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Sample records for antioxidant resveratrol significantly

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Antioxidant and anti-inflammatory effects of resveratrol in airway disease.

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    Wood, Lisa G; Wark, Peter A B; Garg, Manohar L

    2010-11-15

    Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are a significant and increasing global health problem. These diseases are characterized by airway inflammation, which develops in response to various stimuli. In asthma, inflammation is driven by exposure to a variety of triggers, including allergens and viruses, which activate components of both the innate and acquired immune responses. In COPD, exposure to cigarette smoke is the primary stimulus of airway inflammation. Activation of airway inflammatory cells leads to the release of excessive quantities of reactive oxygen species (ROS), resulting in oxidative stress. Antioxidants provide protection against the damaging effects of oxidative stress and thus may be useful in the management of inflammatory airways disease. Resveratrol, a polyphenol that demonstrates both antioxidative and anti-inflammatory functions, has been shown to improve outcomes in a variety of diseases, in particular, in cancer. We review the evidence for a protective role of resveratrol in respiratory disease. Mechanisms of resveratrol action that may be relevant to respiratory disease are described. We conclude that resveratrol has potential as a therapeutic agent in respiratory disease, which should be further investigated. PMID:20214495

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Resveratrol

    Czech Academy of Sciences Publication Activity Database

    Šmidrkal, J.; Filip, V.; Prekop, J.; Kolouchová, I.; Melzoch, K.; Harmatha, Juraj

    Pardubice: Univerzita Pardubice, 2004, s. 243-248. ISBN 80-7194-644-3. [Vitamins 2004, Targeted Nutritional Therapy. Pardubice (CZ), 13.09.2004-15.09.2004] Institutional research plan: CEZ:AV0Z4055905 Keywords : resveratrol * pterostilben * pinosylvin Subject RIV: CC - Organic Chemistry

  11. Revised structure of trans-resveratrol: Implications for its proposed antioxidant mechanism.

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    Zarychta, Bartosz; Gianopoulos, Christopher G; Pinkerton, A Alan

    2016-03-01

    The crystal structure of trans-resveratrol has been redetermined by X-ray diffraction. The newly refined structure demonstrates that the previously reported, dynamically disordered hydrogen-bonding network is rather the superposition of two crystallographically independent molecules of trans-resveratrol. This latter arrangement possesses a well-defined hydrogen-bonding network in a unit cell of double the previously reported volume. While not meant as a criticism of the proposed antioxidant mechanism itself, the present studies clearly show that the X-ray diffraction data should no longer be used for its additional support. PMID:26856924

  12. Evaluation of efficacy and tolerance of a nighttime topical antioxidant containing resveratrol, baicalin, and vitamin e for treatment of mild to moderately photodamaged skin.

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    Farris, Patricia; Yatskayer, Margarita; Chen, Nannan; Krol, Yevgeniy; Oresajo, Christian

    2014-12-01

    Resveratrol is an effective anti-aging molecule with diverse biologic activity. It functions as a dual antioxidant that can neutralize free radicals and increase intrinsic antioxidant capacity. Additionally resveratrol increases mitochondrial biogenesis and has anti-inflammatory, anti-diabetic, and anti-cancer activity. In this paper we will focus on the use of topically applied resveratrol using a proprietary blend containing 1% resveratrol, 0.5% baicalin, and 1% vitamin E. This stabilized high concentration formulation demonstrates percutaneous absorption and alterations in gene expression such as hemoxygenase-1 (HO-1), vascular endothelial growth factor (VEGFA), and collagen 3 (COL3A1). Clinical assessment showed a statistically significant improvement in fine lines and wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation, radiance, and skin roughness over baseline in 12 weeks. Ultrasound measurements in the periorbital area showed an average improvement of 18.9% in dermal thickness suggesting significant dermal remodeling. These studies confirm that topical resveratrol, baicalin, and vitamin E are valuable ingredient that can be used for skin rejuvenation. PMID:25607790

  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.

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    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. 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.

  16. 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

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

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    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. PMID:18420333

  18. 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

  19. 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.

  20. Resveratrol and liver: A systematic review

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    Forouzan Faghihzadeh

    2015-01-01

    Full Text Available Background: Recent studies demonstrated that resveratrol has many therapeutic effects on liver disorders. Resveratrol significantly increased survival after liver transplantation, decreased fat deposition, necrosis, and apoptosis which induced by ischemia in Wistar rats. It provided liver protection against chemical, cholestatic, and alcohol injury. Resveratrol can improve glucose metabolism and lipid profile and decrease liver fibrosis and steatosis. Furthermore, it was able to alter hepatic cell fatty acid composition. According to extension of liver disease around the world and necessity of finding new threat, this review critically examines the current preclinical in vitro and in vivo studies on the preventive and therapeutic effects of resveratrol in liver disorders. Materials and Methods: A search in PubMed, Google Scholar, and Scopus was undertaken to identify relevant literature using search terms, including "liver," "hepatic," and "Resveratrol." Both in vivo and in vitro studies were included. No time limiting considered for this search. Results: A total of 76 articles were eligible for this review. In these articles, resveratrol shows antioxidative properties in different models of hepatitis resulting in reducing of hepatic fibrosis. Conclusion: Resveratrol could reduce hepatic steatosis through modulating the insulin resistance and lipid profile in animals. These high quality preclinical studies propose the potential therapeutic implication of resveratrol in liver disorders especially those with hepatic steatosis. Resveratrol can play a pivotal role in prevention and treatment of liver disorders by reducing hepatic fibrosis.

  1. 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.

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

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    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

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

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    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

  4. 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.

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

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    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

  6. Ovarian actions of resveratrol.

    Science.gov (United States)

    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

  7. Resveratrol as a Potential Therapeutic Candidate for the Treatment and Management of Alzheimer's Disease.

    Science.gov (United States)

    Braidy, Nady; Jugder, Bat-Erdene; Poljak, Anne; Jayasena, Tharusha; Mansour, Hussein; Nabavi, Seyed Mohammad; Sachdev, Perminder; Grant, Ross

    2016-01-01

    Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical present in red wine, grapes, berries, chocolate and peanuts. Clinically, resveratrol has exhibited significant antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties. Although resveratrol was first isolated in 1940, it was not until the last decade that it was recognised for its potential therapeutic role in reducing the risk of neurodegeneration, and Alzheimer's disease (AD) in particular. AD is the primary cause of progressive dementia. Resveratrol has demonstrated neuroprotective effects in several in vitro and in vivo models of AD. Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that resveratrol also facilitates non-amyloidogenic breakdown of the amyloid precursor protein (APP), and promotes removal of neurotoxic amyloid beta (Aβ) peptides, a critical step in preventing and slowing down AD pathology. Resveratrol also reduces damage to neuronal cells via a variety of additional mechanisms, most notably is the activation of NAD(+)-dependent histone deacetylases enzymes, termed sirtuins. However in spite of the considerable advances in clarifying the mechanism of action of resveratrol, it is unlikely to be effective as monotherapy in AD due to its poor bioavailability, biotransformation, and requisite synergism with other dietary factors. This review summarizes the relevance of resveratrol in the pathophysiology of AD. It also highlights why resveratrol alone may not be an effective single therapy, and how resveratrol coupled to other compounds might yet prove an effective therapy with multiple targets. PMID:26845555

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Resveratrol, sirtuins, and viruses.

    Science.gov (United States)

    Yang, Tao; Li, Shugang; Zhang, Xuming; Pang, Xiaowu; Lin, Qinlu; Cao, Jianzhong

    2015-11-01

    Resveratrol is a natural phenolic product found in some plants in response to stress and has been linked to the many health benefits of red wine. Over the past several decades, a great deal of research has identified diverse biological roles associated with resveratrol, including anti-oxidant, anti-proliferation, anti-inflammation, anti-cancer, anti-fungal, and antiviral activities. Such biological activities of resveratrol are likely mediated through multiple cellular targets or pathways, such as sirtuins, a family of NAD(+)-dependent deacetylases. In this treatise, the literatures focusing on the roles of resveratrol and sirtuins in modulating infections by a broad-spectrum of viruses are reviewed, with an emphasis on its potential antiviral mechanisms. A working model about the effects of resveratrol on virus infection is proposed to stimulate further researches on this exciting topic. PMID:26479742

  10. Significance of antioxidants in experimental hypertension

    Czech Academy of Sciences Publication Activity Database

    Pecháňová, Olga; Zicha, Josef; Kojšová, S.; Jendeková, L.; Sládková, M.; Paulis, L.; Janega, P.; Csizmadiová, Z.; Bernátová, I.; Dobešová, Zdenka; Šimko, F.; Babál, P.; Andriantsitohaina, R.; Kuneš, Jaroslav

    Fyziologický ústav AV ČR, v. v. i.. Roč. 55, č. 3 (2006), 3P-4P ISSN 0862-8408. [Nitric Oxide: Basic Regulations and Pharmacological Interventions. 21.09.2005-24.09.2005, Tucepi] Grant ostatní: VEGA(SK) 2/6148/26; VEGA(SK) 1/3429/06; APVT(SK) 51-027404 Keywords : antioxidants * experimental hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

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

    Directory of Open Access Journals (Sweden)

    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. Distribution and Antioxidant Efficiency of Resveratrol in Stripped Corn Oil Emulsions

    OpenAIRE

    Sonia Losada-Barreiro; Marlene Costa; Carlos Bravo-Díaz; Fátima Paiva-Martins

    2014-01-01

    We investigated the effects of resveratrol (RES) on the oxidative stability of emulsions composed of stripped corn oil, acidic water and Tween 20 and determined its distribution in the intact emulsions by employing a well-established kinetic method. The distribution of RES is described by two partition constants, that between the oil-interfacial region, P O I, and that between the aqueous and interfacial region, P W I. The partition constants, P O I and P W I, are obtained in the intact emuls...

  13. Resveratrol and Health

    DEFF Research Database (Denmark)

    This volume examines the phytoalexin resveratrol and the ongoing studies about its effects on lifespan and health. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi, significantly extends the...... lifespan of the yeast Saccharomyces cerevisiae, Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Resveratrol is currently a topic of numerous animal and human studies into its effects. The effects of resveratrol on the lifespan of many model organisms remain controversial. Anti...

  14. Distribution and Antioxidant Efficiency of Resveratrol in Stripped Corn Oil Emulsions

    Directory of Open Access Journals (Sweden)

    Sonia Losada-Barreiro

    2014-04-01

    Full Text Available We investigated the effects of resveratrol (RES on the oxidative stability of emulsions composed of stripped corn oil, acidic water and Tween 20 and determined its distribution in the intact emulsions by employing a well-established kinetic method. The distribution of RES is described by two partition constants, that between the oil-interfacial region, POI, and that between the aqueous and interfacial region, PWI. The partition constants, POI and PWI, are obtained in the intact emulsions from the variations of the observed rate constant, kobs, for the reaction between the hydrophobic 4-hexadecylbenzenediazonium ion and RES with the emulsifier volume fraction, ФI. The obtained POI and PWI values are quite high, PWI = 4374 and POI = 930, indicating that RES is primarily located in the interfacial region of the emulsions, %RESI > 90% at ФI = 0.005, increasing up to 99% at ФI = 0.04. The oxidative stability of the corn oil emulsions was determined by measuring the formation of conjugated dienes at a given time in the absence and in the presence of RES. The addition of RES did not improve their oxidative stability in spite that more than 90% of RES is located in the interfacial region of the emulsion, because of the very low radical scavenging activity of RES.

  15. 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

  16. 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

  17. Resveratrol and Myopathy

    Science.gov (United States)

    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

  18. Resveratrol and Myopathy.

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  1. Resveratrol and its biological actions

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. 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

  4. Protective effects of resveratrol in experimental retinal detachment.

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. Resveratrol and Ophthalmic Diseases.

    Science.gov (United States)

    Abu-Amero, Khaled K; Kondkar, Altaf A; Chalam, Kakarla V

    2016-01-01

    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. PMID:27058553

  8. 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

  9. 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

  10. Anticancer Molecular Mechanisms of Resveratrol

    Science.gov (United States)

    Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

    2016-01-01

    Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

  11. Synthesis and study of new paramagnetic resveratrol analogues.

    Science.gov (United States)

    Kálai, Tamás; Borza, Erzsébet; Antus, Csenge; Radnai, Balázs; Gulyás-Fekete, Gergely; Fehér, Andrea; Sümegi, Balázs; Hideg, Kálmán

    2011-12-15

    New resveratrol analogues containing five- and six-membered nitroxides and isoindoline nitroxides were synthesized. These new compounds were compared to resveratrol based on their ABTS radical scavenging ability as well on their capacity to suppress inflammatory process in macrophages induced by lipopolysaccharides. The ABTS and ROS scavenging activities of new molecules were the same or weaker than that of resveratrol, but some of paramagnetic resveratrol derivatives suppressed nitrite and TNFα production more efficiently than resveratrol. Based on these results the new nitroxide and phenol containing hybrid molecules can be considered as new antioxidant and anti-inflammatory agents. PMID:22088309

  12. 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)

  13. Inhibition of swarming and virulence factor expression in Proteus mirabilis by resveratrol.

    Science.gov (United States)

    Wang, Won-Bo; Lai, Hsin-Chih; Hsueh, Po-Ren; Chiou, Robin Y-Y; Lin, Shwu-Bin; Liaw, Shwu-Jen

    2006-10-01

    Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a phytoalexin compound with anti-inflammatory and antioxidant activities. The effect of resveratrol on swarming and virulence factor expression of Proteus mirabilis, an important pathogen infecting the urinary tract, was determined on swarming agar plates with and without the compound. Bacteria harvested at different times were assayed for cell length and the production of flagella, haemolysin and urease. Resveratrol inhibited P. mirabilis swarming and virulence factor expression in a dose-dependent manner. Resveratrol significantly inhibited swarming at 15 microg ml(-1), and completely inhibited swarming at 60 microg ml(-1). Inhibition of swarming and virulence factor expression was mediated through RsbA, a His-containing phosphotransmitter of the bacterial two-component signalling system possibly involved in quorum sensing. Complementation of an rsbA-defective mutant with the rsbA gene restored its responsiveness to resveratrol. The compound also inhibited the ability of P. mirabilis to invade human urothelial cells. These findings suggest that resveratrol has potential to be developed as an antimicrobial agent against P. mirabilis infection. PMID:17005777

  14. 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

  15. 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

  16. Resveratrol and Cardiovascular Diseases

    OpenAIRE

    Dominique Bonnefont-Rousselot

    2016-01-01

    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 peroxi...

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Ana Rute Neves

    2016-03-01

    Full Text Available 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.

  19. 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)

  20. 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.

  1. 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.

  2. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty.

    Science.gov (United States)

    Mendes, Talita Biude; Paccola, Camila Cicconi; de Oliveira Neves, Flávia Macedo; Simas, Joana Noguères; da Costa Vaz, André; Cabral, Regina Elisabeth L; Vendramini, Vanessa; Miraglia, Sandra Maria

    2016-07-01

    The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood. PMID:27069006

  3. 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.

  4. Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice.

    Science.gov (United States)

    Ge, Li; Liu, Liwei; Liu, Hansen; Liu, Song; Xue, Hao; Wang, Xueer; Yuan, Lin; Wang, Zhen; Liu, Dexiang

    2015-12-01

    Current evidence supports that depression is accompanied by the activation of the inflammatory-response system, and overproduction of pro-inflammatory cytokines may play a role in the pathophysiology of depressive disorders. Resveratrol has anti-inflammatory, antioxidant and anti-depressant-like properties. Using an animal model of depression induced by a single administration of lipopolysaccharide (LPS), the present study investigated the effects of resveratrol on LPS-induced depressive-like behavior and inflammatory-response in adult mice. Our results showed that pretreatment with resveratrol (80mg/kg, i.p.) for 7 consecutive days reversed LPS-increased the immobility time in the forced swimming test and tail suspension test, and LPS-reduced sucrose preference test. Moreover, the antidepressant action of resveratrol was paralleled by significantly reducing the expression levels of pro-inflammatory cytokines, and up-regulating phosphorylated cAMP response-element-binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) expression in prefrontal cortex (PFC) and hippocampus. In addition, resveratrol ameliorated LPS-induced NF-κB activation in the PFC and hippocampus. The results demonstrate that resveratrol may be an effective therapeutic agent for LPS-induced depressive-like behavior, partially due to its anti-inflammatory aptitude and by modulating pCREB and BDNF expression in the brain region of mice. PMID:26485503

  5. PHYSIOLOGICAL EFFECTS OF RESVERATROL AND COUMARIC ACID ON TWO MAJOR GROUNDNUT PESTS AND THEIR EGG PARASITOID BEHAVIOR.

    Science.gov (United States)

    Sambangi, Pratyusha; Rani, Pathipati Usha

    2016-04-01

    Groundnut, Arachis hypogea L., is one of the plant species that synthesizes phenolic compounds, resveratrol and coumaric acid. They are induced as a defense strategy in plant in response to feeding lepidopterans. The present study investigated the role of resveratrol and coumaric acid in producing antiherbivore effects as a direct defense against two major groundnut pests, Spodoptera litura F. and Amsacta albistriga W., and in indirect defense by attracting the egg parasitoid Trichogramma chilonis Ishii under laboratory conditions. The phenolic compounds deterred the feeding of both pests and caused reduction in the larval weights in a dose-dependent manner in leaf disk bioassays. Antioxidant mechanisms of larvae fed with these phenols were measured by estimating the activities of superoxide dismutase (SOD), ascorbate peroxidase (APOX), and catalase (CAT). Enzyme activities increased significantly in experimental larvae, more so in resveratrol-treated than in coumaric acid treated larvae. Feeding larvae with resveratrol and coumaric acid resulted in enhanced activities of detoxifying enzymes, carboxyl esterase (EST), and glutathione-S-transferase (GST) in the midgut tissues of both species, indicating the toxic nature of these compounds. Trichogramma chilonis was more attracted toward coumaric acid treatments in Y-olfactometer tests than to resveratrol. This study contributes to the understanding of the roles of resveratrol and coumaric acid in direct as well as indirect defense, we infer a possible utilization of these compounds in alternate measures of groundnut pest control in future. PMID:26890503

  6. 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)

  7. 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)

  8. 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)

  9. Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Xiaolin Zhang

    2015-11-01

    Full Text Available Helicobacter pylori (H. pylori-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect. The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice. A mouse model of H. pylori infection was established via oral inoculation with H. pylori. After one week, mice were administered resveratrol (100 mg/kg body weight/day orally for six weeks. The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA. The expression levels of IκBα and phosphorylated IκBα (which embodies the level and activation of NF-κB, Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme and nuclear factor-erythroid 2 related factor 2 (Nrf2 were determined using Western blot, and lipid peroxide (LPO level and myeloperoxidase (MPO activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa. The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa. Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of IκBα, and increased the levels of HO-1 and Nrf2. In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-κB, and moreover through the activation of the Nrf2/HO-1 pathway.

  10. Cypermethrin-induced reproductive toxicity in the rat is prevented by resveratrol

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    Poonam Sharma

    2014-01-01

    Full Text Available Aims : The current study was to assess the protective role of resveratrol in cypermethrin-induced reproductive toxicity in male Wistar rats. Materials and Methods : Rats were exposed to cypermethrin (3.83 mg/kg bw for 14 days. Pre- and post-treatment of resveratrol (20 mg/kg bw for 14 days was given to cypermethrin exposed rats. At the end of the experiment, rats were sacrificed, testis and epididymis were removed, sperm characteristics, sex hormones, and various biochemical parameters were studied. Results : Cypermethrin exposure resulted in a significant decrease in weight of testis and epididymis, testicular sperm head counts, sperm motility and live sperm counts and increase in sperm abnormalities. Serum testosterone (T, follicle stimulating hormone (FSH, luteinizing hormone (LH, reduced glutathione (GSH, catalase (CAT, superoxide dismutase (SOD, glutathione S-transferase (GST, glutathione reductase (GR, glutathione peroxidase (GPx and total protein (TP content were decreased and lipid peroxidation (LPO level was increased on cypermethrin exposure. Pre- and post-treatment of resveratrol increased sperm head counts, sperm motility, live sperm counts, T, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and TP contents and decreased LPO. Treatment with resveratrol alone has improved sperm parameters and testicular antioxidant defence system. Conclusion : The study concluded that resveratrol ameliorated cypermethrin-induced testicular damage by reducing oxidative stress and by enhancing the level of sex hormones.

  11. 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...

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

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    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

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

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    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.

  14. Triple antioxidant SNEDDS formulation with enhanced oral bioavailability

    DEFF Research Database (Denmark)

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

    2016-01-01

    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......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 ... 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....

  15. Resveratrol: A Potential Hippocampal Plasticity Enhancer

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    Gisele Pereira Dias

    2016-01-01

    Full Text Available The search for molecules capable of restoring altered hippocampal plasticity in psychiatric and neurological conditions is one of the most important tasks of modern neuroscience. It is well established that neural plasticity, such as the ability of the postnatal hippocampus to continuously generate newly functional neurons throughout life, a process called adult hippocampal neurogenesis (AHN, can be modulated not only by pharmacological agents, physical exercise, and environmental enrichment, but also by “nutraceutical” agents. In this review we focus on resveratrol, a phenol and phytoalexin found in the skin of grapes and red berries, as well as in nuts. Resveratrol has been reported to have antioxidant and antitumor properties, but its effects as a neural plasticity inducer are still debated. The current review examines recent evidence implicating resveratrol in regulating hippocampal neural plasticity and in mitigating the effects of various disorders and diseases on this important brain structure. Overall, findings show that resveratrol can improve cognition and mood and enhance hippocampal plasticity and AHN; however, some studies report opposite effects, with resveratrol inhibiting aspects of AHN. Therefore, further investigation is needed to resolve these controversies before resveratrol can be established as a safe coadjuvant in preventing and treating neuropsychiatric conditions.

