin and visfatin mRNA levels. Trans-resveratrol-3-O-sulfate reduced leptin mRNA levels and increased those of apelin and visfatin. CONCLUSIONS: The present study shows for the first time that resveratrol metabolites have a regulatory effect on adipokine expression and secretion. Since resveratrol has been reported to reduce body-fat accumulation and to improve insulin sensitivity, and considering that these effects are mediated in part by changes in the analyzed adipokines, it may be proposed that resveratrol metabolites play a part in these beneficial effects of resveratrol.

  17. Estrogen and Resveratrol Regulate Rac and Cdc42 Signaling to the Actin Cytoskeleton of Metastatic Breast Cancer Cells

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    Nicolas G. Azios

    2007-02-01

    Full Text Available Estrogen and structurally related molecules play critical roles in breast cancer. We reported that resveratrol (50 µM, an estrogen-like phytosterol from grapes, acts in an antiestrogenic manner in breast cancer cells to reduce cell migration and to induce a global and sustained extension of actin structures called filopodia. Herein, we report that resveratrol-induced filopodia formation is time-dependent and concentration-dependent. In contrast to resveratrol at 50 µM, resveratrol at 5 µM acts in a manner similar to estrogen by increasing lamellipodia, as well as cell migration and invasion. Because Rho GTPases regulate the extension of actin structures, we investigated a role for Rac and Cdc42 in estrogen and resveratrol signaling. Our results demonstrate that 50 µM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 µM resveratrol increase Rac activity in breast cancer cells. MDA-MB-231 cells expressing dominant-negative Cdc42 or dominantnegative Rac retain filopodia response to 50 µM resveratrol. Lamellipodia response to 5 µM resveratrol, estrogen, or epidermal growth factor is inhibited in cells expressing dominant-negative Rac, indicating that Rac regulates estrogen and resveratrol (5 µM signaling to the actin cytoskeleton. These results indicate that signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42.

  18. Increased resveratrol production in wines using engineered wine strains Saccharomyces cerevisiae EC1118 and relaxed antibiotic or auxotrophic selection.

    Science.gov (United States)

    Sun, Ping; Liang, Jing-Long; Kang, Lin-Zhi; Huang, Xiao-Yan; Huang, Jia-Jun; Ye, Zhi-Wei; Guo, Li-Qiong; Lin, Jun-Fang

    2015-01-01

    Resveratrol is a polyphenolic compound with diverse beneficial effects on human health. Red wine is the major dietary source of resveratrol but the amount that people can obtain from wines is limited. To increase the resveratrol production in wines, two expression vectors carrying 4-coumarate: coenzyme A ligase gene (4CL) from Arabidopsis thaliana and resveratrol synthase gene (RS) from Vitis vinifera were transformed into industrial wine strain Saccharomyces cerevisiae EC1118. When cultured with 1 mM p-coumaric acid, the engineered strains grown with and without the addition of antibiotics produced 8.249 and 3.317 mg/L of trans-resveratrol in the culture broth, respectively. Resveratrol content of the wine fermented with engineered strains was twice higher than that of the control, indicating that our engineered strains could increase the production of resveratrol during wine fermentation.

  19. 14C glucose uptake and turnover, a biomarker in benzo(a)pyrene induced lung carcinogenesis: role of curcumin and resveratrol

    International Nuclear Information System (INIS)

    Full text: The aim of the present study was to explore the synergistic potential of curcumin and resveratrol in modulation of glucose metabolism by studying 14C glucose uptake, turnover in the lung slices and ultra-histoarchitectural changes during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. The mice were segregated into five treatment groups which included group I (normal control), group II (BP treated), group III (BP+curcumin treated), group IV (BP+resveratrol treated) and group V (BP+curcumin+resveratrol treated). Animals in Group II were given a single intraperitoneal injection of Benzo(a)pyrene in corn oil at a dose level of 100mg/Kg body weight. Group III animals were given curcumin orally in drinking water at a dose level of 60 mg /Kg/ body weight, thrice a week. Animals in Group IV were given resveratrol orally at a dose level of 5.7 microgram/ml drinking water, thrice a week. Animals in group V were given a combined treatment of curcumin and resveratrol in a similar manner as was given to group III and group IV animals, respectively. All the animals had free access to the diet and water and the treatments continued for a total duration of 22 weeks. The morphological and ultra-histoachitectural analyses confirmed lung carcinogenesis, in the BP treated mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75 respectively in the BP treated mice. A statistically significant increase in the uptake of 14C glucose was observed in the lung slices of BP treated mice. Further, radiorespirometric analyses of 14C turnover also showed a significant increase in the lung slices of BP treated mice. The ultra-histoarchitecture of the BP treated mice revealed disruption in cellular integrity along with nuclear deformation. Mitochondria were swollen and cytoplasm appeared granular along with extensive vacuolization. Further, spaces between the endothelium, epithelium and basement membrane indicative of lung injury and edema were observed in

  20. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology

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    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S.; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  1. INTRAHIPPOCAMPAL ADMINISTRATION OF IBOTENIC ACID INDUCED CHOLINERGIC DYSFUNCTION via NR2A/NR2B EXPRESSION: IMPLICATIONS OF RESVERATROL AGAINST ALZHEIMER DISEASE PATHOPHYSIOLOGY

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    Chennakesavan eKarthick

    2016-04-01

    Full Text Available Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression towards Alzheimer’s disease (AD pathology. Resveratrol (RSV, a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5µg/µl lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20mg/kg body weight, i.p significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the

  2. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

    Science.gov (United States)

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  3. Riboflavin Phototransformation on the Changes of Antioxidant Capacities in Phenolic Compounds.