  16. Resveratrol prevents ammonia toxicity in astroglial cells.

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    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.

  17. 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

  18. 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

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

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    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.

  20. Resveratrol and derivatives for the treatment of atrial fibrillation.

    Science.gov (United States)

    Baczkó, István; Light, Peter E

    2015-08-01

    Resveratrol is a bioactive polyphenol, found in grapes, red wine, and peanuts, and has recently garnered much media and scientific attention for its diverse beneficial health effects as a nutritional supplement or nutraceutical. Of particular interest are the well-documented cardioprotective effects of resveratrol that are mediated by diverse mechanisms, including its antioxidant and vascular effects. However, it is now becoming clear that resveratrol may also exhibit direct effects on cardiac function and rhythm through modulation of signaling pathways that regulate cardiac remodeling and ion channel activity that controls cardiac excitability. Resveratrol may therefore possess antiarrhythmic properties that contribute to the cardiovascular benefits of resveratrol. Atrial fibrillation (AF) is the most common cardiac arrhythmia, although current therapies are suboptimal. Our laboratory has been studying resveratrol's effects on cardiac ion channels and remodeling pathways, and we initiated a drug development program aimed at generating novel resveratrol derivatives with improved efficacy against AF when compared to currently available therapeutics. This review therefore focuses on the effects of resveratrol and new derivatives on a variety of cardiac ion channels and molecular pathways that contribute to the development and maintenance of atrial fibrillation. PMID:26205342

  1. [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

  2. 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.

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

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    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

  4. 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.

  5. Flavonoids as Antioxidants and Developmental Regulators: Relative Significance in Plants and Humans

    OpenAIRE

    Massimiliano Tattini; Susanna Pollastri; Alessio Fini; Cecilia Brunetti; Martina Di Ferdinando

    2013-01-01

    Phenylpropanoids, particularly flavonoids have been recently suggested as playing primary antioxidant functions in the responses of plants to a wide range of abiotic stresses. Furthermore, flavonoids are effective endogenous regulators of auxin movement, thus behaving as developmental regulators. Flavonoids are capable of controlling the development of individual organs and the whole-plant; and, hence, to contribute to stress-induced morphogenic responses of plants. The significance of flavon...

  6. 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.

  7. 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.

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

    International Nuclear Information System (INIS)

    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)

  9. 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)

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

    Science.gov (United States)

    Arteaga, Olatz; Revuelta, Miren; Urigüen, Leyre; Álvarez, Antonia; Montalvo, Haizea; Hilario, Enrique

    2015-01-01

    Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia. PMID:26544861

  16. Resveratrol exerts no effect on inflammatory response and delayed onset muscle soreness after a marathon in male athletes.

    OpenAIRE

    Laupheimer, M W; Perry, M; Benton, S.; Malliaras, P; Maffulli, N.

    2014-01-01

    Objective We investigated whether the inflammatory response and delayed onset of muscle soreness after a marathon are altered by resveratrol, a natural polyphenolic flavonoid antioxidant. Design: Double blind placebo-controlled randomised pilot study. Setting: London Marathon. Participants: Marathon race participants Interventions: 7 healthy male athletes were randomised to receive Resveratrol (600 mg Resveratrol daily for 7 days immediately before the marathon) or a placebo. Main Outcome Mea...

  17. Antioxidants

    Science.gov (United States)

    ... prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and vegetables. They are also available ... t clear whether this is because of the antioxidants, something else in the foods, or other factors. High-dose supplements of antioxidants ...

  18. 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

  19. Effect of stilbene resveratrol on haematological indices of rats

    Czech Academy of Sciences Publication Activity Database

    Doubek, J.; Volný, T.; Lojek, Antonín; Knotková, Z.; Kotrbáček, V.; Scheer, P.; Holešovská, Z.

    2005-01-01

    Roč. 74, č. 2 (2005), s. 205-208. ISSN 0001-7213 Institutional research plan: CEZ:AV0Z50040507 Keywords : antioxidative capacity * stilbene-resveratrol Subject RIV: BO - Biophysics Impact factor: 0.353, year: 2005

  20. 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.

  1. Modulation of TRP channels by resveratrol and other stilbenoids

    Directory of Open Access Journals (Sweden)

    Yu Lina

    2013-02-01

    Full Text Available Abstract Background Resveratrol (3,5,4’ - trihydroxy-trans-stilbene, a widely distributed natural stilbenoid, was proposed to account for the unique effects of red wine on life span and health. It has been reported to possess various biological and pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-carcinogenic effects. Here, using whole-cell patch-clamp techniques and behavioral analyses, we investigated whether resveratrol and other stilbenoids can modulate TRP channels in sensory neurons in vitro, and have analgesic effects in vivo. Results We found that resveratrol dose-dependently suppressed the allyl isothiocyanate (AITC-induced currents (IAITC in HEK293 cells that express TRPA1, as well as in rat dorsal root ganglion (DRG neurons. Instead, pinosylvin methyl ether (PME, another derivate of stilbene which has a similar structure to resveratrol, dose-dependently blocked the capsaicin-induced currents (ICAP in HEK293 cells that express TRPV1 as well as in DRG neurons. Interestingly, resveratrol had no inhibitory effect on the ICAP, and PME had no effect on the IAITC. Otherwise, trans-stilbene showed no any effect on IAITC or ICAP. The concentration response curve of AITC showed that resveratrol inhibited the action of TRPA1 not by changing the EC50, but by suppressing the AITC-induced maximum response. By contrast, the inhibition of TRPV1 by PME did not change the capsaicin-induced maximum response but did cause a right shift of the EC50. Moreover, pre-administration of resveratrol suppressed intraplantar injections of AITC-evoked nocifensive behaviors, as well as that PME suppressed capsaicin-evoked one. Conclusions These data suggest that resveratrol and other stilbenoids may have an inhibitory effect on TRP channels. In addition, these stilbenoids modulate TRP channel activity in different ways.

  2. 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

  3. 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

  4. Suppressive Effects of Resveratrol Treatment on The Intrinsic Evoked Excitability of CA1 Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Gholamhossein Meftahi

    2015-10-01

    Full Text Available Objective: Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neuronal function, little effort, if any, has been made to investigate the cellular effect of resveratrol treatment on intrinsic neuronal properties. Materials and Methods: This experimental study was performed to examine the acute effects of resveratrol (100 μM on the intrinsic evoked responses of rat Cornu Ammonis (CA1 pyramidal neurons in brain slices, using whole cell patch clamp recording under current clamp conditions. Results: Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05 increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol. Conclusion: Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity.

  5. A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages.

    Science.gov (United States)

    Duan, Wen-Jun; Li, Yi-Fang; Liu, Fang-Lan; Deng, Jie; Wu, Yan-Ping; Yuan, Wei-Lin; Tsoi, Bun; Chen, Jun-Li; Wang, Qi; Cai, Shao-Hui; Kurihara, Hiroshi; He, Rong-Rong

    2016-06-01

    Resveratrol gains a great interest for its strong antioxidant properties, while the molecular mechanisms underlie the beneficial effects on psychosocial stress remain controversial. In this study, we demonstrated that resveratrol protected peritoneal macrophages and RAW 264.7 cells from stress-induced decrease in the total cell count, phagocytic capability, reactive oxygen species generation, monodansylcadaverine and mitochondrial membrane potential in stressed mice. Resveratrol promoted stress-induced autophagy in both models. Modulation of autophagy by rapamycin or 3-methyladenine regulated the protective effect of resveratrol, suggesting a role of autophagy in the protective mechanisms of resveratrol. The comparison studies revealed that distinct mechanisms were implicated in the protective effect of resveratrol and other antioxidants (vitamin C and edaravone). Resveratrol promoted autophagy via upregulating SIRT3 expression and phosphorylation of AMP-activated protein kinase (AMPK). Knockdown of SIRT3 resulted in decreased autophagy and abolished protective effect of resveratrol. SIRT1 was also involved in the protective mechanism of resveratrol, although its effect on autophagy was unnoticeable. Pharmacological manipulation of autophagy modulated the effects of resveratrol on SIRT3 and AMPK, revealing the engagement of a positive feedback loop. In sharp contrast, vitamin C and edaravone effectively protected macrophages from stress-induced cytotoxicity, accompanied by downregulated SIRT3 expression and AMPK phosphorylation, and decreased level of autophagy response. Taken together, we conclude that a SIRT3/AMPK/autophagy network orchestrates in the protective effect of resveratrol in macrophages. PMID:27021965

  6. Resveratrol food supplements

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-01-01

    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 resveratrol supplements. Methods: A survey sent to a representative online panel in the United States and Denmark was analysed using linear regression. Results: We find that sociodemographic variables contribute little to explaining favourable attitudes toward and adoption intentions of...... intention. An interest in the indulgence dimension of food explains positive attitudes in the United States and adoption intentions in both countries. Conclusions: The results indicate that potential consumers of resveratrol supplements are identified by their usage of complementary and alternative medicine...

  7. 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...

  8. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men

    DEFF Research Database (Denmark)

    Hybholt, Lasse Gliemann; Schmidt, Jakob Friis; Olesen, Jesper;

    2013-01-01

    signaling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; BMI: 25.4 ± 0.7 kg/m2; MAP: 95.8 ± 2.......02) and muscle TBX synthase was higher in the resveratrol group after training (P <0.05). Resveratrol administration also abolished the positive effects of exercise on LDL, TC/HDL ratio and triglycerides concentrations in blood (P <0.05). Resveratrol did not potentiate the effect of exercise training on......Aging is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which, in animal studies has been shown to decrease atherosclerosis, improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1...

  9. Resveratrol Fails to Extend Life Span in the Mosquito Anopheles stephensi.

    Science.gov (United States)

    Johnson, Adiv A; Riehle, Michael A

    2015-10-01

    Resveratrol, a plant polyphenol present in grape skins, has been theorized to account for the "French Paradox" by explaining how red wine may decrease the health risks associated with unhealthy diets. Resveratrol has been reported to extend life span in several different species. Other studies, however, have failed to find a resveratrol-induced life span effect. A recent meta-study analyzing previously published survival data concluded that, although resveratrol reliably and reproducibly extends life span in some species, its life span effects show diminished reliability in other organisms. The data are mixed, and it remains unclear how evolutionarily conserved resveratrol's effects on life span are. To gain further insight into this controversy, we studied the effects of various concentrations (200 μM, 100 μM, 50 μM, or 0 μM) of orally fed resveratrol on the life span of the mosquito Anopheles stephensi, an important vector of human malaria, under two different feeding treatments--sugar-fed only or sugar-fed with intermittent blood meals. Each treatment was repeated three times and both survivorship and mortality rates were analyzed for each replicate. For the majority of experiments, resveratrol failed to mediate a statistically significant effect on life span. Although there was one instance where resveratrol significantly increased life span, there were five other instances where resveratrol significantly decreased life span. We conclude from these data that, under normal conditions, resveratrol does not extend life span in A. stephensi. PMID:25848933

  10. 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...

  11. 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.

  12. 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.

  13. Resveratrol and bioactive properties in table wines from organic and conventional production system

    Directory of Open Access Journals (Sweden)

    E. C. Perin

    2014-03-01

    Full Text Available The health benefits by consumption wine have been linked to presence of bioactive compounds in particular, anthocyanins, phenolic compounds, resveratrol and quercetin. The type and form of grape production, as well as processing affect these wine properties. In this study was evaluated the physical-chemical characteristics and the bioactive compounds of table wines from cv. 'Bordô' from conventional and organic production systems,  produced in the southwestern region of Paraná - Brazil. The processing conditions similar of the wines propitiated physical-chemical characteristics similar. The levels of bioactive compounds of the wine cv. 'Bordô' (Organic and Conventional had significant indexes, particularly the resveratrol. On average, the samples values are higher than the rates of other producing regions of Brazil. The organic production system showed higher rates for total phenolics compounds and anthocyanins and consequently higher antioxidant activity (EC50. The wines showed greater and significant correlation between antioxidant activity and content of anthocyanins.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. The effect of resveratrol on pharmacokinetics of aripiprazole in vivo and in vitro.

    Science.gov (United States)

    Zhan, Yun-Yun; Liang, Bing-Qing; Li, Xiang-Yu; Gu, Er-Min; Dai, Da-Peng; Cai, Jian-Ping; Hu, Guo-Xin

    2016-05-01

    1. The objective of this study were to investigate the effect of orally administered resveratrol on the pharmacokinetics of aripiprazole (APZ) in rat, and the inhibitory effects of resveratrol on APZ dehydrogenation activity in liver microsomes and human cytochrome P450 3A4 and 2D6. 2. Twenty-five healthy male Sprague-Dawley rats were randomly divided into five groups: A (control group), B (multiple dose of 200 mg/kg resveratrol), C (multiple dose of 100 mg/kg resveratrol), D (a single dose of 200 mg/kg resveratrol) and E (a single dose of 100 mg/kg resveratrol). A single dose of 3 mg/kg APZ administered orally 30 min after administration of resveratrol. In addition, CYP2D6*1, CYP3A4*1, human and rat liver microsomes were performed to determine the effect of resveratrol on the metabolism of APZ in vitro. 3. The multiple dose of 200 or 100 mg/kg resveratrol significantly increased the AUC and Cmax of APZ. The resveratrol also obviously decreased the CL, but without any significant difference on t1/2 in vivo. On the other hand, resveratrol showed inhibitory effect on CYP3A4*1, CYP2D6*1, human and rat microsomes, the IC50 of resveratrol was 6.771, 87.87, 45.11 and 35.59 μmol l(-1), respectively. 4. Those results indicated more attention should be paid when APZ was administrated combined with resveratrol. PMID:26391142

  20. 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.

  1. Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury

    OpenAIRE

    Fu-Chao Liu; Hsin-I Tsai; Huang-Ping Yu

    2015-01-01

    Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is...

  2. Free resveratrol monomers in varietal red and white wines from Dalmatia (Croatia

    OpenAIRE

    Katalinić, Višnja; Ljubenkov, Ivica; Pezo, Ivan; Generalić, Ivana; Stričević, Olivera; Miloš, Mladen; Modun, Darko; Boban, Mladen

    2008-01-01

    Introduction: Resveratrol is considered to be one of the major antioxidant constituents in red wine. In this article we investigated the presence of, and relation between trans- and cis-resveratrol monomers in the most characteristic varietal wines from Dalmatia (Croatia), produced according to the Croatian appellation of origin system. Materials and Methods: The wines of red grape varieties (Plavac mali, Merlot,Cabernet sauvignon, Babić, Plavina, Trnjak, Vranac and Lasin) and white grap...

  3. 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...

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

    OpenAIRE

    Ma, Xingrong; Sun, Zhikun; Liu, Yanru; Jia, Yanjie; Zhang, Boai; ZHANG, JIEWEN

    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...

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

    International Nuclear Information System (INIS)

    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)

  6. 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.

  7. 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)

  8. 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 be...

  9. Reaction kinetics of resveratrol with thiyl and alkoxyl radicals

    International Nuclear Information System (INIS)

    Complete text of publication follows. Plant derived resveratrol (trans-3,5,4'-trihydroxystilbene) possesses a broad spectrum of biological activities, one of them are very well known its antioxidative properties. Our work aims to provide kinetic data with regard to the reactivity of resveratrol with uninvestigated short-lived bioradicals, identified as mediators in oxidative lipid degradation processes. Radicals of our interest are alkoxyl radicals, well known propagators of the chain free radical reactions in lipids, and thiyl radicals which protect lipids from their degradation pathway, but at the same time cause the isomerization of the double bonds. In order to investigate these reactions of resveratrol laser flash photolysis was used. On the basis of competitive kinetics the rate constants were determined under pseudo-first order conditions in acetonitrile solutions at room temperature. Thiyl radicals were generated indirectly in solution containing 1-octadecanthiol and photosensitive benzophenone in acetonitrile using the light pulses at 347 nm from ruby laser. Tert-butoxyl radicals were generated directly by peroxide bond cleavage from di-tert-butyl peroxide in acetonitrile by light pulses of Nd:YAG at 355 nm, and ruby at 347 nm. Obtained rate constants for the reactions of resveratrol and radicals generated by laser flash photolysis will be summarized and compared with rare literature data for the rate constants of investigated reactions of resveratrol and other radicals generated by pulse radiolysis.

  10. Colloidal mesoporous silica nanoparticles enhance the biological activity of resveratrol.

    Science.gov (United States)

    Summerlin, Natalie; Qu, Zhi; Pujara, Naisarg; Sheng, Yong; Jambhrunkar, Siddharth; McGuckin, Michael; Popat, Amirali

    2016-08-01

    The naturally occurring polyphenol resveratrol (RES) has attracted increasing attention in recent years due to its antioxidant, anti-inflammatory, and anticancer activity. However, resveratrol's promising potential as a nutraceutical is hindered by its poor aqueous solubility, which limits its biological activity. Here we show that encapsulating resveratrol in colloidal mesoporous silica nanoparticles (MCM-48-RES) enhances its saturated solubility by ∼95% and increases its in vitro release kinetics compared to pure resveratrol. MCM-48-RES showed high loading capacity (20% w/w) and excellent encapsulation efficiency (100%). When tested against HT-29 and LS147T colon cancer cell lines, MCM-48-RES-mediated in vitro cell death was higher than that of pure resveratrol, mediated via the PARP and cIAP1 pathways. Finally, MCM-48-RES treatment also inhibited lipopolysaccharide-induced NF-κB activation in RAW264.7 cells, demonstrating improved anti-inflammatory activity. More broadly, our observations demonstrate the potential of colloidal mesoporous silica nanoparticles as next generation delivery carriers for hydrophobic nutraceuticals. PMID:27060664

  11. 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.

  12. 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

  13. 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)

  14. 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 ...

  15. 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.

  16. Antioxidant and anti-inflammatory properties of tomato fruits synthesizing different amounts of stilbenes.

    Science.gov (United States)

    D'Introno, Annalisa; Paradiso, Annalisa; Scoditti, Egeria; D'Amico, Leone; De Paolis, Angelo; Carluccio, M Annunziata; Nicoletti, Isabella; DeGara, Laura; Santino, Angelo; Giovinazzo, Giovanna

    2009-06-01

    Resveratrol, a plant phenolic compound, is found in grapes and red wine, but is not widely distributed in other common food sources. The pathway for resveratrol biosynthesis is well characterized. Metabolic engineering of this compound has been achieved in tomato plants (Lycopersicon esculentum Mill.) in order to improve their nutritional value. Tomato plants synthesizing resveratrol were obtained via the heterologous expression of a grape (Vitis vinifera L.) cDNA encoding for the enzyme stilbene synthase (StSy), under the control of the fruit-specific promoter TomLoxB. The resulting LoxS transgenic plants accumulated trans-resveratrol and trans-piceid, in particular in the skin of the mature fruits. Quantitative analyses carried out on LoxS fruits were compared with those of a tomato line constitutively expressing the stsy gene (35SS). The LoxS fruits contained levels of trans-resveratrol that were 20-fold lower than those previously reported for the 35SS line. The total antioxidant capability and ascorbate content in transformed fruits were also evaluated, and a significant increase in both was found in the LoxS and 35SS lines. These results could explain the higher capability of transgenic fruits to counteract the pro-inflammatory effects of phorbol ester in monocyte-macrophages via the inhibition of induced cyclo-oxygenase-2 enzyme. PMID:19490505

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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)

  2. 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...

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Effects of resveratrol and genistein on nuclear factor-κB, tumor necrosis factor-α and matrix metalloproteinase-9 in patients with chronic obstructive pulmonary disease

    Science.gov (United States)

    LIU, XIAO-JU; BAO, HAI-RONG; ZENG, XIAO-LI; WEI, JUN-MING

    2016-01-01

    Chronic airway inflammation and airway remodeling are the major pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Resveratrol and genistein have been previously demonstrated to have anti-inflammatory and antioxidative properties. The present study aimed to measure the inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 concentration in patients with COPD. Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy subjects, then randomly divided into the following four treatment groups: Control, dexamethasone (0.5 µmol/l), resveratrol (12.5 µmol/l) and genistein (25 µmol/l) groups. After 1 h of treatment, 100 µl lymphocytes were collected for nuclear factor (NF)-κB immunocytochemical staining. After 48 h treatment, the supernatant of the lymphocytes was collected for analysis of TNF-α and MMP-9 concentration levels. The percentage of lymphocytes with positive nuclear NF-κB expression was analyzed by immunocytochemical staining. The concentration levels of TNF-α and MMP-9 were measured using radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The present study demonstrated that the percentage of NF-κB-positive cells, and the levels of TNF-α and MMP-9 in lymphocytes from patients with COPD patients were significantly higher compared with healthy subjects. Additionally, there were positive correlations between the percentage of NF-κB-positive cells, and the concentration levels of TNF-α and MMP-9 in patients with COPD. All three factors were significantly reduced in lymphocytes treated with resveratrol and genistein, and the inhibitory effects of resveratrol on NF-κB, TNF-α and MMP-9 were more potent than the effects of genistein. In conclusion, resveratrol and genistein may inhibit the NF-κB, TNF-α and MMP-9-associated pathways in patients with COPD. It is suggested that resveratrol and genistein may be potential

  6. 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

  7. 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.

  8. Effect of resveratrol or ascorbic acid on the stability of α-tocopherol in O/W emulsions stabilized by whey protein isolate: Simultaneous encapsulation of the vitamin and the protective antioxidant.

    Science.gov (United States)

    Wang, Lei; Gao, Yahui; Li, Juan; Subirade, Muriel; Song, Yuanda; Liang, Li

    2016-04-01

    Food proteins have been widely used as carrier materials due to their multiple functional properties. Hydrophobic bioactives are generally dissolved in the oil phase of O/W emulsions. Ligand-binding properties provide the possibility of binding bioactives to the protein membrane of oil droplets. In this study, the influence of whey protein isolate (WPI) concentration and amphiphilic resveratrol or hydrophilic ascorbic acid on the decomposition of α-tocopherol in the oil phase of WPI emulsions is considered. Impact of ascorbic acid, in the continuous phase, on the decomposition depended on the vitamin concentration. Resveratrol partitioned into the oil-water interface and the cis-isomer contributed most of the protective effect of this polyphenol. About 94% of α-tocopherol and 50% of resveratrol were found in the oil droplets stabilized by 0.01% WPI. These results suggest the feasibility of using the emulsifying and ligand-binding properties of WPI to produce carriers for simultaneous encapsulation of bioactives with different physicochemical properties. PMID:26593516

  9. Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.

    Science.gov (United States)

    Du, Qin; Hu, Bing; An, Hong-Mei; Shen, Ke-Ping; Xu, Ling; Deng, Shan; Wei, Meng-Meng

    2013-05-01

    Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine. PMID:23446753

  10. 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

  11. Resveratrol exerts no effect on inflammatory response and delayed onset muscle soreness after a marathon in male athletes. A randomised, double-blind, placebo-controlled pilot feasibility study

    OpenAIRE

    2014-01-01

    Objective: We investigated whether the inflammatory response and delayed onset of muscle soreness after a marathon are altered by resveratrol, a natural polyphenolic flavonoid antioxidant. Design: Double blind placebo-controlled randomised pilot study. Setting: London Marathon. Participants: Marathon race participants. Interventions: 7 healthy male athletes were randomised to receive Resveratrol (600 mg Resveratrol daily for 7 days immediately before the marathon) or a placebo. ...

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. 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.

  15. 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

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

    Science.gov (United States)

    Friedrich, Rossana B; Kann, Birthe; Coradini, Karine; Offerhaus, Herman L; Beck, Ruy C R; Windbergs, Maike

    2015-10-12

    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 therapeutic effect, increased activity was reported upon co-delivery of the two compounds. However, due to the poor water solubility of resveratrol and curcumin, their clinical application is currently limited. In this context, lipid-core nanocapsules (LNC) composed of an oily core surrounded by a polymeric shell were introduced as drug carrier systems with the potential to overcome this obstacle. Furthermore, the encapsulation of polyphenols into LNC can increase their photostability. As the attributes of the polyphenols make them excellent candidates for skin treatment, the aim of this study was to investigate the effect of co-delivery of resveratrol and curcumin by LNC upon topical application on excised human skin. In contrast to the formulation with one polyphenol, resveratrol penetrated into deeper skin layers when the co-formulation was applied. Based on vibrational spectroscopy analysis, these effects are most likely due to interactions of curcumin and the stratum corneum, facilitating the skin absorption of the co-administered resveratrol. Furthermore, the interaction of LNC with primary human skin cells was analyzed encountering a cellular uptake within 24h potentially leading to intracellular effects of the polyphenols. Thus, the simultaneous delivery of resveratrol and curcumin by LNC provides an intelligent way for immediate and sustained polyphenol delivery for skin disease treatment. PMID:26215463

  17. Resveratrol: Anti-Obesity Mechanisms of Action

    OpenAIRE

    Leixuri Aguirre; Alfredo Fernández-Quintela; Noemí Arias; Maria P. Portillo

    2014-01-01

    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-adip...

  18. 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

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Post-harvest induced production of salvianolic acids and significant promotion of antioxidant properties in roots of Salvia miltiorrhiza (Danshen).

    Science.gov (United States)

    Zhou, Guo-Jun; Wang, Wei; Xie, Xiao-Mei; Qin, Min-Jian; Kuai, Ben-Ke; Zhou, Tong-Shui

    2014-01-01

    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. PMID:24886944

  3. 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.

  4. 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

  5. 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...... solutions in DMSO were equilibrated against pentane solutions. From the UV-vis absorbance of resveratrol in the DMSO phase, P* = 1.74 × 10−3 was determined. The mutual miscibility of pentane and DMSO, measured by 1H-NMR spectroscopy, was taken into account. The value of P* indicates a preference of...

  6. Anti-inflammatory effects of resveratrol: possible role in prevention of age-related cardiovascular disease

    OpenAIRE

    Csiszar, Anna

    2011-01-01

    Cardiovascular diseases are the most common cause of death among the elderly in the Western world. Resveratrol (3,5,4´-trihydroxystilbene) is a plant-derived polyphenol that was shown to exert diverse anti-aging activity mimicking some of the molecular and functional effects of caloric restriction. This mini-review focuses on the molecular and cellular mechanisms activated by resveratrol in the vascular system, and explores the links between its anti-oxidative and anti-inflammatory effects, w...

  7. Stability of Trans-Resveratrol Encapsulated in a Protein Matrix Produced Using Spray Drying to UV Light Stress and Simulated Gastro-Intestinal Digestion.

    Science.gov (United States)

    Koga, Clarissa C; Andrade, Juan E; Ferruzzi, Mario G; Lee, Youngsoo

    2016-02-01

    Trans-resveratrol has demonstrated the potential to provide both therapeutic and preventive activities against chronic diseases such as heart disease and cancer. The incorporation of trans-resveratrol into food products would allow for broader access of this bioactive compound to a larger population. However, this strategy is limited by instability of trans-resveratrol under environmental conditions and within the digestive system leading to isomerization of trans-resveratrol (bioactive form) to cis-resveratrol (bio-inactive form). Studies in the stabilization of trans-resveratrol into protein microparticles are presented. Trans-resveratrol was encapsulated using whey protein concentrate (WPC) or sodium caseinate (SC), with or without anhydrous milk fat (AMF). Binding of resveratrol and aromatic residues in protein was estimated utilizing the Stern-Volmer equation and the number of tryptophan residues. The stability of encapsulated resveratrol was evaluated after exposure to ultraviolet A (UVA) light and 3-stage in vitro digestion. After UVA light exposure, SC-based microcapsules maintained a higher trans:cis resveratrol ratio (0.63, P < 0.05) than WPC-based microcapsules (0.43) and unencapsulated resveratrol (0.49). In addition, encapsulation of resveratrol in both protein microparticles led to an increased digestive stability and bioaccessibility in comparison to unencapsulated resveratrol (47% and 23%, respectively, P < 0.05). SC-based microcapsules provided a higher digestive stability and bioaccessibility (86% and 81%; P < 0.05) compared to WPC-based microcapsules (71% and 68%). The addition of AMF to the microcapsules did not significantly change the in vitro digestion values. In conclusion, SC-based microencapsulation increased the stability of trans-resveratrol to UVA light exposure and simulated digestion conditions. This encapsulation-system-approach can be extended to other labile, bioactive polyphenols. PMID:26677808

  8. Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Bruckbauer A

    2013-02-01

    Full Text Available Antje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB, acts synergistically with low doses of metformin to impact insulin sensitivity and AMP-activated protein kinase-dependent outcomes in cell culture and in diabetic mice.Methods: C2C12 skeletal myotubes and 3T3-L1 adipocytes were treated with resveratrol 0.2 µM, HMB 5 µM, and metformin 0.1 mM alone or in combination. db/db mice were treated for 2 weeks with high (1.5 g/kg diet, low (0.75 g/kg diet, or very low (0.25 g/kg diet doses of metformin alone or in combination with a diet containing resveratrol 12.5 mg and CaHMB 2 g/kg.Results: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone. A similar trend was found in 3T3L1 adipocytes. In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMAIR, plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. In addition, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice.Conclusion: Resveratrol-HMB combined with metformin may act synergistically on AMP-activated protein kinase-dependent pathways, leading to increased insulin sensitivity, which may reduce the therapeutic doses of metformin necessary in the treatment of diabetes.Keywords: diabetes, AMP-activated protein kinase, Sirt1, fat oxidation

  9. 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.

  10. Influence of resveratrol release on the tissue response to mechanically adaptive cortical implants.

    Science.gov (United States)

    Nguyen, Jessica K; Jorfi, Mehdi; Buchanan, Kelly L; Park, Daniel J; Foster, E Johan; Tyler, Dustin J; Rowan, Stuart J; Weder, Christoph; Capadona, Jeffrey R

    2016-01-01

    The stability and longevity of recordings obtained from intracortical microelectrodes continues to remain an area of concern for neural interfacing applications. The limited longevity of microelectrode performance has been associated with the integrity of the blood brain barrier (BBB) and the neuroinflammatory response to the microelectrode. Here, we report the investigation of an additive approach that targets both mechanical and chemical factors believed to contribute to chronic BBB instability and the neuroinflammatory response associated with implanted intracortical microelectrodes. The implants investigated were based on a mechanically adaptive, compliant nanocomposite (NC), which reduces the tissue response and tissue strain. This material was doped with various concentrations of the antioxidant resveratrol with the objective of local and rapid delivery. In vitro analysis of resveratrol release, antioxidant activity, and cytotoxicity suggested that a resveratrol content of 0.01% was optimal for in vivo assessment. Thus, probes made from the neat NC reference and probes containing resveratrol (NC Res) were implanted into the cortical tissue of rats for up to sixteen weeks. Histochemical analysis suggested that at three days post-implantation, neither materials nor therapeutic approaches (independently or in combination) could alter the initial wound healing response. However, at two weeks post-implantation, the NC Res implant showed a reduction in activated microglia/macrophages and improvement in neuron density at the tissue-implant interface when compared to the neat NC reference. However, sixteen weeks post-implantation, when the antioxidant was exhausted, NC Res and the neat NC reference exhibited similar tissue responses. The data show that NC Res provides short-term, short-lived benefits due to the antioxidant release, and a long-term reduction in neuroinflammation on account of is mechanical adaptive, compliant nature. Together, these results

  11. 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

  12. 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.

  13. 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.

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

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    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.

  15. 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.

  16. 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 ...

  17. 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.

  18. 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.

  19. 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.

  20. Resveratrol and health from a consumer perspective

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-01-01

    resveratrol consumer studies with Danish and U.S. consumers to look at current findings and future research directions for three questions. (1)Which factors determine consumer interest in a yet unknown functional ingredient such as resveratrol? (2)Howshould resveratrol bemarketed as a new functional......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...... ingredient to be understood and favorably perceived? (3) What could be the effects of adoption of an ingredient such as resveratrol on the healthy lifestyle of a consumer? Literature and first results indicate that personal relevance and familiarity are crucial factors; however, consumers show little...

  1. Amino Acid Carbamates As Prodrugs Of Resveratrol.

    Science.gov (United States)

    Mattarei, Andrea; Azzolini, Michele; La Spina, Martina; Zoratti, Mario; Paradisi, Cristina; Biasutto, Lucia

    2015-01-01

    Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted carbamate ester (-OC(O)NHR) linkage with a natural amino acid (Leu, Ile, Phe, Thr) to prevent conjugation and modulate the physicochemical properties of the molecule. We also report a convenient, high-yield protocol to obtain derivatives of this type. The new carbamate ester derivatives are stable at pH 1, while they undergo slow hydrolysis at physiological pH and hydrolyse with kinetics suitable for use in prodrugs in whole blood. After administration to rats by oral gavage the isoleucine-containing prodrug was significantly absorbed, and was present in the bloodstream as non-metabolized unaltered or partially deprotected species, demonstrating effective shielding from first-pass metabolism. We conclude that prodrugs based on the N-monosubstituted carbamate ester bond have the appropriate stability profile for the systemic delivery of phenolic compounds. PMID:26463125

  2. 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.

  3. 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

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

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    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.

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

    Science.gov (United States)

    Riebel, Matthias; Sabel, Andrea; Claus, Harald; Fronk, Petra; Xia, Ning; Li, Huige; König, Helmut; Decker, Heinz

    2015-01-01

    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. PMID:26393557

  6. Photostability evaluation of five UV-filters, trans-resveratrol and beta-carotene in sunscreens.

    Science.gov (United States)

    Freitas, Juliana Vescovi; Lopes, Norberto Peporine; Gaspar, Lorena Rigo

    2015-10-12

    Trans-resveratrol (RES) is used in cosmetic formulations and beta-carotene (BTC) is a classical sunscreen antioxidant, but their photostability in sunscreens, a property directly correlated to performance and safety has not been addressed in the literature. This paper reports the assessment of RES and/or BTC influence on the photostability of five UV-filters (octyl methoxycinnamate - OMC, avobenzone -AVO, octocrylene - OCT, bemotrizinole - BMZ, octyltriazone - OTZ) in three different combinations after UVA exposure followed by the identification of degradation products and the assessment of photoreactivity. The evaluation of sunscreen photostability was performed by HPLC and spectrophotometric analysis, and degradation products were identified by GC-MS analysis. Components RES, BTC, OMC and AVO were significantly degraded after UV exposure (reduction of around 16% in recovery). According to HPLC analysis, all formulations presented similar photostability profiles. Eleven degradation products were identified in GC-MS analysis, among them products of RES, BTC, OMC and AVO photodegradation. All evaluated formulations were considered photoreactive, as well as the isolated compounds RES and AVO. Considering HPLC, spectrophotometric and GC-MS results, it is suggested that formulations containing BMZ were considered the most photostable. The combination RES+BTC in a sunscreen improved the photostability of AVO. The benefits of using a combination of antioxidants in sunscreens was demonstrated by showing that using RES+BTC+studied UV-filters led to more photostable formulations, which in turn implies in better safety and efficacy. PMID:26159738

  7. 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.

  8. 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.

  9. 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.

  10. Antimicrobial activity of resveratrol analogues.

    Science.gov (United States)

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    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. PMID:24918540

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

    Science.gov (United States)

    Gu, Hailun; Li, Keyu; Li, Xingyao; Yu, Xiaolu; Wang, Wei; Ding, Lifeng; Liu, Li

    2016-01-01

    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. PMID:27104565

  12. 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.

  13. Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin

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    Jin-Ah Lee

    2015-11-01

    Full Text Available The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs in HepG2 cells were stimulated with lipopolysaccharide (LPS. ARMs prominently inhibited (p < 0.05 the production of nitric oxide (NO, prostaglandin E2 (PGE2, interleukin (IL-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs. ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2. Co-administration of apigenin (50 mg/kg and resveratrol (25 mg/kg also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%. Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs, was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin’s anti-inflammatory activities in the body.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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...

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

    International Nuclear Information System (INIS)

    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)

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

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    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.

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

    Science.gov (United States)

    Barbosa, Gabriella Lopes de Rezende; Pimenta, Luiz André; Almeida, Solange Maria de

    2016-01-01

    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. PMID:26981750

  2. 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)

  3. Recent advance on the antitumor and antioxidant activity of grape seed extracts

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    Zhu FM

    2015-05-01

    Full Text Available Fengmei Zhu, Bin Du, Jun Li College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, Hebei Province, People's Republic of China Abstract: The grape pomace (including seeds and stems poses potential disposal and pollution problems along with loss of valuable biomass and nutrients. The utilization of grape seeds processing as a source of functional ingredients is a promising field. Grape seed extract provides a concentrated source of polyphenols. Grape seed extract is known as an effective antioxidant that protects the body from premature aging and disease. A number of phytochemicals including resveratrol, proanthocyanidins, etc, have demonstrated significant benefits in cancer chemoprevention. In this review, we summarize the existing knowledge on the antitumor and antioxidant activity of grape seeds polyphenols. Keywords: grape seed, antitumor activity, antioxidant activity, polyphenol, proanthocyanidin

  4. Resveratrol couples apoptosis with autophagy in UVB-irradiated HaCaT cells.

    Directory of Open Access Journals (Sweden)

    Nicoletta Vitale

    Full Text Available UVB radiation causes about 90% of non-melanoma skin cancers by damaging DNA either directly or indirectly by increasing levels of reactive oxygen species (ROS. Skin, chronically exposed to both endogenous and environmental pro-oxidant agents, contains a well-organised system of chemical and enzymatic antioxidants. However, increased or prolonged free radical action can overwhelm ROS defence mechanisms, contributing to the development of cutaneous diseases. Thus, new strategies for skin protection comprise the use of food antioxidants to counteract oxidative stress. Resveratrol, a phytoalexin from grape, has gained a great interest for its ability to influence several biological mechanisms like redox balance, cell proliferation, signal transduction pathways, immune and inflammatory response. Therefore, the potential of resveratrol to modify skin cell response to UVB exposure could turn out to be a useful option to protect skin from sunlight-induced degenerative diseases. To investigate into this matter, HaCaT cells, a largely used model for human skin keratinocytes, were treated with 25 or 100 µM resveratrol for 2 and 24 hours prior to UVB irradiation (10 to 100 mJ/cm(2. Cell viability and molecular markers of proliferation, oxidative stress, apoptosis, and autophagy were analyzed. In HaCaT cells resveratrol pretreatment: reduces UVB-induced ROS formation, enhances the detrimental effect of UVB on HaCaT cell vitality, increases UVB-induced caspase 8, PARP cleavage, and induces autophagy. These findings suggest that resveratrol could exert photochemopreventive effects by enhancing UVB-induced apoptosis and by inducing autophagy, thus reducing the odds that damaged cells could escape programmed cell death and initiate malignant transformation.

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

    International Nuclear Information System (INIS)

    (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 IC50 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 G2/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 PDEs, SIRT1, or

  6. 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

  7. Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats

    Directory of Open Access Journals (Sweden)

    Whitsett Timothy

    2006-05-01

    Full Text Available Abstract Despite the advent of new and aggressive therapeutics, breast cancer remains a leading killer among women; hence there is a need for the prevention of this disease. Several naturally occurring polyphenols have received much attention for their health benefits, including anti-carcinogenic properties. Two of these are resveratrol, a component of red grapes, and epigallocatechin-3-gallate (EGCG, the major catechin found in green tea. In this study, we tested the hypothesis that these two polyphenols protect against chemically-induced mammary cancer by modulating mammary gland architecture, cell proliferation, and apoptosis. Female Sprague-Dawley CD rats were exposed to either resveratrol (1 g/kg AIN-76A diet, EGCG (0.065% in the drinking water, or control diet (AIN-76A for the entirety of their life starting at birth. At 50 days postpartum, rats were treated with 60 mg dimethylbenz[a]anthracene (DMBA/kg body weight to induce mammary cancer. Resveratrol, but not EGCG, suppressed mammary carcinogenesis (fewer tumors per rat and longer tumor latency. Analysis of mammary whole mounts from 50-day-old rats revealed that resveratrol, but not EGCG, treatment resulted in more differentiated lobular structures. Bromodeoxyuridine (BrdU incorporation studies showed that resveratrol treatment caused a significant reduction in proliferative cells in mammary terminal ductal structures at 50 days postpartum, making them less susceptible to carcinogen insult. The epithelial cells of terminal end buds in the mammary glands of resveratrol-treated rats also showed an increase in apoptotic cells compared to the control or EGCG-treated rats as measured by a DNA fragmentation assay. At the given doses, resveratrol treatment resulted in a serum resveratrol concentration of 2.00 μM, while treatment with EGCG resulted in a serum EGCG concentration of 31.06 nM. 17β-Estradiol, progesterone, and prolactin concentrations in the serum were not significantly affected

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Resveratrol Protects against TNF-α-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK.

    Science.gov (United States)

    Pan, Wei; Yu, Huizhen; Huang, Shujie; Zhu, Pengli

    2016-01-01

    Inflammation and reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerosis. Resveratrol has been shown to possess anti-inflammatory and antioxidative stress activities, but the underlying mechanisms are not fully understood. In the present study, we investigated the molecular basis associated with the protective effects of resveratrol on tumor necrosis factor-alpha (TNF-α)-induced injury in human umbilical endothelial cells (HUVECs) using a variety of approaches including a cell viability assay, reverse transcription and quantitative polymerase chain reaction, western blot, and immunofluorescence staining. We showed that TNF-α induced CD40 expression and ROS production in cultured HUVECs, which were attenuated by resveratrol treatment. Also, resveratrol increased the expression of sirtuin 1 (SIRT1); and repression of SIRT1 by small-interfering RNA (siRNA) and the SIRT1 inhibitor Ex527 reduced the inhibitory effects of resveratrol on CD40 expression and ROS generation. In addition, resveratrol downregulated the levels of p65 and phospho-p38 MAPK, but this inhibitory effect was attenuated by the suppression of SIRT1 activity. Moreover, the p38 MAPK inhibitor SD203580 and the nuclear factor (NF)-κB inhibitor pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as resveratrol on TNF-α-induced ROS generation and CD40 expression. Thus, our study provides a mechanistic link between resveratrol and the activation of SIRT1, the latter of which is involved in resveratrol-mediated repression of the p38 MAPK/NF-κB pathway and ROS production in TNF-α-treated HUVECs. PMID:26799794

  13. Polycaprolactone scaffold engineered for sustained release of resveratrol: therapeutic enhancement in bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Kamath MS

    2013-12-01

    Full Text Available Manjunath Srinivas Kamath,1 Shiek SSJ Ahmed,2 M Dhanasekaran,3 S Winkins Santosh11Department of Biotechnology, School of Bioengineering, SRM University, 2Department of Biotechnology, Chettinad Hospital and Research Institute, 3Department of Stem Cells, Life Line Rigid Hospital Pvt Ltd, Kilpauk, Tamil Nadu, IndiaAbstract: Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycaprolactone (PCL scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively induced by PCL-RNP compared with the PCL scaffold (the positive control. Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering.Keywords: therapeutic scaffolds, polycaprolactone scaffolds, bone tissue engineering, resveratrol, albumin nanoparticles

  14. 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...