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    Song, Juhee; Seol, Nam Gyu; Kim, Mi-Ja; Lee, JaeHwan

    2016-08-01

    Eight phenolic compounds including: p-coumaric acid, vanillic acid, caffeic acid, chlorogenic acid, trolox, quercetin, curcumin, and resveratrol were treated with riboflavin (RF) photosensitization and in vitro antioxidant capacities of the mixtures were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2' azino bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Mixtures containing p-coumaric acid and vanillic acid under RF photosensitization showed increases in ferric ion reducing ability and radical scavenging activity of DPPH, whereas mixtures of other compounds had decreases in both radical scavenging ability and ferric reducing antioxidant power. Hydroxycoumaric acid and conjugated hydroxycoumaric and coumaric acids were tentatively identified from RF photosensitized p-coumaric acid, whereas dimmers of vanillic acid were tentatively identified from RF photosensitized vanillic acid. RF photosensitization may be a useful method to enhance antioxidant properties like ferric ion reducing abilities of some selected phenolic compounds. PMID:27387389

  4. Riboflavin Phototransformation on the Changes of Antioxidant Capacities in Phenolic Compounds.

    Science.gov (United States)

    Song, Juhee; Seol, Nam Gyu; Kim, Mi-Ja; Lee, JaeHwan

    2016-08-01

    Eight phenolic compounds including: p-coumaric acid, vanillic acid, caffeic acid, chlorogenic acid, trolox, quercetin, curcumin, and resveratrol were treated with riboflavin (RF) photosensitization and in vitro antioxidant capacities of the mixtures were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2' azino bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Mixtures containing p-coumaric acid and vanillic acid under RF photosensitization showed increases in ferric ion reducing ability and radical scavenging activity of DPPH, whereas mixtures of other compounds had decreases in both radical scavenging ability and ferric reducing antioxidant power. Hydroxycoumaric acid and conjugated hydroxycoumaric and coumaric acids were tentatively identified from RF photosensitized p-coumaric acid, whereas dimmers of vanillic acid were tentatively identified from RF photosensitized vanillic acid. RF photosensitization may be a useful method to enhance antioxidant properties like ferric ion reducing abilities of some selected phenolic compounds.

  5. Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer

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    Anthony V Nguyen

    2009-04-01

    Full Text Available Anthony V Nguyen1, Micaela Martinez1, Michael J Stamos2, Mary P Moyer3, Kestutis Planutis1, Christopher Hope1 Randall F Holcombe11Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, 2Department of Surgery, University of California, Irvine CA, USA; 3Incell Corporation, San Antonio, TX USAContext: Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro.Design: A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR pre- and post-exposure to resveratrol/GP.Results: Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03 activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001. These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line.Conclusions: These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted.Trial registration: NCT00256334

  6. Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy

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    Naini Bhadri

    2013-01-01

    Full Text Available Cisplatin or cis-diamminedichloroplatinum (II (CDDP is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA, and coenzyme Q10 (CoQ10, in cisplatin (2 mg/kg i.p. twice weekly induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po with resveratrol (10 mg/kg/day i.p. or ALA (20 mg/kg/day i.p. or CoQ10 (10 mg/kg weekly thrice i.p. exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.

  7. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice.

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    Jeong, Sae Im; Shin, Jin A; Cho, Sunghee; Kim, Hye Won; Lee, Ji Yoon; Kang, Jihee Lee; Park, Eun-Mi

    2016-08-01

    Resveratrol is known to improve metabolic dysfunction associated with obesity. Visceral obesity is a sign of aging and is considered a risk factor for ischemic stroke. In this study, we investigated the effects of resveratrol on inflammation in visceral adipose tissue and the brain and its effects on ischemic brain injury in aged female mice. Mice treated with resveratrol (0.1 mg/kg, p.o.) for 10 days showed reduced levels of interleukin-1β and tumor necrosis factor-α, as well as a reduction in the size of adipocytes in visceral adipose tissue. Resveratrol also reduced interleukin-1β and tumor necrosis factor-α protein levels and immunoglobulin G extravasation in the brain. Mice treated with resveratrol demonstrated smaller infarct size, improved neurological function, and blunted peripheral inflammation at 3 days postischemic stroke. These results showed that resveratrol counteracted inflammation in visceral adipose tissue and in the brain and reduced stroke-induced brain injury and peripheral inflammation in aged female mice. Therefore, resveratrol administration can be a valuable strategy for the prevention of age-associated and disease-provoked inflammation in postmenopausal women. PMID:27318135

  8. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

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    Stéphanie Rimbaud

    Full Text Available Heart failure (HF is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polypheno