  15. Resveratrol induces the expression of interleukin-10 and brain-derived neurotrophic factor in BV2 microglia under hypoxia.

    Science.gov (United States)

    Song, Juhyun; Cheon, So Yeong; Jung, Wonsug; Lee, Won Taek; Lee, Jong Eun

    2014-01-01

    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. PMID:25184950

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. A new approach to elucidating repair reactions of resveratrol.

    Science.gov (United States)

    Kerzig, Christoph; Henkel, Selgar; Goez, Martin

    2015-06-01

    The repair by co-antioxidants of the phenoxy radical of resveratrol, the famous health-preserving ingredient of red wine, is a key step of radical scavenging cascades in nature. To generate that radical, we employed 355 nm photoionization as a direct and selective access that reduces the chemical complexity and is equally applicable in organized phases; to monitor it, we used its hitherto unreported absorption in the red where no other species in our systems interfere. With this novel approach, we measured rate constants and H/D kinetic isotope effects for the repairs by ascorbate, trolox (a vitamin E analogue) and 4-aminophenol, and identified the mechanisms as one-step hydrogen abstractions. Cysteine and glutathione are unreactive. In micellar solution (SDS), the repair by ascorbate is much slower and involves only the hydrophilic phenoxy moieties protruding from the micelles. The new experimental strategy also led to a reevaluation of extinction coefficients, rate constants and mechanisms. PMID:25948021

  19. 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)

  20. 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. PMID:27150769

  1. Amino Acid Carbamates As Prodrugs Of Resveratrol

    OpenAIRE

    Andrea Mattarei; Michele Azzolini; Martina La Spina; Mario Zoratti; Cristina Paradisi; Lucia Biasutto

    2015-01-01

    Resveratrol (3, 5, 4′-trihydroxy-trans-stilbene), a plant polyphenol, has important drug-like properties, but its pharmacological exploitation in vivo is hindered by its rapid transformation via phase II conjugative metabolism. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, stability and in vivo pharmacokinetic behaviour of prodrugs of resveratrol in which the OH groups are engaged in an N-monosubstituted carbamate ester (-OC(O)NHR) lin...

  2. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. 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

  6. 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

  7. Design and synthesis of resveratrol-salicylate hybrid derivatives as CYP1A1 inhibitors.

    Science.gov (United States)

    Aldawsari, Fahad S; Elshenawy, Osama H; El Gendy, Mohamed A M; Aguayo-Ortiz, Rodrigo; Baksh, Shairaz; El-Kadi, Ayman O S; Velázquez-Martínez, Carlos A

    2015-12-01

    Resveratrol and aspirin are known to exert potential chemopreventive effects through modulation of numerous targets. Considering that the CYP450 system is responsible for the activation of environmental procarcinogens, the aim of this study was to design a new class of hybrid resveratrol-aspirin derivatives possessing the stilbene and the salicylate scaffolds. Using HepG2 cells, we evaluated (a) the inhibition of TCDD-mediated induction of CYP1A1 exerted by resveratrol-aspirin derivatives using the EROD assay, and (b) CYP1A1 mRNA in vitro. We observed significant inhibition (84%) of CYP1A1 activity and a substantial decrease in CYP1A1 mRNA with compound 3, compared to control. Resveratrol did not exert inhibition under the same experimental conditions. This inhibitory profile was supported by docking studies using the crystal structure of human CYP1A1. The potential effect exerted by compound 3 (the most active), provide preliminary evidence supporting the design of hybrid molecules combining the chemical features of resveratrol and aspirin. PMID:25407017

  8. 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.

  9. Synthesis and Biological Evaluation of Novel Resveratrol-NSAID Derivatives as Anti-inflammatory Agents.

    Science.gov (United States)

    Peng, Wei; Ma, Yan-Yan; Zhang, Kun; Zhou, Ai-Yu; Zhang, Yu; Wang, Huaqian; Du, Zhiyun; Zhao, Deng-Gao

    2016-06-01

    Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol-ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases. PMID:27009373

  10. 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

  11. Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy.

    Directory of Open Access Journals (Sweden)

    José Díaz-Chávez

    Full Text Available The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC >2.0; p≤0.05 in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS as heat shock protein 27 (HSP27, translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27

  12. 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...

  13. Neuroprotective effects of resveratrol against traumatic brain injury in rats: Involvement of synaptic proteins and neuronal autophagy.

    Science.gov (United States)

    Feng, Yan; Cui, Ying; Gao, Jun-Ling; Li, Ran; Jiang, Xiao-Hua; Tian, Yan-Xia; Wang, Kai-Jie; Li, Ming-Hang; Zhang, Hong-Ao; Cui, Jian-Zhong

    2016-06-01

    Traumatic brain injury (TBI) involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death, leading to long‑term cognitive deficits, and effective therapeutic strategies targeting neuronal death remain elusive. The present study aimed to determine whether the administration of resveratrol (100 mg/kg) was able to significantly enhance functional recovery in a rat model of TBI and whether resveratrol treatment was able to upregulate synaptic protein expression and suppress post‑TBI neuronal autophagy. The results demonstrated that daily treatment with resveratrol attenuated TBI‑induced brain edema and improved spatial cognitive function and neurological impairment in rats. The expression of synaptic proteins was downregulated following TBI and this phenomenon was partly reversed by treatment with resveratrol. In addition, resveratrol was observed to significantly reduce the levels of the autophagic marker proteins, microtubule‑associated protein light chain 3‑II and Beclin1, in the hippocampus compared with the TBI group. Therefore, these results suggest that resveratrol may represent a novel therapeutic strategy for TBI, and that this protection may be associated with the upregulation of synaptophysin, postsynaptic density protein 95 and the suppression of neuronal autophagy. PMID:27122047

  14. 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

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

    Directory of Open Access Journals (Sweden)

    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

  16. 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...... assessed in lipopolysaccharide (LPS)-stimulated human monocytes mono mac 6. The isolated AF, containing six different anthocyanins, exhibited a stronger antioxidative capacity compared to resveratrol. Resveratrol enhanced tumor necrosis factor-alpha and reduced interleukin-10 (IL-10) production by LPS...

  17. Resveratrol augments therapeutic efficiency of mouse bone marrow mesenchymal stem cell-based therapy in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Wang, Dong; Li, Shi-Ping; Fu, Jin-Sheng; Bai, Lin; Guo, Li

    2016-04-01

    Experimental autoimmune encephalitis (EAE) is an inflammatory demyelinating disease, which served as a useful model providing considerable insights into the pathogenesis of multiple sclerosis (MS). Mouse bone marrow mesenchymal stem cells (mBM-MSC) were shown to have neuroprotection capabilities in EAE. Resveratrol is a small polyphenolic compound and possess therapeutic activity in various immune-mediated diseases. The sensitivity of mBM-MSCs to resveratrol was determined by an established cell-viability assay. Resveratrol-treated mBM-MSCs were also characterized with flow cytometry using MSC-specific surface markers and analyzed for their multiple differentiation capacities. EAE was induced in C57BL/6 mice by immunization with MOG35-55. Interferon gamma (IFN-γ)/tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4)/interleukin-10 (IL-10), the hallmark cytokines that direct T helper type 1 (Th1) and Th2 development, were detected with enzyme-linked immunosorbent assay (ELISA). In vivo efficacy experiments showed that mBM-MSCs or resveratrol alone led to a significant reduction in clinical scores, and combined treatment resulted in even more prominent reduction. The combined treatment with mBM-MSCs and resveratrol enhanced the immunomodulatory effects, showing suppressed proinflammatory cytokines (IFN-γ, TNF-α) and increased anti-inflammatory cytokines (IL-4, IL-10). The combination of mBM-MSCs and resveratrol provides a novel potential experimental protocol for alleviating EAE symptoms. PMID:26827767

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

    OpenAIRE

    Juhyun Song; So Yeong Cheon; Wonsug Jung; Won Taek Lee; Jong Eun Lee

    2014-01-01

    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,...

  19. 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

  20. 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.

  1. Resveratrol-loaded nanocapsules inhibit murine melanoma tumor growth.

    Science.gov (United States)

    Carletto, Bruna; Berton, Juliana; Ferreira, Tamara Nascimento; Dalmolin, Luciana Facco; Paludo, Katia Sabrina; Mainardes, Rubiana Mara; Farago, Paulo Vitor; Favero, Giovani Marino

    2016-08-01

    In this study, resveratrol-loaded nanocapsules were developed and its antitumor activity tested on a melanoma mice model. These nanocapsules were spherically-shaped and presented suitable size, negative charge and high encapsulation efficiency for their use as a modified-release system of resveratrol. Nanoencapsulation leads to the drug amorphization. Resveratrol-loaded nanoparticles reduced cell viability of murine melanoma cells. There was a decrease in tumor volume, an increase in the necrotic area and inflammatory infiltrate of melanoma when resveratrol-loaded nanocapsules were compared to free resveratrol in treated mice. Nanoencapsulation of resveratrol also prevented metastasis and pulmonary hemorrhage. This modified-release technology containing resveratrol can be used as a feasible approach in order to inhibit murine melanoma tumor growth. PMID:27070053

  2. Resveratrol Protects against Titanium Particle-Induced Aseptic Loosening Through Reduction of Oxidative Stress and Inactivation of NF-κB.

    Science.gov (United States)

    Luo, Guotian; Li, Ziqing; Wang, Yu; Wang, Haixing; Zhang, Ziji; Chen, Weishen; Zhang, Yangchun; Xiao, Yinbo; Li, Chaohong; Guo, Ying; Sheng, Puyi

    2016-04-01

    Aseptic implant loosening is closely associated with chronic inflammation induced by implant wear debris, and reactive oxygen species (ROS) play an important role in this process. Resveratrol, a plant compound, has been reported to act as an antioxidant in many inflammatory conditions; however, its protective effect and mechanism against wear particle-induced oxidative stress remain unknown. In this study, we evaluated resveratrol's protective effects against wear particle-induced oxidative stress in RAW 264.7 macrophages. At non-toxic concentrations, resveratrol showed dose-dependent inhibition of nitric oxide (NO) production, ROS generation, and lipid peroxidation. It also downregulated the gene expression of oxidative enzymes, including inducible nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-1 and NOX-2, and promoted the gene expression and activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx). This protective effect against wear particle-induced oxidative stress was accompanied by a reduction of gene expression and release of tumor necrosis factor-α (TNF-α), and decreased gene expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings demonstrate that resveratrol can inhibit wear particle-induced oxidative stress in macrophages, and may exert its antioxidant effect and protect against aseptic implant loosening. PMID:26878849

  3. Vascular Dysfunction in Aging: Potential Effects of Resveratrol, an Anti-Inflammatory Phytoestrogen

    OpenAIRE

    Labinskyy, Nazar; Csiszar, Anna; Veress, Gabor; Stef, Gyorgyi; Pacher, Pal; Oroszi, Gabor; Wu, Joseph; Ungvari, Zoltan

    2006-01-01

    Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing vascular oxidative stress and inflammation. Because the population in the Western world is rapidly aging, there is a substantial need for pharmacological interventions that delay the functional decline of the cardiovascular system. Resveratrol is an atoxic...

  4. 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

  5. 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

  6. NIH Researchers Find Resveratrol Helps Protect against Cardiovascular Disease in Animal Study

    Science.gov (United States)

    ... find Resveratrol helps protect against cardiovascular disease in animal study June 3, 2014 Resveratrol, a compound found ... translatable to humans. Multiple studies on resveratrol in animal models, however, have presented ample evidence to support ...

  7. 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

  8. 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

  9. Variability in the antioxidant activity of dietary supplements from pomegranate, milk thistle, green tea, grape seed, goji, and acai: effects of in vitro digestion.

    Science.gov (United States)

    Henning, Susanne M; Zhang, Yanjun; Rontoyanni, Victoria G; Huang, Jianjun; Lee, Ru-Po; Trang, Amy; Nuernberger, Gloria; Heber, David

    2014-05-14

    The antioxidant activity (AA) of fruits and vegetables has been thoroughly investigated but less is known about the AA of dietary supplements (DS). We therefore assessed the AA of three to five DS each from pomegranate, milk thistle, green tea, grapes, goji, and acai using four widely used standard methods. The secondary objective was to determine the effects of in vitro digestion on their AA. The AA of the DS prior to digestion ranked as follows: pomegranate > resveratrol > green tea > grape seed > milk thistle and very low in goji and acai with significant group variability in AA. The AA after in vitro simulated digestion of the mouth, stomach, and small intestine compared to undigested supplement was decreased for green tea and grape seed but increased for pomegranate, resveratrol, milk thistle, goji, and acai to various extents. Although polyphenols provide the major antioxidant potency of the tested supplements, our observations indicate that digestion may alter antioxidant properties depending in part on the variations in polyphenol content. PMID:24745654

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

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    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

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

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    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.

  12. 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...

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

    OpenAIRE

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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

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

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    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.

  2. 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.

  3. 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.

  4. 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

  5. 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 ...

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

    OpenAIRE

    Gianni Sacchetti; Roberto Gambari; Silvia Maietti; Monica Borgatti; Eleonora Brognara; Renato Bruni; Alessandra Guerrini; Damiano Rossi

    2012-01-01

    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 conte...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

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

    Science.gov (United States)

    Shi, Junling; Zeng, Qin; Liu, Yanlin; Pan, Zhongli

    2012-07-01

    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 microorganisms from selected plants that produce resveratrol and to optimize the conditions for resveratrol production. Endophytes from Merlot wine grapes (Vitis vinifera L. cv. Merlot), wild Vitis (Vitis quinquangularis Rehd.), and Japanese knotweed (Polygonum cuspidatum Siebold & Zucc.) were isolated, and their abilities to produce resveratrol were evaluated. A total of 65 isolates were obtained and 21 produced resveratrol (6-123 μg/L) in liquid culture. The resveratrol-producing isolates belonged to seven genera, Botryosphaeria, Penicillium, Cephalosporium, Aspergillus, Geotrichum, Mucor, and Alternaria. The resveratrol-producing capability decreased or was completely lost in most isolates after three rounds of subculture. It was found that only the strain Alternaria sp. MG1 (isolated from cob of Merlot using GA1 medium) had stable and high resveratrol-producing capability in all subcultures. During liquid cultivation of Alternaria sp. MG1 in potato dextrose medium, the synthesis of resveratrol began on the first day, increased to peak levels on day 7, and then decreased sharply thereafter. Cell growth increased during cultivation and reached a stable and high level of biomass after 5 days. The best fermentation conditions for resveratrol production in liquid cultures of Alternaria sp. MG1 were an inoculum size of 6 %, a medium volume of 125 mL in a 250-mL flask, a rotation speed of 101 rpm, and a temperature of 27 °C. PMID:22526800

  10. 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.

  11. 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.

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

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    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

  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. Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

    International Nuclear Information System (INIS)

    Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca2+ and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells

  15. 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

  16. Graptopetalum paraguayense and resveratrol ameliorates carboxymethyllysine (CML)-induced pancreas dysfunction and hyperglycemia.

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    Lee, Bao-Hong; Lee, Chia-Chen; Cheng, Yu-Hsiang; Chang, Wen-Chang; Hsu, Wei-Hsuan; Wu, She-Ching

    2013-12-01

    Hyperglycemia is associated with advanced glycation end products (AGEs). Recently, AGEs were found to cause pancreatic damage, oxidative stress, and hyperglycemia through the AGE receptor. Carboxymethyllysine (CML) is an AGE but whether it induces pancreatic dysfunction remains unclear. Graptopetalum paraguayense, a vegetable consumed in Taiwan, has been used in folk medicine and is an antioxidant that protects against liver damage. We investigated the protective properties of G. paraguayense 95% ethanol extracts (GPEs) against CML-induced pancreatic damage. The results indicated that resveratrol, GPE, and gallic acid (the active compound of GPE) increased insulin synthesis via upregulation of pancreatic peroxisome proliferator activated-receptor-γ (PPARγ) and pancreatic-duodenal homeobox-1 (PDX-1) but inhibited the expression of CML-mediated CCAAT/enhancer binding protein-β (C/EBPβ), a negative regulator of insulin production. Moreover, resveratrol and GPE also strongly activated nuclear factor-erythroid 2-related factor 2 (Nrf2) to attenuate oxidative stress and improve insulin sensitivity in the liver and muscle of CML-injected C57BL/6 mice and resulted in reduced blood glucose levels. Taken together, these findings suggested that GPE and gallic acid could potentially be used as a food supplement to protect against pancreatic damage and the development of diabetes. PMID:24036142

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

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    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.

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

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    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

    Science.gov (United States)

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

    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 PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, 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

  20. Effect of an antioxidant combination on the distribution of acetylcholinesterase and adenosine triphosphatase activities in the cerebellum of in lindane-intoxicated mice

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    Devendra Kumar Bhatt

    2013-04-01

    Full Text Available Objective: The present investigation ascertains a protective potential of a combination of antioxidants against lindane-induced toxicity in cerebellum of mice. Methods: For the study, animals are divided into four groups. First group is control and it is given only vehicle. Second group is treated with lindane and analysed if there are any lesions in the brain. Third group is purely antioxidants treated group; four antioxidants, i.e. resveratrol, ascorbic acid, alpha lipoic acid and vitamin E, are subcutaneously administered in a suitable combination to the animals of this group. Fourth group is treated with both lindane and antioxidants. Acetylcholinesterase (AChE and adenosine triphosphatase (ATPase activities are used as histochemical markers for manifestation of lindane-induced acute toxicity. Biochemical levels of glutathione (GSH and thiobarbituric acid reactive substances (TBARS were also evaluated for different groups to confirm the toxicity of lindane in cerebellum. Results: Treatment with lindane caused decrease in AChE and ATPase activities, and GSH levels in cerebellum whereas a significant increase was recorded in TBARS. Antioxidants treatment increased the enzymatic activities. A significant rise in GSH level was recorded in the antioxidant treatment group as compared to group I and group II whereas TBARS levels were significantly reduced. GSH and TBARS levels altered significantly in group IV as compared to control group and lindane-treated group. In group III, AChE and ATPase activities increased in layers and nuclei of cerebellum as compared to control group. Conclusions: Since the use of antioxidants prevents the inhibition of AChE and ATPase, functions which are altered due to lindane-toxicity may be protected. [J Exp Integr Med 2013; 3(2.000: 103-112

  1. Resveratrol preconditioning protects hepatocytes against hepatic ischemia reperfusion injury via Toll-like receptor 4/nuclear factor-κB signaling pathway in vitro and in vivo.

    Science.gov (United States)

    He, Diao; Guo, Zhen; Pu, Jun-Liang; Zheng, Dao-Feng; Wei, Xu-Fu; Liu, Rui; Tang, Cheng-Yong; Wu, Zhong-Jun

    2016-06-01

    The purpose of this study was to investigate the protective effect of resveratrol against hepatic ischemia reperfusion injury (HIRI) and explore the potential underlying mechanism. Resveratrol-pretreated BRL-3A (rat liver) cells and rats underwent hypoxia/reoxygenation and hepatic ischemia/reperfusion, respectively. BRL-3A cell damage was evaluated, and the mRNA and protein expression of related signal molecules was assessed in cell model. The protein expression of related signal molecules was also assessed in rat model. Inflammatory cytokines levels were determined in the cell supernatant and rat serum while rat liver function and hepatocyte apoptosis were assessed. The results revealed that resveratrol significantly enhanced cell viability, inhibited cell apoptosis, and decreased levels of lactate dehydrogenase (LDH) and production of tumor necrosis factor-α (TNF-α) and interleukin-(IL)-1β in the cell supernatant. In addition, resveratrol ameliorated elevated Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB, and the depressed inhibitor of NF-κB (IκB)-α caused by hypoxia/reoxygenation stimulation in BRL-3A cells. Moreover, resveratrol inhibited the translocation of NF-κB p65 after the stimulation of hypoxia/reoxygenation in BRL-3A cells. In vivo assays revealed that resveratrol reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and liver pathological changes, while it alleviated hepatocyte apoptosis, negatively mediated the production of TNF-α and IL-1β in serum, and reversed TLR4/NF-κB signaling pathway caused by hepatic ischemia/reperfusion stimulation in liver tissues. The results indicate that resveratrol protected hepatocytes against HIRI, which may be mediated in part via the TLR4/NF-κB signaling pathway. PMID:27064547

  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. 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

  4. Effects of resveratrol and methoxyamine on the radiosensitivity of iododeoxyuridine in U87MG glioblastoma cell line.

    Science.gov (United States)

    Khoei, Samideh; Shoja, Mohsen; Mostaar, Ahmad; Faeghi, Fariborz

    2016-06-01

    The purpose of this study was to evaluate the combination effect of resveratrol and methoxyamine on radiosensitivity of iododeoxyuridine in spheroid culture of U87MG glioblastoma cell line using colony formation and alkaline comet assays. Spheroids on day-20 with 350 µm diameters were treated with 20 µM resveratrol and/or 6 mM methoxyamine and/or 1 µM iododeoxyuridine for one volume doubling time (67 h), and then irradiated with 2 Gy gamma-radiation ((60)Co) in different groups. After treatment, viability of the cells, colony forming ability and DNA damages were obtained by blue dye exclusion, colony formation and alkaline comet assay, respectively. Our results showed that methoxyamine and resveratrol could significantly reduce colony number and induce the DNA damages of glioblastoma spheroid cells treated with iododeoxyuridine in combination with gamma-rays. Therefore, methoxyamine as base excision repair inhibitor and resveratrol as hypoxia inducible factor 1-alpha inhibitor in combination with iododeoxyuridine as radiosensitizer enhanced the radiosensitization of glioblastoma spheroid cells. PMID:26748400

  5. 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.

  6. 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

  7. A facile green approach to prepare core-shell hybrid PLGA nanoparticles for resveratrol delivery.

    Science.gov (United States)

    Kumar, Sandeep; Lather, Viney; Pandita, Deepti

    2016-03-01

    Green approach has revolutionized the area of nanoparticles (NPs) synthesis by virtue of eco and health friendly protocols. Advancing this further, the study proposes a captivating solvent free method for the preparation of green PLGA-oil nanohybrids (G-PONHs) using acrysol oil and encapsulation of resveratrol therein. G-PONHs were structurally similar to the standard PONHs, but had larger particle size of 375 nm. Avoidance of organic solvents resulted in the formation of smooth NPs which showed a considerable improvement in drug release profile and antioxidant properties. G-PONHs exhibited superior biocompatibility with normal Vero cells, while the cytotoxicity on breast cancer cells was moderate in comparison to standard NPs owing to their large size. The size of NPs was found to be a critical factor governing the amplitude of cytotoxicity. The comparative high stability of G-PONHs further favors the tremendous potential of this novel preparation method and delivery platform. PMID:26708438

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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...

  13. 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...

  14. Resveratrol as a Therapeutic Agent for Alzheimer's Disease

    OpenAIRE

    2014-01-01

    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 v...

  15. Antioxidants in Translational Medicine

    OpenAIRE

    Schmidt, Harald H.H.W.; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis; Daiber, Andreas; Cuadrado, Antonio

    2015-01-01

    Abstract Significance: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent eviden...

  16. 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...

  17. 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

  18. 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

  19. Pomegranate Seed Oil Exerts Synergistic Effects with trans-Resveratrol in a Self-nanoemulsifying Drug Delivery System.

    Science.gov (United States)

    Lu, Lu-yang; Liu, Yuan; Zhang, Zhi-feng; Gou, Xiao-jun; Jiang, Jun-hao; Zhang, Ji-zhong; Yao, Qian

    2015-01-01

    Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields. PMID:26424027

  20. 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.

  1. 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

  2. The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection

    OpenAIRE

    Kim, Seok Hwan; Park, Joo Hyun; Kim, Yu Jeong; Park, Ki Ho

    2013-01-01

    Purpose This study aimed to investigate the neuroprotective effect of resveratrol in an optic nerve transection (ONT) model and to identify the neuroprotective mechanism of resveratrol in retinal ganglion cells (RGCs). Methods ONT and retrograde labeling were performed in Sprague-Dawley rats. Various concentrations of resveratrol were injected intravitreally immediately after ONT. The number of labeled RGCs was determined at 1 and 2 weeks after ONT. The effect of resveratrol and sirtinol (a s...

  3. 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

  4. 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...

  5. 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 < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in 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

  6. 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)

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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...

  15. 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.

  16. 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...

  17. 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

  18. The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells

    International Nuclear Information System (INIS)

    Previous study reported that resveratrol has anti-tumor activity. In this study, we investigated the involvement of autophagy in the resveratrol-induced apoptotic death of human U251 glioma cells. The growth inhibition of U251 cells induced by resveratrol was assessed with methyl thiazolyl tetrazolium (MTT). The activation of autophagy and proapoptotic effect were characterized by monodansylcadaverine labeling and Hoechst stain, respectively. Mitochondrialtransmembrane potential (ΔΨm) was measured as a function of drug treatment using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). The role of autophagy and apoptosis in the resveratrol-induced death of U251 cells was assessed using autophagic and caspase inhibitors. Immunofluorescence, flow cytometry, and Western blot analysis were used to study the apoptotic and autophagic mechanisms. Methyl thiazolyl tetrazolium (MTT) assays indicated that resveratrol decreased the viability of U251 cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that resveratrol increased cell population at sub-G1 phase, an index of apoptosis. Furthermore, resveratrol-induced cell death was associated with a collapse of the mitochondrial membrane potential. The pan-caspase inhibitor Z-VAD-fmk suppressed resveratrol-induced U251 cell death. Resveratrol stimulated autophagy was evidenced by punctuate monodansylcadaverine(MDC) staining and microtubule-associated protein light chain 3 (LC3) immunoreactivty. Resveratrol also increased protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitors 3-methylademine (3-MA) and bafilomycin A1 sensitized the cytotoxicity of resveratrol. Together, these findings indicate that resveratrol induces autophagy in human U251 glioma cells and autophagy suppressed resveratrol-induced apoptosis. This study thus suggests that autophagy inhibitors can increase the cytotoxicity of resveratrol to glioma cells

  19. 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

  20. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor

    Directory of Open Access Journals (Sweden)

    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

  1. 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.

  2. 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.

  3. 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.

  4. Efflux Transport Characterization of Resveratrol Glucuronides in UDP-Glucuronosyltransferase 1A1 Transfected HeLa Cells: Application of a Cellular Pharmacokinetic Model to Decipher the Contribution of Multidrug Resistance-Associated Protein 4.

    Science.gov (United States)

    Wang, Shuai; Li, Feng; Quan, Enxi; Dong, Dong; Wu, Baojian

    2016-04-01

    Resveratrol undergoes extensive metabolism to form biologically active glucuronides in humans. However, the transport mechanisms for resveratrol glucuronides are not fully established. Here, we aimed to characterize the efflux transport of resveratrol glucuronides using UGT1A1-overexpressing HeLa cells (HeLa1A1 cells), and to determine the contribution of multidrug resistance-associated protein (MRP) 4 to cellular excretion of the glucuronides. Two glucuronide isomers [i.e., resveratrol 3-O-glucuronide (R3G) and resveratrol 4'-O-glucuronide (R4'G)] were excreted into the extracellular compartment after incubation of resveratrol (1-100 μM) with HeLa1A1 cells. The excretion rate was linearly related to the level of intracellular glucuronide, indicating that glucuronide efflux was a nonsaturable process. MK-571 (a dual inhibitor of UGT1A1 and MRPs) significantly decreased the excretion rates of R3G and R4'G while increasing their intracellular levels. Likewise, short-hairpin RNA (shRNA)-mediated silencing of MRP4 caused a significant reduction in glucuronide excretion but an elevation in glucuronide accumulation. Furthermore, β-glucuronidase expressed in the cells catalyzed the hydrolysis of the glucuronides back to the parent compound. A cellular pharmacokinetic model integrating resveratrol transport/metabolism with glucuronide hydrolysis/excretion was well fitted to the experimental data, allowing derivation of the efflux rate constant values in the absence or presence of shRNA targeting MRP4. It was found that a large percentage of glucuronide excretion (43%-46%) was attributed to MRP4. In conclusion, MRP4 participated in cellular excretion of R3G and R4'G. Integration of mechanistic pharmacokinetic modeling with transporter knockdown was a useful method to derive the contribution percentage of an exporter to overall glucuronide excretion. PMID:26758854

  5. Development and validation of an RP-HPLC method for quantification of trans-resveratrol in the plant extracts

    Directory of Open Access Journals (Sweden)

    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

  6. Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release

    Directory of Open Access Journals (Sweden)

    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.

  7. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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...

  10. 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.

  11. 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

  12. Effects of Resveratrol on Inflammatory Bowel Disease: A Review

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. New Water-Soluble Carbamate Ester Derivatives of Resveratrol

    Directory of Open Access Journals (Sweden)

    Andrea Mattarei

    2014-10-01

    Full Text Available Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of carbamate ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol-350 (mPEG-350 or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport.

  15. Antioxidant measurements.

    Science.gov (United States)

    Somogyi, Anikó; Rosta, Klára; Pusztai, Péter; Tulassay, Zsolt; Nagy, Géza

    2007-04-01

    Chemical reactions, including oxidation and reduction of molecules, occur in every cell. These reactions can lead to the production of free radicals. Free radicals react with organic substrates such as lipids, proteins, and DNA. Through oxidation free radicals cause damage to these molecules, disturbing their normal function, and may therefore contribute to a variety of diseases. The anti-oxidation system, which consists of enzymatic antioxidants and non-enzymatic antioxidants, defends against oxidative stress. The aim of this review is to summarize general aspects of methods to measure the antioxidant defence system all in one (total antioxidant capacity) and discuss a number of methods which are currently used for detection of antioxidant properties. PMID:17395989

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Antioxidant and Anti-Inflammatory Effects of Selected Natural Compounds Contained in a Dietary Supplement on Two Human Immortalized Keratinocyte Lines

    OpenAIRE

    Elena Fasano; Simona Serini; Nadia Mondella; Sonia Trombino; Leonardo Celleno; Paola Lanza; Achille Cittadini; Gabriella Calviello

    2014-01-01

    Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, α-tocopherol, and selenium) contained in a dietary supplement us...

  1. 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

  2. Resveratrol- and α-viniferin-induced alterations of acetylcholinesterase and nitric oxide synthase in Raillietina echinobothrida.

    Science.gov (United States)

    Giri, Bikash Ranjan; Roy, Bishnupada

    2015-10-01

    Phytostilbenes, like resveratrol and α-viniferin, which occur mainly in the plants and belong to the families Cyperaceae, Vitaceae, and Gnetaceae are extensively popular for their medicinal and nutritional properties. In Northeast India, the Jaintia tribes consume these phytochemicals through aqueous extract of the medicinal plant Carex baccans to control helminthiasis. The present study aimed to investigate the inhibitory effect of the phytochemicals on neurotransmitters and its related enzymes in helminth parasite Raillietina echinobothrida. Viability of the parasites exposed to the phytostilbenes and extent of inhibition of cholinergic and nitrergic enzymes were evaluated in comparison to reference anthelmintic drug praziquantel and two known enzyme inhibitors, namely Nω-nitro-L-arginine and pyridostigmine. On exposure to resveratrol, α-viniferin, and reference drug praziquantel, the parasites ceased movement at 9.37, 11.38, and 0.24 h followed by death at 23.65, 34.13, and 1.87 h, respectively. Exposed parasites also showed a significant decrease in the activity of acetylcholinesterase (46.101, 65.935, and 63.645%) and nitric oxide synthase (61.241, 55.046, and 29.618%) in comparison to the controls. In addition, a decreased trend in nitric oxide (NO) level was also detected in the tissue of different phytochemical-exposed parasites compared to control. The present study suggests that anthelmintic potential of both the phytochemicals is mediated through inhibition of two vital enzymes which play diverse role in intracellular communications through neuromuscular system. PMID:26141435

  3. 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

  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. 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...

  6. 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.

  7. Natural Antioxidants: Function and Sources

    OpenAIRE

    David Iluz; Yaron Yehoshua; Yael Kinel-Tahan; Zvy Dubinsky; Yevgenia Shebis

    2013-01-01

    The definition of antioxidants, given in 1995 by Halliwell and Gutteridge, stated that an antioxidant is “any substance that, when present at low concentrations compared with that of an oxidizable substrate, significantly delays or inhibits oxidation of that substrate” [1]. In 2007, Halliwell gave a more specific definition, stating that an antioxidant is “any substance that delays, prevents or removes oxidative damage to a target molecule” [2]. Oxidation reactions produce free radicals that ...

  8. 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.

  9. 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

  10. 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.

  11. In planta production of the highly potent resveratrol analogue pterostilbene via stilbene synthase and O-methyltransferase co-expression

    Science.gov (United States)

    Stilbenoid phytoalexins such as resveratrol, play an important defense role in several plant species against pathogens such as Botrytis cinerea. In addition to their antimicrobial properties, resveratrol and related stilbenes have also generated considerable interest as nutraceuticals, due to their...

  12. Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells

    International Nuclear Information System (INIS)

    Research highlights: → Resveratrol induces cellular senescence in glioma cell. → Resveratrol inhibits mono-ubiquitination of histone H2B at K120. → Depletion of RNF20, phenocopies the inhibitory effects of resveratrol. → Mono-ubiquitination of histone H2B at K120 is a novel target of resveratrol. → 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-β-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 senescence programs that are

  13. 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

  14. 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

  15. 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

  16. Time- and concentration-dependent effects of resveratrol in HL-60 and HepG2 cells

    DEFF Research Database (Denmark)

    Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

    2006-01-01

    Resveratrol, a phytochemical present in grapes, has been demonstrated to inhibit tumourigenesis in animal models. However, the specific mechanism by which resveratrol exerts its anticarcinogenic effect has yet to be elucidated. In the present study, the inhibitory effects of resveratrol on cell...

  17. Low-dose pterostilbene but not resveratrol is a potent neuromodulator in aging and Alzheimer’s Disease

    Science.gov (United States)

    Recent studies have implicated resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer’s Disease (AD). However, the mechanism for the favorable effects of resveratrol in the brain remains unclear and little information about direct...

  18. Effects of Resveratrol on Bone Mineral Density in Ovarectomized Rats

    OpenAIRE

    Lin, Qian; Huang, Yi-Ming; Xiao, Ben-xi; Ren, Guo-Feng

    2005-01-01

    Hormone replacement therapy (HRT) has been used to prevent osteoporosis in postmenopausal women. However, HRT is not for everyone, due to concerns of side effects as well as increased risk of breast and possibly uterine cancer. Therefore, Dietary alternatives are considered, which include Trans-3,5,4’-Trihydroxystilbene (trans-resveratrol), a phytoestrogen naturally found in grapes, peanuts and wine with beneficial effects in both cardioprotective and chemopreventive. The purpose of this stud...

  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. Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

    OpenAIRE

    Brigitte Gonthier; Nathalie Allibe; Cécile Cottet-Rousselle; Frédéric Lamarche; Laurence Nuiry; Luc Barret

    2012-01-01

    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...

  1. 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.

  2. Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

    OpenAIRE

    Montesano, A.; Luzi, L; Senesi, P.; N. Mazzocchi; Terruzzi, I

    2013-01-01

    Background Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications. Resveratrol (RSV), natural polyphenol found in grapes and in other fruits, has a plethora of health benefits in a variety of human diseases: cardio- and neuroprotection, immune regulation, cancer chemoprevention, DNA repair, prevention of mitochondrial disorder, avoidance of obesity-related diseases. In skeletal muscle, ...

  3. Antiglycation and antioxidant activities of oxyresveratrol extracted from the heartwood of Artocarpus lakoocha Roxb.

    Directory of Open Access Journals (Sweden)

    Pimporn Leelapornpisid

    2010-11-01

    Full Text Available 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.

  4. 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.

  5. 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.

  6. Preparation of resveratrol-loaded nanoporous silica materials with different structures

    International Nuclear Information System (INIS)

    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. 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.

  8. 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

  9. 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.

  10. Single-step green synthesis and characterization of gold-conjugated polyphenol nanoparticles with antioxidant and biological activities

    OpenAIRE

    Sanna, Vanna Annunziata; Pala, Nicolino; Dessì, Giuseppina; Manconi, Paola Maria; Mariani, Alberto; Dedola, Sonia; Rassu, Mauro; Crosio, Claudia; Iaccarino, Ciro; Sechi, Mario

    2014-01-01

    Background: Gold nanoparticles (GNPs) are likely to provide an attractive platform for combining a variety of biophysicochemical properties into a unified nanodevice with great therapeutic potential. In this study we investigated the capabilities of three different natural polyphenols, epigallocatechin-3-gallate (EGCG), resveratrol (RSV), and fisetin (FS), to allow synergistic chemical reduction of gold salts to GNPs and stabilization in a single-step green process. Moreover, antioxidant prop...

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

    OpenAIRE

    Matthias Riebel; Andrea Sabel; Harald Claus; Petra Fronk; Ning Xia; Huige Li; Helmut König; Heinz Decker

    2015-01-01

    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 tyrosi...

  12. INTRAHIPPOCAMPAL ADMINISTRATION OF IBOTENIC ACID INDUCED CHOLINERGIC DYSFUNCTION via NR2A/NR2B EXPRESSION: IMPLICATIONS OF RESVERATROL AGAINST ALZHEIMER DISEASE PATHOPHYSIOLOGY

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. 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. PMID:27387389

  15. 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

  16. 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors α and β in breast cancer cells.

    Science.gov (United States)

    Ronghe, Amruta; Chatterjee, Anwesha; Singh, Bhupendra; Dandawate, Prasad; Abdalla, Fatma; Bhat, Nimee K; Padhye, Subhash; Bhat, Hari K

    2016-06-15

    Breast cancer is a public health concern worldwide. Prolonged exposure to estrogens has been implicated in the development of breast neoplasms. Epidemiologic and experimental evidence suggest a chemopreventive role of phytoestrogens in breast cancers. Resveratrol, a naturally occurring phytoestrogen, has been shown to have potent anti-cancer properties. However, poor efficacy and bioavailability have prevented the use of resveratrol in clinics. In order to address these problems, we have synthesized a combinatorial library of azaresveratrol analogs and tested them for their ability to inhibit the proliferation of breast cancer cells. We have recently shown that 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD), has better anti-cancer properties than resveratrol and any other resveratrol analog we have synthesized so far. The objective of this study was to investigate the regulation of estrogen receptors (ERs) α and β by TIMBD in breast cancer cell lines. We demonstrate that TIMBD significantly induces the mRNA and protein expression levels of ERβ and inhibits that of ERα. TIMBD inhibits mRNA and protein expression levels of oncogene c-Myc, and cell cycle protein cyclin D1, which are important regulators of cellular proliferation. TIMBD significantly induces protein expression levels of tumor suppressor genes p53 and p21 in MCF-7 cells. TIMBD inhibits c-Myc in an ERβ-dependent fashion in MCF-10A and ERβ1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this analog. ERβ plays a partial role in inhibition of proliferation by TIMBD while ERα overexpression does not significantly affect TIMBD's inhibition. PMID:26970359

  17. Investigation of the potential immunomodulatory effects of resveratrol on equine whole blood: An in vitro investigation.

    Science.gov (United States)

    Martin, Lynn M; Johnson, Philip J; Amorim, Juliana R; Honaker, Allison R; Donaldson, Rebecca S; DeClue, Amy E

    2016-06-01

    Horses affected with gastrointestinal conditions such as colic or colitis are at substantial risk for translocation of bacterial components such as lipopolysaccharide (LPS, endotoxin) from the gastrointestinal tract into circulation resulting in systemic inflammation and subsequent morbidity and mortality. Therefore, there is a need for effective preventive and treatment strategies aimed at minimizing the host's inflammatory reaction to these pathogen-associated molecular patterns (PAMPs) from gastrointestinal disease. Resveratrol (RES, trans-3,5,4'-trihydroxystilbene) is a phytoalexin commonly found in fruits and beverages, including red wine. Health benefits associated with the consumption of red wine have been attributed to RES. Resveratrol has been significantly shown to exert a powerful anti-inflammatory effect in laboratory animals subjected to experimental endotoxemia/sepsis. Therefore, the objective of this study was to determine in vitro whether RES had an inhibitory effect on the production of tumor necrosis factor (TNF) in cultivated whole blood (Cwb) following stimulation by PAMPs. We hypothesized that RES would inhibit TNF production in Cwb following stimulation by LPS or lipoteichoic acid (LTA). Production of TNF bioactivity in Cwb was measured in the presence of phosphate buffered saline (control), ethanol (solvent control), dexamethasone (anti-inflammatory control), LPS, LTA, and three different concentrations of RES. Both LPS and LTA stimulated TNF production, and addition of dexamethasone was inhibitory to this effect. An anti-inflammatory effect for RES was not demonstrated under the current experimental conditions. Further studies are required to characterize the effect of RES on the equine innate immune system during systemic inflammation. PMID:27234544

  18. Impact of Dietary Antioxidants on Sport Performance: A Review.

    Science.gov (United States)

    Braakhuis, Andrea J; Hopkins, Will G

    2015-07-01

    Many athletes supplement with antioxidants in the belief this will reduce muscle damage, immune dysfunction and fatigue, and will thus improve performance, while some evidence suggests it impairs training adaptations. Here we review the effect of a range of dietary antioxidants and their effects on sport performance, including vitamin E, quercetin, resveratrol, beetroot juice, other food-derived polyphenols, spirulina and N-acetylcysteine (NAC). Older studies suggest vitamin E improves performance at altitude, with possible harmful effects on sea-level performance. Acute intake of vitamin E is worthy of further consideration, if plasma levels can be elevated sufficiently. Quercetin has a small beneficial effect for exercise of longer duration (>100 min), but it is unclear whether this benefits athletes. Resveratrol benefits trained rodents; more research is needed in athletes. Meta-analysis of beetroot juice studies has revealed that the nitrate component of beetroot juice had a substantial but unclear effect on performance when averaged across athletes, non-athletes and modes of exercise (single dose 1.4 ± 2.0%, double dose 0.5 ± 1.9%). The effect of addition of polyphenols and other components to beetroot juice was trivial but unclear (single dose 0.4 ± 3.2%, double dose -0.5 ± 3.3%). Other food-derived polyphenols indicate a range of performance outcomes from a large improvement to moderate impairment. Limited evidence suggests spirulina enhances endurance performance. Intravenous NAC improved endurance cycling performance and reduced muscle fatigue. On the basis of vitamin E and NAC studies, acute intake of antioxidants is likely to be beneficial. However, chronic intakes of most antioxidants have a harmful effect on performance. PMID:25790792

  19. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice.

    Science.gov (United States)

    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

  20. Resveratrol and health from a consumer perspective: perception, attitude, and adoption of a new functional ingredient.

    Science.gov (United States)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-08-01

    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 resveratrol consumer studies with Danish and U.S. consumers to look at current findings and future research directions for three questions. (1) Which factors determine consumer interest in a yet unknown functional ingredient such as resveratrol? (2) How should resveratrol be marketed as a new functional ingredient to be understood and favorably perceived? (3) What could be the effects of adoption of an ingredient such as resveratrol on the healthy lifestyle of a consumer? Literature and first results indicate that personal relevance and familiarity are crucial factors; however, consumers show little 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 to more favorable attitudes in Danish 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. PMID:26315295

  1. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Directory of Open Access Journals (Sweden)

    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 polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT. Resveratrol (18 mg/kg/day; HS-RSV was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition. Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001, and prevented the 25% reduction in body weight in HS-NT (P<0.001. Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  2. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Science.gov (United States)

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  3. TRENDS ON ANALYTICAL METHODS FOR RESVERATROL, A MAJOR BIOACTIVE

    OpenAIRE

    Cabrita, Maria João; Martins, Nuno; Soares, Bruno; Costa Freitas, Ana Maria; Garcia, Raquel

    2014-01-01

    Resveratrol (3,5,4-trans-trihydroxystilbene) is a member of the stilbene group of phenolic compounds, comprising two aromatic rings linked by an ethylene bridge and is considered one of the most promising bioactive compounds due to its bioactivity. Wine is one of the main source of this bioactive compound in Mediterranean diet. Several authors have dedicated their research to the relationship between diet and health, and concerning wine and health studies, ‘‘French Paradox’’ was the starting ...

  4. Resveratrol attenuates CoCl2-induced cochlear hair cell damage through upregulation of Sirtuin1 and NF-κB deacetylation.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available The goals of this study were to investigate the effects of hypoxia on cochlear hair cell damage, and to explore the role of sirtuin1 in hypoxia-induced hair cell damage. Cochlear organotypic cultures from postnatal day 4 rats were used in this study. Hypoxia was induced by treating cochlear explants with CoCl2. Cochlear cultures were treated with CoCl2 alone or in combination with the sirtuin1 activator resveratrol and the sirtuin1 inhibitor sirtinol. Hair cell damage was identified by phalloidin staining and imaged using scanning electron microscopy. RT-PCR and Western blot analyses were used to detect the expression of sirtuin1 and acetylated nuclear factor-κB (NF-κB. Low concentrations of CoCl2 (100-200 μM did not cause an obvious change in the number and morphology of hair cells, whereas higher concentrations of CoCl2 (300-400 μM induced swelling of hair cells, accompanied by cell loss. Increased sirtuin1 expression was induced by CoCl2 at 100 to 200 μM, but not at 400 μM. NF-κB acetylation was significantly increased in explants treated with 400 μM CoCl2. Pretreatment with resveratrol prevented CoCl2-induced hair cell loss and acetylation of NF-κB. The protective effect of resveratrol was significantly reduced by sirtinol. CoCl2 induces hair cell damage in organotypic cochleae cultures. Resveratrol attenuates CoCl2-induced cochlear hair cell damage possibly via activation of sirtuin1, which deacetylates NF-κB.

  5. Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol

    Science.gov (United States)

    Medina-Aguilar, Rubiceli; Pérez-Plasencia, Carlos; Marchat, Laurence A.; Gariglio, Patricio; García Mena, Jaime; Rodríguez Cuevas, Sergio; Ruíz-García, Erika; Astudillo-de la Vega, Horacio; Hernández Juárez, Jennifer; Flores-Pérez, Ali; López-Camarillo, César

    2016-01-01

    Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization. PMID:27355345

  6. The potential role of antioxidants in metabolic syndrome.

    Science.gov (United States)

    Gregório, Bianca Martins; De Souza, Diogo Benchimol; de Morais Nascimento, Fernanda Amorim; Pereira, Leonardo Matta; Fernandes-Santos, Caroline

    2016-01-01

    Metabolic syndrome (MS) is a constellation of risk factors that raise the risk for heart disease and other health problems, such as obesity. The clustering of metabolic abnormality is closely related to oxidative stress and inflammation, as well as the progression of atherosclerosis. Antioxidants are reducing agents which inhibit the oxidation of other molecules and can be used not only to prevent but also to treat health complications of MS and atherosclerosis. They can be ingested in the normal diet, since they are found in many food sources, or in supplement formulations. Herein, we aim to review the literature concerning the effect of antioxidants on MS. We focus on antioxidants with some evidence of action on this condition, like flavonoids, arginine, vitamin C, vitamin E, carotenoids, resveratrol and selenium. Experimental and clinical studies show that most of the above-mentioned antioxidants exhibit a wide range of effects in protecting the human body, especially in MS patients. However, the underlying mechanisms are not fully elucidated for most of these compounds. Also, some of them should be used with caution because their excess can be toxic to the body. In general, antioxidants (especially those present in foods) can be used by MS individuals because of their direct effect on oxidative stress. Additionally, they should be encouraged as part of a nutritional lifestyle change, since this is part of the therapy for all diseases involved in metabolic disorders. PMID:26648468

  7. Comparison of Antagonism of Grape Juice and Resveratrol to Oxidative Damage Induced by Cadmium in Mice%葡萄汁与白黎芦醇对镉染毒小鼠抗氧化损伤作用的比较

    Institute of Scientific and Technical Information of China (English)

    庞雅琴; 周敏; 庞广福; 郑子敏; 韦健全

    2011-01-01

    Objective To compare the effects of grape juice and resveratrol on antioxidation and promoting cadmium(Cd) excretion in mice exposed to Cd and the mechanism. Methods Thirty-two 5 weeks old Kunming mice were randomly divided into 4 groups, namely normal group (treated with dd H2O), CdCl2 (50 mg/L) group, grape juice ( containing resveratrol 65 pμg/ml) plus CdC12 group, resveratrol (65 μg/ml) plus CdCl2 treated group, 8 mice in each group. The mice were treated with CdCl2 through drinking water, and treated with the grape juice and resveratrol through gavage with 0.02 ml/g, once a day for 4 consecutive weeks.In the end of treatment, the Cd levels in liver and kidney,the activity of alanine aminotranferase (ALT) and the content of ureanitrogen(BUN) in serum were measured, and the activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px), the content of malony diadehyde (MDA) in serum,liver and kidney were measured respectively. Results Compared with the CdCl2 treated group, the Cd levels in liver and kidney ,the serum level of ALT and BUN, the contents of MDA in serum, liver and kidney in grape juice plus CdCl2 treated group and resveratrol plus CdCl2 group decreased while the activities of SOD and GSH-Px in serum, liver and kidney increased significantly(P<0.01 ). Compared with resveratrol plus CdC12 treated group, the Cd levels in liver and kidney,the serum level of ALT and BUN,the contents of MDA in serum,liver and kidney in grape juice plus CdCl2 group decreased while the activities of SOD and GSH-Px in serum, kidney and the activities of SOD in liver increased significantly (P< 0.01 ). Conclusion Grape juice has protective effect on the damage of liver and kidney of mice induced by Cd and has stronger effect of promote Cd excretion compared with resveratrol.%目的 比较葡萄汁与单体白黎芦醇对镉染毒小鼠的抗氧化损伤作用和促排镉作用及其作用机制.方法 将32只5周龄清洁级昆明小鼠随机分为4组,

  8. Resveratrol prevents interleukin-1β-induced dysfunction of pancreatic β-cells ☆

    OpenAIRE

    Chen, Fang; Zhou, Xiaohua; Lin, Yan; JING, CHANGWEN; Yang, Tao; Ji, Yong; Sun, Yujie; Han, Xiao

    2010-01-01

    Objective Interleukin-1β (IL-1β) plays an important role in the development of type 1 and type 2 diabetes mellitus. Resveratrol, a polyphenol, is known to have a wide range of pharmacological properties in vitro. In this research, we examined the effects of resveratrol on IL-1β-induced β-cell dysfunction. Methods We first evaluated the effect of resveratrol on nitric oxide (NO) formation in RINm5F cells stimulated with IL-1β using the Griess method. Next, we performed transient transfection a...

  9. 白藜芦醇对动物表观遗传学调控的作用机制%The Mechanism of Resveratrol in Epigenetics Regulation in Animals

    Institute of Scientific and Technical Information of China (English)

    张卫兵; 张蓉; 屠焰; 刁其玉

    2016-01-01

    Resveratrol is a kind of non⁃flavonoid phenolic compounds, and is a kind of natural plant anti⁃toxin, which widely exists in many plants. Resveratrol has various bioactivities and pharmacological effects, such as antioxidant activity, anticancer activity, neuroprotective activity, cardioprotective capacity and anti⁃aging activ⁃ity. Recent studies indicated that these activities were largely accomplished by epigenetic modifications in the regulation of gene expression. In this paper, we summarized the main mechanism of epigenetic modification and the research progress of resveratrol in animals and humans gene DNA methylation, histone acetylation and miRNA. From the aspects of epigenetic modification, we reviewed the pathway of resveratrol in animals and humans.%白藜芦醇是一种非黄酮类多酚物质,也是一种天然的植物抗毒素,广泛存在于多种植物中。白藜芦醇具有多种生物活性和药理作用,如抗氧化、抗肿瘤、神经及心血管保护和抗衰老等作用。新近研究表明白藜芦醇的这些作用与表观遗传学修饰调控基因的内在表达密切相关。本文总结了表观遗传学主要修饰机制以及白藜芦醇参与动物和人基因DNA甲基化、组蛋白乙酰化、微小RNA等方面的研究进展,从表观遗传学修饰水平方面综述了白藜芦醇在动物和人体内发挥作用的途径。

  10. Study of leaf metabolome modifications induced by UV-C radiations in representative Vitis, Cissus and Cannabis species by LC-MS based metabolomics and antioxidant assays.

    Science.gov (United States)

    Marti, Guillaume; Schnee, Sylvain; Andrey, Yannis; Simoes-Pires, Claudia; Carrupt, Pierre-Alain; Wolfender, Jean-Luc; Gindro, Katia

    2014-01-01

    UV-C radiation is known to induce metabolic modifications in plants, particularly to secondary metabolite biosynthesis. To assess these modifications from a global and untargeted perspective, the effects of the UV-C radiation of the leaves of three different model plant species, Cissus antarctica Vent. (Vitaceae), Vitis vinifera L. (Vitaceae) and Cannabis sativa L. (Cannabaceae), were evaluated by an LC-HRMS-based metabolomic approach. The approach enabled the detection of significant metabolite modifications in the three species studied. For all species, clear modifications of phenylpropanoid metabolism were detected that led to an increased level of stilbene derivatives. Interestingly, resveratrol and piceid levels were strongly induced by the UV-C treatment of C. antarctica leaves. In contrast, both flavonoids and stilbene polymers were upregulated in UV-C-treated Vitis leaves. In Cannabis, important changes in cinnamic acid amides and stilbene-related compounds were also detected. Overall, our results highlighted phytoalexin induction upon UV-C radiation. To evaluate whether UV-C stress radiation could enhance the biosynthesis of bioactive compounds, the antioxidant activity of extracts from control and UV-C-treated leaves was measured. The results showed increased antioxidant activity in UV-C-treated V. vinifera extracts. PMID:25197936

  11. Study of Leaf Metabolome Modifications Induced by UV-C Radiations in Representative Vitis, Cissus and Cannabis Species by LC-MS Based Metabolomics and Antioxidant Assays

    Directory of Open Access Journals (Sweden)

    Guillaume Marti

    2014-09-01

    Full Text Available UV-C radiation is known to induce metabolic modifications in plants, particularly to secondary metabolite biosynthesis. To assess these modifications from a global and untargeted perspective, the effects of the UV-C radiation of the leaves of three different model plant species, Cissus antarctica Vent. (Vitaceae, Vitis vinifera L. (Vitaceae and Cannabis sativa L. (Cannabaceae, were evaluated by an LC-HRMS-based metabolomic approach. The approach enabled the detection of significant metabolite modifications in the three species studied. For all species, clear modifications of phenylpropanoid metabolism were detected that led to an increased level of stilbene derivatives. Interestingly, resveratrol and piceid levels were strongly induced by the UV-C treatment of C. antarctica leaves. In contrast, both flavonoids and stilbene polymers were upregulated in UV-C-treated Vitis leaves. In Cannabis, important changes in cinnamic acid amides and stilbene-related compounds were also detected. Overall, our results highlighted phytoalexin induction upon UV-C radiation. To evaluate whether UV-C stress radiation could enhance the biosynthesis of bioactive compounds, the antioxidant activity of extracts from control and UV-C-treated leaves was measured. The results showed increased antioxidant activity in UV-C-treated V. vinifera extracts.

  12. Efficacy and Tolerability of a Skin Brightening/Anti-Aging Cosmeceutical Containing Retinol 0.5%, Niacinamide, Hexylresorcinol, and Resveratrol.

    Science.gov (United States)

    Farris, Patricia; Zeichner, Joshua; Berson, Diane

    2016-07-01

    Consumers are increasingly interested in over-the-counter skin care products that can improve the appearance of photodamaged and aging skin. This 10-week, open-label, single- center study enrolled 25 subjects with mild to moderate hyperpigmentation and other clinical stigmata of cutaneous aging including fine lines, sallowness, lack of clarity, and wrinkling. Their mean age was 53.4±7.7 years. The test product contained retinol 0.5% in combination with niacinamide 4.4%, resveratrol 1%, and hexylresorcinol 1.1% in a moisturizing base. Subjects were provided a skin care regimen including a cleanser, hydrating serum, moisturizer, and an SPF 30 sunscreen for daily use. The test product was applied only at night. The use of this skin brightening/anti-aging cosmeceutical was found to provide statistically significant improvements in all efficacy endpoints by study end. Fine lines, radiance, and smoothness were significantly improved as early as week 2 (P The results of this open-label clinical study suggest that a topical cream containing retinol 0.5% in combination with niacinamide, resveratrol, and hexylresorcinol is efficacious and tolerable for skin brightening/anti-aging when used with a complementary skin care regimen including SPF 30 sun protection. J Drugs Dermatol. 2016;15(7):863-868. PMID:27391637

  13. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects.

    Science.gov (United States)

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes; Rozell, Björn; Eriksson, Maria

    2015-08-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that is most commonly caused by a de novo point mutation in exon 11 of the LMNA gene, c.1824C>T, which results in an increased production of a truncated form of lamin A known as progerin. In this study, we used a mouse 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 progerin splicing give hope to patients who are affected by HGPS. PMID:25877214

  14. Antioxidative defense

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar, to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.

  15. The resveratrol-enriched rice DJ526 boosts motor coordination and physical strength.

    Science.gov (United States)

    Chung, Hea-Jong; Sharma, Satya Priya; Kim, Hyeon-Jin; Baek, So-Hyeon; Hong, Seong-Tshool

    2016-01-01

    The main objective of current genetic modifications in crops is to boost agricultural production or to develop GM crops with an improved nutrient profile by introducing a new trait to the plants. A GM crop surpassing the ability of the introduced genetic characteristics has not been developed yet. Here, we show that the resveratrol-enriched rice DJ526, a GM crop, has unexpectedly high beneficial health effects surpassing the introduced genetic characteristic of resveratrol synthetic ability. The synergistic effect of its innate and transgenic properties not only ameliorates age-related deterioration but also boosts motor coordination and physical strength during the aging process. The gene expression profiling analyses by DNA chip showed that the gene expression pattern of mice fed resveratrol-enriched rice DJ526 was very different from mice fed either resveratrol or Dongjin rice alone, respectively, modifying expression of genes related to aging regulation, cell differentiation, extracellular matrix, neurogenesis, or secretion. PMID:27044601

  16. The role of resveratrol in the regulation of cell metabolism – a review

    Directory of Open Access Journals (Sweden)

    Marek Pieszka

    2016-02-01

    Full Text Available Moderate wine drinking is associated with reduced risk of cardiovascular, cerebrovascular and peripheral vascular disease, and reduced risk of cancer. This phenomenon is called the “French paradox”, since it was observed for the first time in France – a country famous for its wine production. In the literature, the cardioprotective effect of wine is very well described and attributed mainly to contained therein resveratrol. Recently, it has been demonstrated that resveratrol extends the lifespan of yeast through activation of the SirT1 longevity gene, which is also responsible for the longevity caused by caloric restriction. Furthermore, resveratrol exhibits high biological activity, affecting cell structures and contributing to their protection. This paper summarizes the available reports on functional and molecular aspects of resveratrol, wines and grapes as a result of the activation of longevity genes.

  17. Resveratrol modulates the angiogenic response to exercise training in skeletal muscle of aged men

    DEFF Research Database (Denmark)

    Gliemann Hybholt, Lasse; Olesen, Jesper; Biensø, Rasmus S;

    2014-01-01

    Aim: The polyphenol resveratrol has in animal studies been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Methods: Forty-three healthy...... physically inactive aged men (65±1 years) were divided into A) a training group that conducted 8 weeks of intense exercise training where half of the subjects received a daily intake of either 250 mg trans resveratrol (n=14) and the other half received placebo (n=13); and B) a non-training group that...... show that exercise training has a strong angiogenic effect whereas resveratrol supplementation may limit basal and training-induced angiogenesis....

  18. [The role of resveratrol in the regulation of cell metabolism--a review].

    Science.gov (United States)

    Pieszka, Marek; Szczurek, Paulina; Ropka-Molik, Katarzyna; Oczkowicz, Maria; Pieszka, Magdalena

    2016-01-01

    Moderate wine drinking is associated with reduced risk of cardiovascular, cerebrovascular and peripheral vascular disease, and reduced risk of cancer. This phenomenon is called the "French paradox", since it was observed for the first time in France--a country famous for its wine production. In the literature, the cardioprotective effect of wine is very well described and attributed mainly to contained therein resveratrol. Recently, it has been demonstrated that resveratrol extends the lifespan of yeast through activation of the SirT1 longevity gene, which is also responsible for the longevity caused by caloric restriction. Furthermore, resveratrol exhibits high biological activity, affecting cell structures and contributing to their protection. This paper summarizes the available reports on functional and molecular aspects of resveratrol, wines and grapes as a result of the activation of longevity genes. PMID:26943309

  19. In vitro evaluation of the antioxidant, 3,5-dihydroxy-4-ethyl-trans-stilbene (DETS isolated from Bacillus cereus as a potent candidate against malignant melanoma

    Directory of Open Access Journals (Sweden)

    Mohandas eC

    2016-04-01

    Full Text Available 3,5-dihydroxy-4-ethyl-trans-stilbene (DETS is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2− scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity towards five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans-3,4,5-trihydroxystilbene, a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity towards the human melanoma cell line, A375 (IC50: 24.01 μM followed by cervical [HeLa- 46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM. In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity

  20. Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro

    Institute of Scientific and Technical Information of China (English)

    Long-De Wang; Xiao-Qing Qiu; Zhi-Feng Tian; Ying-Fu Zhang; Hong-Fang Li

    2008-01-01

    AIM:To observe and compare the effects of phytoestrogen genistein,resveratrol and 17β-estradiol on the tonic contraction and the phasic contraction of isolated gallbladder muscle strips and to study the underlying mechanisms.METHODS:Isolated strips of gallbladder muscle from guinea pigs were suspended in organ baths containing Kreb's solution,and the contractilities of strips were measured before and after incubation with genistein,resveratrol and 17β-estradiol respectively.RESULTS:Similar to 17β-estradiol,genistein and resveratrol could dose-dependently inhibit the phasic contractile activities,they decreased the mean contractlie amplitude and the contractlie frequencies of gallbladder muscle strips,and also produced a marked reduction in resting tone.The blocker of estrogen receptor ICI 182780 failed to alter the inhibitory effects induced by genistein and resveratrol,but potassium bisperoxo(1,10 phenanthroline)oxovanadate bpV(phen),a potent protein tyrosine phosphatase inhibitor,markedly attenuated the inhibitory effects induced by genistein and resveratrol.In calcium-free Kreb's solution containing 0.01 mmol/L egtazic acid(EGTA),genistein and resveratrol inhibited the first phasic contraction induced by acetylcholine(Ach),but did not affect the second contraction induced by CaCl2.In addition,genistein,resveratrol and 17β-estradiol also could reduce the contractile responses of Ach and KCI,and shift their cumulative concentration-response curves rightward.CONCLUSION:Phytoestrogen genistein and resveratrol can directly inhibit the contractile activity of isolated gallbladder muscle both at rest and in response to stimulation.The mechanisms responsible for the inhibitory effects probably due mainly to inhibition of tyrosine kinase,Ca2+ influx through potential-dependent calcium channels(PDCs)and Ca2+ release from sarcoplasmic reticulum(SR),but were not related to the estrogen receptors.

  1. Evaluating the Effect of Expressing a Peanut Resveratrol Synthase Gene in Rice

    Science.gov (United States)

    Li, Zhen; Wang, Qingguo; Yao, Fangyin; Yang, Lianqun; Pan, Jiaowen; Liu, Wei

    2015-01-01

    Resveratrol (Res) is a type of natural plant stilbenes and phytoalexins that only exists in a few plant species. Studies have shown that the Res could be biosynthesized and accumulated within plants, once the complete metabolic pathway and related enzymes, such as the key enzyme resveratrol synthase (RS), existed. In this study, a RS gene named PNRS1 was cloned from the peanut, and the activity was confirmed in E. coli. Using transgenic approach, the PNRS1 transgenic rice was obtained. In T3 generation, the Res production and accumulation were further detected by HPLC. Our data revealed that compared to the wild type rice which trans-resveratrol was undetectable, in transgenic rice, the trans-resveratrol could be synthesized and achieved up to 0.697 μg/g FW in seedlings and 3.053 μg/g DW in seeds. Furthermore, the concentration of trans-resveratrol in transgenic rice seedlings could be induced up to eight or four-fold higher by ultraviolet (UV-C) or dark, respectively. Simultaneously, the endogenous increased of Res also showed the advantages in protecting the host plant from UV-C caused damage or dark-induced senescence. Our data indicated that Res was involved in host-defense responses against environmental stresses in transgenic rice. Here the results describes the processes of a peanut resveratrol synthase gene transformed into rice, and the detection of trans-resveratrol in transgenic rice, and the role of trans-resveratrol as a phytoalexin in transgenic rice when treated by UV-C and dark. These findings present new outcomes of transgenic approaches for functional genes and their corresponding physiological functions, and shed some light on broadening available resources of Res, nutritional improvement of crops, and new variety cultivation by genetic engineering. PMID:26302213

  2. Evaluating the Effect of Expressing a Peanut Resveratrol Synthase Gene in Rice.

    Directory of Open Access Journals (Sweden)

    Shigang Zheng

    Full Text Available Resveratrol (Res is a type of natural plant stilbenes and phytoalexins that only exists in a few plant species. Studies have shown that the Res could be biosynthesized and accumulated within plants, once the complete metabolic pathway and related enzymes, such as the key enzyme resveratrol synthase (RS, existed. In this study, a RS gene named PNRS1 was cloned from the peanut, and the activity was confirmed in E. coli. Using transgenic approach, the PNRS1 transgenic rice was obtained. In T3 generation, the Res production and accumulation were further detected by HPLC. Our data revealed that compared to the wild type rice which trans-resveratrol was undetectable, in transgenic rice, the trans-resveratrol could be synthesized and achieved up to 0.697 μg/g FW in seedlings and 3.053 μg/g DW in seeds. Furthermore, the concentration of trans-resveratrol in transgenic rice seedlings could be induced up to eight or four-fold higher by ultraviolet (UV-C or dark, respectively. Simultaneously, the endogenous increased of Res also showed the advantages in protecting the host plant from UV-C caused damage or dark-induced senescence. Our data indicated that Res was involved in host-defense responses against environmental stresses in transgenic rice. Here the results describes the processes of a peanut resveratrol synthase gene transformed into rice, and the detection of trans-resveratrol in transgenic rice, and the role of trans-resveratrol as a phytoalexin in transgenic rice when treated by UV-C and dark. These findings present new outcomes of transgenic approaches for functional genes and their corresponding physiological functions, and shed some light on broadening available resources of Res, nutritional improvement of crops, and new variety cultivation by genetic engineering.

  3. Protection of Bovine Mammary Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Cell Damage by Resveratrol

    OpenAIRE

    Xiaolu Jin; Kai Wang; Hongyun Liu; Fuliang Hu; Fengqi Zhao; Jianxin Liu

    2016-01-01

    The mammary epithelial cells (MECs) of high-producing dairy cows are likely to be subject to oxidative stress (OS) due to the intensive cell metabolism. The objectives of this study were to investigate the cytoprotective effects of resveratrol against hydrogen peroxide- (H2O2-) induced OS in cultured bovine MECs (MAC-T). Pretreatment of MAC-T cells with resveratrol could rescue the decrease in cell viability and resulted in lower intracellular reactive oxygen species (ROS) accumulation after ...

  4. Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release

    OpenAIRE

    Feng Zhang; Yan-Ying Wang; Hang Liu; Yuan-Fu Lu; Qin Wu; Jie Liu; Jing-Shan Shi

    2012-01-01

    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 c...

  5. Resveratrol: therapeutic role in metabolic and reproductive function in obese broodmares

    OpenAIRE

    Kohlhaas, Kaylee Shevon

    2013-01-01

    Resveratrol, a naturally-occurring phytoestrogenic stilbene derivative, has been shown to elicit shifts in physiology of obese animals consuming a high calorie or ad libitum diet toward that of lean counterparts. This study was designed to evaluate effects of oral resveratrol supplementation on parameters of metabolic health and reproductive cyclicity in obese mares on pasture. Seventeen healthy, mares were matched by age and assigned to obese control (OBC; n=5, mean BCS=7.4±0.3), obese suppl...

  6. Protective action of resveratrol in human skin: possible involvement of specific receptor binding sites.

    Directory of Open Access Journals (Sweden)

    Stéphane Bastianetto

    Full Text Available 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 AND FINDINGS: Using human skin tissue, we report here the presence of specific [(3H]-resveratrol binding sites (K(D  =  180 nM that are mainly located in the epidermis. Exposure of HaCaT cells to the nitric oxide free radical donor sodium nitroprusside (SNP; 0.3-3 mM resulted in cell death which was reduced by resveratrol (EC(50  =  14.7 µM, and to a much lesser extent by the resveratrol analogue piceatannol (EC(50  =  95 µM and epigallocatechin gallate (EC(50  =  200 µM, a green-tea derived polyphenol. The protective action of resveratrol likely relates to its anti-apoptotic effect since at the same range of concentration it was able to reduce both the number of apoptotic cells as well as mitochondrial apoptotic events triggered by SNP. CONCLUSION: Taken together, these findings suggest that resveratrol, by acting on specific polyphenol binding sites in epidermis, may be useful to prevent skin disorders associated with aging.

  7. Resveratrol Induces Vascular Smooth Muscle Cell Differentiation through Stimulation of SirT1 and AMPK

    OpenAIRE

    Anne Marie Thompson; Martin, Kathleen A.; Rzucidlo, Eva M.

    2014-01-01

    Phenotypic plasticity in vascular smooth muscle cells (VSMC) is necessary for vessel maintenance, repair and adaptation to vascular changes associated with aging. De-differentiated VSMC contribute to pathologies including atherosclerosis and intimal hyperplasia. As resveratrol has been reported to have cardio- protective effects, we investigated its role in VSMC phenotypic modulation. We demonstrated the novel finding that resveratrol promoted VSMC differentiation as measured by contractile p...

  8. Molekulare Mechanismen der antiproliferativen Wirkung sekundärer Pflanzeninhaltsstoffe am Beispiel von Resveratrol

    OpenAIRE

    Wolter, Freya

    2002-01-01

    Das pflanzliche Polyphenol Resveratrol, kommt unter anderem in Rotwein, Weintrauben und Erdnüssen vor und wirkt chemopräventiv. Ziel der vorliegenden Arbeit war es, die molekularen Mechanismen der Wachstumshemmung durch Resveratrol auf kolorektale Karzinomzellen zu charakterisieren. Zellkultur: HCT-116 und Caco-2 (kolorektale Karzinomzelllinien) Zytotoxizität: Laktatdehydrogenasemessung im Überstand Zellzahl: Kristallviolettfärbung Proliferation: [3H]-Thymidin- bzw. [14C]-Leucinei...

  9. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults

    OpenAIRE

    Witte, V; Kerti, L.; Margulies, D; Flöel, A.

    2014-01-01

    Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanisms underlying this effect. Twenty-three healthy overweight older individua...

  10. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases

    OpenAIRE

    Park Sung-Jun; Ahmad Faiyaz; Philp Andrew; Baar Keith; Williams Tishan; Luo Haibin; Ke Hengming; Rehmann Holger; Taussig Ronald; Brown Alexandra L; Kim Myung K; Beaven Michael A; Burgin Alex B; Manganiello Vincent; Chung Jay H

    2012-01-01

    Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2...

  11. The sources of natural antioxidants

    OpenAIRE

    Elżbieta Sikora; Ewa Cieślik; Kinga Topolska

    2008-01-01

    Intensive oxidative processes occuring in human organism lead to formation of oxygen reactive forms, which can damage systemic cells and tissues. It is shown, that body endogenous protective system can be supported in that case by natural antioxidant compounds provided from food. The assessment of food products as the potential sources of antioxidants was performed, taking into consideration the kinds of compounds supplied, and their significance in the diet of different nations.

  12. The sources of natural antioxidants

    Directory of Open Access Journals (Sweden)

    Elżbieta Sikora

    2008-03-01

    Full Text Available Intensive oxidative processes occuring in human organism lead to formation of oxygen reactive forms, which can damage systemic cells and tissues. It is shown, that body endogenous protective system can be supported in that case by natural antioxidant compounds provided from food. The assessment of food products as the potential sources of antioxidants was performed, taking into consideration the kinds of compounds supplied, and their significance in the diet of different nations.

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

    OpenAIRE

    Gambini, J.; Inglés, M.; G. Olaso; Lopez-Grueso, R.; Bonet-Costa, V.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K. M.; Gomez-Cabrera, M. C.; Vina, J.; C. Borras

    2015-01-01

    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 acti...

  14. Inhibitory Effects of Resveratrol on Melanin Synthesis in Ultraviolet B-Induced Pigmentation in Guinea Pig Skin

    OpenAIRE

    Lee, Taek Hwan; Seo, Jae Ok; Baek, So-Hyeon; KIM, Sun Yeou

    2014-01-01

    Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits α-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentati...

  15. A positive feedback pathway of estrogen biosynthesis in breast cancer cells is contained by resveratrol

    International Nuclear Information System (INIS)

    Cytochrome P450 (CYP) 19 enzyme or aromatase catalyses the rate-determining step of estrogen synthesis. The transcriptional control of CYP19 gene is highly specific in different cell types, for instance, Promoter I.3/II is commonly used for regulation in breast cancer cells. Recently, a positive feedback pathway for estrogen synthesis has been identified in ERα expressing SK-BR-3 cells. CYP19 mRNA abundance and activity are increased in this pathway and the promoter usage is switched from Promoter I.3/II to I.1 through a non-genomic process. In the present study, effect of the phytocompound resveratrol on this Promoter I.1-controlled expression of aromatase was investigated. Results indicated that resveratrol reduced the estradiol-induced mRNA abundance in SK-BR-3 cells expressing ERα. Luciferase reporter gene assays revealed that resveratrol could also repress the transcriptional control dictated by Promoter I.1. Since the ERE-driven luciferase activity was not repressed by resveratrol, the nuclear events of estrogen were unlikely to be suppressed by resveratrol. Instead the phytochemical reduced the amount of ERK activated by estradiol, which could be the pathway responsible for Promoter I.1 transactivation and the induced CYP19 expression. The present study illustrated that resveratrol impeded the non-genomic induction of estrogen on CYP19

  16. Structural determinants of resveratrol for cell proliferation inhibition potency: experimental and docking studies of new analogs.

    Science.gov (United States)

    Mazué, Frédéric; Colin, Didier; Gobbo, Jessica; Wegner, Maria; Rescifina, Antonio; Spatafora, Carmela; Fasseur, Dominique; Delmas, Dominique; Meunier, Philippe; Tringali, Corrado; Latruffe, Norbert

    2010-07-01

    Resveratrol is the subject of intense research because of the abundance of this compound in the human diet and as one of the most valuable natural chemopreventive agents. Further advances require new resveratrol analogs be used to identify the structural determinants of resveratrol for the inhibition potency of cell proliferation by comparing experimental and docking studies. Therefore, we synthesized new trans/(E)- and cis/(Z)-resveratrol - analogs not reported to date - by modifying the hydroxylation pattern of resveratrol and a double bond geometry. We included them in a larger panel of 14 molecules, including (Z)-3,5,4'-trimethoxystilbene, the most powerful molecule that is used as reference. Using a docking model complementary to experimental studies on the proliferation inhibition of the human colorectal tumor SW480 cell line, we show that methylation is the determinant substitution in inhibition efficacy, but only in molecules bearing a Z configuration. Most of the synthetic methylated derivatives (E or Z) stop mitosis at the M phase and lead to polyploid cells, while (E)-resveratrol inhibits cells at the S phase. Docking studies show that almost all of the docked structures of (Z)-polymethoxy isomers, but not most of the (E)-polymethoxy isomers substantially overlap the docked structure of combretastatin A-4, taken as reference ligand at the colchicine-tubulin binding site. PMID:20395019

  17. STUDY ON LIQUID-LIQUID EXTRACTION OF RESVERATROL FROM GIANT KNOTWEED AND ITS PROTECTIVE EFFECT ON MYOCARDIUM INJURY

    Institute of Scientific and Technical Information of China (English)

    唐玉海; 刘芸; 黄伟; 刘宏浪

    2002-01-01

    Objective An efficient extraction and separation method of resveratrol from a Chinese herb giant knotweed was developed and the protective effect of resveratrol on myocardium injury was investigated.Methods An orthogonal experiment was utilized to optimize the extraction conditions and the pure white crystal obtained utilizing the proposed method was used for the investigation of myocardium ischemic injury.Results Resveratrol was found to have many beneficial activities including the protective effect on the heart and the scavenging of free radical.Conclusion The protective effect of resveratrol on myocardium injury is related to the quenching of lipid peroxidation.

  18. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model

    Science.gov (United States)

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

  19. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model.

    Science.gov (United States)

    Xu, Meng; Xue, Wanli; Ma, Zhenhua; Bai, Jigang; Wu, Shengli

    2016-01-01

    Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200-300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both p euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all p < 0.001), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. PMID:27433290

  20. Green Tea and Its Antioxidant Properties

    OpenAIRE

    Yeh, Jason

    1999-01-01

    Green tea contains antioxidants which have been implicated to contribute to reduced risk of cardiovascular disease. This may be explained in part by the green tea's antioxidant properties. Green tea is a rich source of flavonoids with high antioxidant activity both in vitro and in vivo. This includes the ability of green tea to lower the oxidizability of low-density lipoprotein (LDL) in vitro. In vivo lipid oxidation as measure by plasma lipid peroxides and LDL oxidizability are significantly...

  1. A novel monolithic controlled delivery system of resveratrol for enhanced hepatoprotection: nanoformulation development, pharmacokinetics and pharmacodynamics.

    Science.gov (United States)

    Singh, Anjali; Ahmad, Iqbal; Ahmad, Sayeed; Iqbal, Zeenat; Ahmad, Farhan J

    2016-09-01

    The current investigation aims to present a novel solid lipid-based nanoparticulate system of resveratrol (RV) for the effective treatment of liver cirrhosis. A simplified solvent injection method was employed and the Box-Behnken experimental design was applied for optimization to get a window particle size of 150-200 nm having maximum entrapment efficiency as well as % release. Optimized resveratrol solid lipid nanoparticles (RV-SLNs) (SR-1) of appropriate characteristics (particle size = 191.1 ± 10.44 nm; zeta potential= -13.56 ± 4.14 mV; entrapment efficiency = 75.23 ± 3.85%; maximum % release = 80.53 ± 3.99%) were produced. Differential scanning calorimetry and X-ray diffraction studies were carried out which collectively proved the reduced crystallinity and stability enhancing the effect of the SLNs. Improved drug stability was further established by the appreciable shelf-life of the formulation from International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)-recommended accelerated stability studies. In vivo studies revealed nearly five-fold increase in the bioavailability of SR-1 (AUC0→∞=3411 ± 170.34 µg/ml/h) as compared to RV suspension (AUC0→∞=653.5 ± 30.10 µg/ml/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (serum glutamic oxalo-acetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase) after oral administration of RV-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections. Finally, reverse transcriptase-polymerase chain reaction studies were conducted on isolated liver mRNA from SR-1 treated animals and significant down-regulation of tissue inhibitor of metalloproteinases-1 and nuclear factor-kB was witnessed. PMID

  2. Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Yong Son

    2013-01-01

    Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

  3. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    Science.gov (United States)

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans. PMID:27058607

  4. LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol

    Science.gov (United States)

    Nøhr, Mark K.; Dudele, Anete; Poulsen, Morten M.; Ebbesen, Lene H.; Radko, Yulia; Christensen, Lars P.; Jessen, Niels; Richelsen, Bjørn; Lund, Sten; Pedersen, Steen B.

    2016-01-01

    Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS) resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin / delta0-15glucose) from 13.73 to 22.40 pmol/mmol (P < 0.001). This aberration in insulin and glucose homeostasis was normalized by resveratrol. In conclusion: Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin

  5. Substrates and enzyme activities related to biotransformation of resveratrol from phenylalanine by Alternaria sp. MG1.

    Science.gov (United States)

    Zhang, Jinhua; Shi, Junling; Liu, Yanlin

    2013-12-01

    To identify the substrates and enzymes related to resveratrol biosynthesis in Alternaria sp. MG1, different substrates were used to produce resveratrol, and their influence on resveratrol production was analyzed using high performance liquid chromatography (HPLC). Formation of resveratrol and related intermediates was identified using mass spectrum. During the biotransformation, activities of related enzymes, including phenylalanine ammonia-lyase (PAL), trans-cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL), were analyzed and tracked. The reaction system contained 100 mL 0.2 mol/L phosphate buffer (pH 6.5), 120 g/L Alternaria sp. MG1 cells, 0.1 g/L MgSO₄, and 0.2 g/L CaSO₄ and different substrates according to the experimental design. The biotransformation was carried out for 21 h at 28 °C and 120 rpm. Resveratrol formation was identified when phenylalanine, tyrosine, cinnamic acid, and p-coumaric acid were separately used as the only substrate. Accumulation of cinnamic acid, p-coumaric acid, and resveratrol and the activities of PAL, C4H, and 4CL were identified and changed in different trends during transformation with phenylalanine as the only substrate. The addition of carbohydrates and the increase of phenylalanine concentration promoted resveratrol production and yielded the highest value (4.57 μg/L) when 2 g/L glucose, 1 g/L cyclodextrin, and phenylalanine (4.7 mmol/L) were used simultaneously. PMID:24068334

  6. Co-spray dried resveratrol and budesonide inhalation formulation for reducing inflammation and oxidative stress in rat alveolar macrophages.

    Science.gov (United States)

    Trotta, Valentina; Lee, Wing-Hin; Loo, Ching-Yee; Young, Paul M; Traini, Daniela; Scalia, Santo

    2016-04-30

    Oxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroid responses in COPD patients. In this study, inhalable microparticles containing budesonide (BD) and resveratrol (RES) were prepared and characterized. This approach was undertaken to develop a multi-drug inhalable formulation with anti-oxidant and anti-inflammatory activities for treatment of chronic lung diseases. The inhalable microparticles containing different ratios of BD and RES were prepared by spray drying. The physico-chemical properties of the formulations were characterized in terms of surface morphology, particle size, physical and thermal stability. Additionally, in vitro aerosol performances of these formulations were evaluated with the multi-stage liquid impinger (MSLI) at 60 and 90l/min, respectively. The cytotoxicity effect of the formulations was evaluated using rat alveolar macrophages. The biological responses of alveolar macrophages in terms of cytokine expressions, nitric oxide (NO) production and free radical scavenging activities were also tested. The co-spray dried (Co-SD) microparticles of all formulations exhibited morphologies appropriate for inhalation administration. Analysis of the deposition profiles showed an increase in aerosol performance proportional to BD concentration. Cell viability assay demonstrated that alveolar macrophages could tolerate a wide range of RES and BD concentrations. In addition, RES and BD were able to decrease the levels of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced alveolar macrophages. This study has successfully established the manufacture of Co-SD formulations of RES and BD with morphology and aerosol properties suitable for inhalation drug delivery, negligible in vitro toxicity and enhanced

  7. Effects of Resveratrol on the Proliferation and Apoptosis in Synoviocytes of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    唐玲丽; 余平; 胡敏; 谢希; 陈新瑞

    2004-01-01

    This study was undertaken to investigate the regulatory effect of Resveratrol (Res) on the proliferation and apoptosis of synoviocytes of patients with rheumatoid arthritis (RA), as the proliferation of synoviocytes of patients was determined by MTT chromatometry and the apoptosis of these cells was assayed with TUNEL flow cytometry. It was found in this experiment that the degree of cell proliferation of the Res-treated group with dosages of 50-400 μM was significantly reduced in comparison with that of the control group, but percentage of the apoptotic cells demonstrated with TUNEL labeling was elevated under treatment with Res at the same dosages in a concentration-dependent manner. The difference between the Restreated group and the control group was quite significant ( P<0.01 ). It is concluded that Res shows a potent anti-proliferative effect on synoviocytes of patients with RA with induction of cell apoptosis, and it is likely a valuable candidate for the chemotherapy and management of patients with RA.

  8. Evaluation of Antioxidant Activity of Some Pteridophytes

    Directory of Open Access Journals (Sweden)

    Amit Semwal

    2013-04-01

    Full Text Available The present study was undertaken to find the antioxidant value of certain Pteridophytes in Garhwalregion. Antioxidants have been reported to prevent oxidative damage caused by free radical and can be used in cardiovascular and anti-inflammatory diseases to treat of burn and wounds. The methanolic crude extracts of some commonly used Pteridophytes were screened for their free radical scavengingproperties using ascorbic acid as standard antioxidant. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH free radical. The overall antioxidant activity of Diplaziumesculantum was the strongest, followed in descending order by Adiantumlunulatum, Pterisvittata, Equisetum romosissimumand Ampelopterisprolifera. All the methanolicextracts exhibited antioxidant activity significantly. The IC50 of the methanolic extracts ranged between 0.32 ± 0.12 and 0.81 ± 0.21 mg/ml. The study reveals that the consumption of these spices would exert several beneficial effects by virtue of their antioxidant activity.

  9. Antioxidants in skin ageing - Future of dermatology

    Directory of Open Access Journals (Sweden)

    Shamika M Salavkar

    2011-01-01

    Full Text Available The formation of free radicals is a widely accepted pivotal mechanism leading to skin ageing. Skin ageing is a complex, progressive, time-dependent deterioration caused by intrinsic and extrinsic factors or environmental factors. Skin is equipped with an elaborate antioxidant system that protects it from oxidative damage due to intrinsic and extrinsic factors. However, the natural antioxidant pool can be compromised or overwhelmed by oxidative stress of excess UV exposure, as well as cigarette smoke and other airborne pollutants. Topical antioxidants have been demonstrated to protect the skin from free radical damage and its regular application can actually reverse pervious photodamage. Topical antioxidants are available in over-the-counter skin care products that are aimed at preventing the clinical signs of photoageing. The present review summarises scientific literature regarding efficacy of topical antioxidants and significance of novel delivery systems for topical antioxidant delivery for combating skin ageing.

  10. Differential effects of resveratrol on androgen-responsive LNCaP human prostrate cancer cells in vitro and in vivo.

    Science.gov (United States)

    Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer chemopreventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and exami...

  11. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men

    NARCIS (Netherlands)

    Konings, E.; Timmers, S.; Boekschoten, M.V.; Goossens, G.H.; Jocken, J.W.; Afman, L.A.; Müller, M.R.; Schrauwen, P.; Mariman, E.C.; Blaak, E.E.

    2014-01-01

    Polyphenolic compounds, such as resveratrol, have recently received widespread interest because of their ability to mimic effects of calorie restriction. The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology a

  12. Resveratrol oligomers isolated from Carex species inhibit growth of human colon tumorigenic cells mediated by cell cycle arrest.

    Science.gov (United States)

    González-Sarrías, Antonio; Gromek, Samantha; Niesen, Daniel; Seeram, Navindra P; Henry, Geneive E

    2011-08-24

    Research has shown that members of the Carex genus produce biologically active stilbenoids including resveratrol oligomers. This is of great interest to the nutraceutical industry given that resveratrol, a constituent of grape and red wine, has attracted immense research attention due to its potential human health benefits. In the current study, five resveratrol oligomers (isolated from Carex folliculata and Carex gynandra ), along with resveratrol, were evaluated for antiproliferative effects against human colon cancer (HCT-116, HT-29, Caco-2) and normal human colon (CCD-18Co) cells. The resveratrol oligomers included one dimer, two trimers, and two tetramers: pallidol (1); α-viniferin (2) and trans-miyabenol C (3); and kobophenols A (4) and B (5), respectively. Although not cytotoxic, the resveratrol oligomers (1-5), as well as resveratrol, inhibited growth of the human colon cancer cells. Among the six stilbenoids, α-viniferin (2) was most active against the colon cancer cells with IC(50) values of 6-32 μM (>2-fold compared to normal colon cells). Moreover, α-viniferin (at 20 μM) did not induce apoptosis but arrested cell cycle (in the S-phase) for the colon cancer but not the normal colon cells. This study adds to the growing body of knowledge supporting the anticancer effects of resveratrol and its oligomers. Furthermore, Carex species should be investigated for their nutraceutical potential given that they produce biologically active stilbenoids such as α-viniferin. PMID:21761862

  13. Determination of polyphenol contents and antioxidant capacity of no-alcoholic red grape products (vitis labrusca from conventional and organic crops

    Directory of Open Access Journals (Sweden)

    Michel Mansur Machado

    2011-01-01

    Full Text Available The polyphenol contents and antioxidant capacity of Brazilian red grape juices and wine vinegars were analyzed. Additionally, it was analyzed the human polyphenol absorption and acute effect in plasmatic oxidative metabolism biomarkers after juice ingestion. The organic Bordo grape juice (GBO presented a higher level of trans-resveratrol, quercitin, rutin, gallic acid, caffeic acid and total flavonoids then other juices and vinegars as well as antioxidant capacity. The plasmatic polyphenol increased 27.2% after GBO juice ingestion. The results showed that juices and vinegars from Brazilian crops present similar chemical and functional properties described in studies performed in other countries.

  14. Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

    Science.gov (United States)

    Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

    2013-09-01

    Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

  15. Scavenging of Toxic Acrolein by Resveratrol and Hesperetin and Identification of Adducts.

    Science.gov (United States)

    Wang, Weixin; Qi, Yajing; Rocca, James R; Sarnoski, Paul J; Jia, Aiqun; Gu, Liwei

    2015-11-01

    The objective of this study was to investigate the ability of resveratrol and hesperetin to scavenge acrolein at pH 7.4 and 37 °C. About 6.4 or 5.2% of acrolein remained after reaction with resveratrol or hesperetin for 12 h at equimolar concentrations. An acrolein-resveratrol adduct and two acrolein-hesperetin adducts were isolated. Their structures were elucidated using mass and NMR spectroscopy. Acrolein reacted with resveratrol at the C-2 and C-3 positions through nucleophilic addition and formed an additional heterocyclic ring. Two similar monoacrolein-conjugated adducts were identified for hesperetin. Spectroscopic data suggested each acrolein-hesperetin adduct was a mixture of four stereoisomers due to the existence of two chiral carbon atoms. Yield of adducts was low at pH 5.4 but increased at pH 7.4 and 8.4. Higher pH also promoted the formation of diacrolein adducts. Results suggest that resveratrol and hesperetin exert health benefits in part through neutralizing toxic acrolein in vivo. PMID:26457480

  16. Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?

    Directory of Open Access Journals (Sweden)

    Juliana F. Saldanha

    2013-01-01

    Full Text Available Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promote transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2 activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD, are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

  17. Evolution of resveratrol and piceid contents during the industrial winemaking process of sherry wine.

    Science.gov (United States)

    Roldán, Ana; Palacios, Victor; Caro, Ildefonso; Pérez, Luis

    2010-04-14

    In the Jerez region, the sherry winemaking process involves a stage of aging carried out in a dynamic system known as "soleras" and "criaderas". In the case of fino sherry, this aging takes place in the presence of a yeast film growing on the surface of the wine, which gives it a very specific character. In this work, the influence of the sherry elaboration process on resveratrol and piceid levels has been studied. With this purpose, the contents of resveratrol isomers and piceid during the main stages of the sherry wine production system, from maturation until bottling, were monitored during two vintages. The results showed that resveratrol contents of both the skin and juice, for Palomino fino grape, are very similar to those described for other white grape varieties. Sherry wine fermentation, clarification, cold stabilization, and filtration processes considerably affect resveratrol and piceid contents. However, biological aging has the most important influence, diminishing their contents by 80%. These results were confirmed in several tests performed in the laboratory, in which various factors that could affect the resveratrol contents during aging were taken into account (oxidative phenomena and a combination with acetaldehyde and "flor" biofilm growth). PMID:20232794

  18. The effect of red wine extract, resveratrol, on the degree and rate of orthodontic tooth movement in guinea pigs

    Directory of Open Access Journals (Sweden)

    Isidro Alex C Urriquia

    2015-01-01

    Full Text Available Objective: An animal trial, its protocol approved by the Institutional Animal Care and Use Committee of the U.P. National Institutes of Health (IACUC Protocol No. 2010-008, was employed to investigate the effects of resveratrol on the degree and rate of orthodontic tooth movement in guinea pigs. Materials and Methods: Eighteen male adult guinea pigs were randomly allocated into 3 groups: low dose, high dose, and control groups. A 0.016" titanium molybdenum alloy wire formed into a helical torsion spring with a coil, with the loops cemented onto the maxillary incisors of the animals, served as the orthodontic appliance. Daily oral administration of resveratrol was provided to the low dose (0.047 mg/kg and high dose (0.47 mg/kg groups, while water was provided to the control group. Measurements were taken everyday at the interproximal area at the level of the incisal edge using a measuring caliper. Results: The results of the ANOVA showed no statistically significant differences in the mean measurements of tooth separation among the three groups from day 2 (P=0.966 to day 8 (P=0.056. However, starting from day 9 (P=0.049 until day 18 (P=0.000, there was a significant difference in the mean tooth separation among the test groups. Conclusion: Using the LSD, it was noted that the low dose and the high dose groups have similar degrees of mean tooth separation, with the control group being significantly different from the two.

  19. Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

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    Itsuo Murakami

    Full Text Available 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.

  20. Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice.

    Science.gov (United States)

    Dolinsky, Vernon W; Chakrabarti, Subhadeep; Pereira, Troy J; Oka, Tatsujiro; Levasseur, Jody; Beker, Donna; Zordoky, Beshay N; Morton, Jude S; Nagendran, Jeevan; Lopaschuk, Gary D; Davidge, Sandra T; Dyck, Jason R B

    2013-10-01

    Resveratrol (RESV) is a polyphenol with pleiotropic effects that include reduction of oxidative stress and increased vascular nitric oxide (NO) production. However, whether or not RESV can prevent rises in blood pressure (BP) is controversial and remains to be firmly established. The purpose of this study was to determine whether RESV attenuates elevated BP and subsequent adaptive cardiac hypertrophy and to better understand the mechanisms involved. The spontaneously hypertensive rat (SHR) and the angiotensin (Ang)-II infused mouse were used as hypertensive models. Compared to a standard control diet, consumption of diets containing RESV by SHRs and Ang-II hypertensive mice, markedly prevented rises in systolic BP. In addition, flow-mediated vasodilation was significantly improved by RESV in SHRs. RESV also reduced serum and cardiac levels of the lipid peroxidation by-product, 4-hydroxy-2-nonenal in the hypertensive rodents and inhibited the production of superoxide in human-derived endothelial cells. Analysis of mesenteric arteries from SHRs and Ang-II infused mice demonstrated that RESV increased endothelial NO synthase (eNOS) phosphorylation by enhancing the LKB1/adenosine monophosphate (AMP)-activated protein kinase (AMPK) signal transduction pathway. Moreover, RESV reduced hypertrophic growth of the myocardium through reduced hemodynamic load and inhibition of the p70 S6 kinase pro-hypertrophic signaling cascade. Overall, we show that high dose RESV reduces oxidative stress, improves vascular function, attenuates high BP and prevents cardiac hypertrophy through the preservation of the LKB1-AMPK-eNOS signaling axis. PMID:23707558

  1. Cardiac energy metabolism and oxidative stress biomarkers in diabetic rat treated with resveratrol.

    Directory of Open Access Journals (Sweden)

    Klinsmann Carolo dos Santos

    Full Text Available 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 (p<0.05 in these parameters. The glycemia decreased and higher final body weight increased in DM-RSV when compared with the DM group. The diabetic rats showed higher serum-free fatty acid, which was normalized with RSV. Oxygen consumption (VO2 and carbon dioxide production (VCO2 decreased (p<0.05 in the DM group. This was accompanied by reductions in RQ. The C-RSV group showed higher VO2 and VCO2 values. Pyruvate dehydrogenase activity was lower in the DM group and normalizes with RSV. The DM group exhibited higher myocardial β-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase activity, and RSV decreased the activity of these enzymes. The DM group had higher cardiac lactate 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

  2. Content of Phenolic Compounds and Antioxidant Capacity in Fruits of Apricot Genotypes

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    Helena Skutkova

    2010-09-01

    Full Text Available Research on natural compounds is increasingly focused on their effects on human health. In this study, we were interested in the evaluation of nutritional value expressed as content of total phenolic compounds and antioxidant capacity of new apricot (Prunus armeniaca L. genotypes resistant against Plum pox virus (PPV cultivated on Department of Fruit Growing of Mendel University in Brno. Fruits of twenty one apricot genotypes were collected at the onset of consumption ripeness. Antioxidant capacities of the genotypes were determined spectrometrically using DPPH• (1,1-diphenyl-2-picryl-hydrazyl free radicals scavenging test, TEAC (Trolox Equivalent Antioxidant Capacity, and FRAP (Ferric Reducing Antioxidant Powermethods. The highest antioxidant capacities were determined in the genotypes LE-3228 and LE-2527, the lowest ones in the LE-985 and LE-994 genotypes. Moreover, close correlation (r = 0.964 was determined between the TEAC and DPPH assays. Based on the antioxidant capacity and total polyphenols content, a clump analysis dendrogram of the monitored apricot genotypes was constructed. In addition, we optimized high performance liquid chromatography coupled with tandem electrochemical and spectrometric detection and determined phenolic profile consisting of the following fifteen phenolic compounds: gallic acid, 4-aminobenzoic acid, chlorogenic acid, ferulic acid, caffeic acid, procatechin, salicylic acid, p-coumaric acid, the flavonols quercetin and quercitrin, the flavonol glycoside rutin, resveratrol, vanillin, and the isomers epicatechin, (–- and (+- catechin.

  3. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome

    DEFF Research Database (Denmark)

    Morselli, Eugenia; Mariño, Guillermo; Bennetzen, Martin V; Eisenberg, Tobias; Megalou, Evgenia; Schroeder, Sabrina; Cabrera, Sandra; Bénit, Paule; Rustin, Pierre; Criollo, Alfredo; Kepp, Oliver; Galluzzi, Lorenzo; Shen, Shensi; Malik, Shoaib Ahmad; Maiuri, Maria Chiara; Horio, Yoshiyuki; López-Otín, Carlos; Andersen, Jens S.; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2011-01-01

    Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy...... independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation...... and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions...

  4. Antioxidant, Antitubercular and Cytotoxic Activities of Piper imperiale

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    Sanjib Bhakta

    2012-04-01

    Full Text Available Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to 6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin, ferulic acid, resveratrol and quercetin were identified and quantified by HPLC. DPPH and ABTS assays showed high antioxidant activity of the leaf extract (EC50ABTS = 15.6 µg/mL, EC50DPPH = 27.3 µg/mL with EC50 in the same order of magnitude as the hydroxyquinone (EC50ABTS = 10.2 µg/mL, EC50DPPH = 15.7 µg/mL. The flower extract showed strong antimicrobial activity against Mycobacterium tuberculosis H37Rv. All the extracts exhibited dose-dependent cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper extract has been found to be highly active against M. tuberculosis. This study shows the biological potential of Piper imperiale extracts and gives way to bio-guided studies with well-defined biological activities.

  5. Resveratrol and arsenic trioxide act synergistically to kill tumor cells in vitro and in vivo.

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    Xiao-Yan Zhao

    Full Text Available BACKGROUND AND AIMS: Arsenic trioxide (As2O3, which used as an effective agent in the treatment of leukaemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden heart death have been implicated in the cardiotoxicity of As2O3. The present study was designed to explore whether the combination of As2O3 and resveratrol could generate a more powerful anti-cancer effect both in vitro and in vivo. MATERIALS AND METHODS: MTT assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells. Isobolographic analysis was used to evaluate combination index values from cell viability data. The apoptosis and the cellular reactive oxygen species (ROS level were assessed by fluorescent microscopy and flow cytometry separately in vitro. The effect of As2O3, alone and in combination with resveratrol on Hela tumor growth in an orthotopic nude mouse model was also investigated. The tumor volume and the immunohistochemical analysis of CD31, CD34 and VEGF were determined. RESULTS: Resveratrol dramatically enhanced the anti-cancer effect induced by As2O3 in vitro. In addition, isobolographic analysis further demonstrated that As2O3 and resveratrol generated a synergistic action. More apoptosis and ROS generation were observed in the combination treatment group. Similar synergistic effects were found in nude mice in vivo. The combination of As2O3 and resveratrol dramatically suppressed both tumor growth and angiogenesis in nude mice. CONCLUSIONS: Combining As2O3 with resveratrol would be a novel strategy to treat cancer in clinical practice.

  6. Induction of resveratrol via UV irradiation effect in Ercis callus culture

    International Nuclear Information System (INIS)

    In this study, the effect of ultraviolet (UV) irradiation time, incubation time and callus age were investigated for resveratrol induction which is a stilbene compound, in callus cultures of ‘Ercis’ grape cultivar (Vitis vinifera L.). Callus tissues were obtained from the leaves of the cuttings grown in greenhouse. Gamborg B-5 media including 2% saccarose, 0.8% agar, 1.0 µM BAP (6-benzylaminopurine) and 0.1 µM 2, 4-D (2, 4- dichlorophenoxy-acetic acid) was used as culture media. Callus tissues were sub cultured two times with 21 days intervals. After the second subculture, 12 and 15 days old callus tissues were exposed to 254 nm UV light at 10 cm distance from the source for 10 and 15 min by opening covers of the petri dishes in sterile cabin. After UV treatment, callus tissues were incubated at 25°C and in dark conditions. High Pressure Liquid Chromatography (HPLC) was used for determining of resveratrol production and concentrations were recorded at 0, 24, 48 and 72 hours after beginning of incubation. The highest resveratrol concentration (66.39 µg/g FW) was determined at 48 hours of 12 days-old callus cultures irradiated for 10 minutes. Generally, resveratrol accumulation in 12 days-old callus cultures was higher than that of 15 days-old. Both 10 min and 15 min UV irradiation periods were found to be effective for induction of resveratrol production and thus callus cultures could be convenient for resveratrol production. (author)

  7. Encapsulation of mixtures of tuna oil, tributyrin and resveratrol in a spray dried powder formulation.

    Science.gov (United States)

    Sanguansri, Luz; Day, Li; Shen, Zhiping; Fagan, Peter; Weerakkody, Rangika; Cheng, Li Jiang; Rusli, Jenny; Augustin, Mary Ann

    2013-12-01

    Spray dried emulsions are effective for carrying and stabilising combinations of fish oil and tributyrin, fish oil and resveratrol, or fish oil, tributyrin and resveratrol in one formulation. The encapsulation efficiencies were >99% for all three bioactives when a heated mixture of sodium caseinate: glucose: dried glucose syrup matrix (Encapsulant matrix 1) was used. When a heated sodium caseinate: glucose: processed starch matrix (Encapsulant matrix 2) was used, the encapsulation efficiencies were 90-92% for tributyrin and approximately 98% for resveratrol for all formulations but 79-91% for tuna oil where the efficiency was more formulation dependent. There was 84-86% remaining EPA, 85-87% remaining DHA, 85% remaining tributyrin and 94-96% remaining resveratrol after 18 months at 25 °C storage of the spray dried emulsions using Encapsulant matrix 1 across all formulations. In comparison, there was 83-87% remaining EPA and 84-89% remaining DHA, 80-82% remaining tributyrin, and 81-100% remaining resveratrol across all formulations with Encapsulant matrix 2. In vitro studies showed that on sequential exposure to simulated gastric and intestinal fluids, <5% tuna oil was found as triglycerides, but all the tributyrin had been lipolysed. The presence of diglycerides, monoglycerides and free fatty acids in the in vitro digests suggested that lipolysis of tuna oil had occurred. The type of matrix used for encapsulating the bioactives had little effect on the lipolysis of the oils but affected the amount of solvent extractable resveratrol. The ability of delivering mixtures of bioactives within one formulation was demonstrated. PMID:24121865

  8. Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro.

    Science.gov (United States)

    Shakibaei, Mehdi; Mobasheri, Ali; Buhrmann, Constanze

    2011-05-01

    The mitogen-activated protein kinase (MAPK) pathway is stimulated in differentiated chondrocytes and is an important signaling cascade for chondrocyte differentiation and survival. Pro-inflammatory cytokines such as interleukin 1β (IL-1β) play important roles in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this study, we investigated whether curcumin and resveratrol can synergistically inhibit the catabolic effects of IL-1β, specifically the inhibition of the MAPK and subsequent apoptosis in human articular chondrocytes. Chondrocytes were either left untreated or treated with 10 ng/ml IL-1β or 1 μM U0126, a specific inhibitor of MAPK pathway alone for the indicated time periods or pre-treated with 10 μM curcumin, 10 μM resveratrol or 10 μM resveratrol and 10 μM curcumin for 4 h followed by co-treatment with 10 ng/ml IL-1β or 1 μM U0126 and 10 μM resveratrol, 10 μM curcumin or 10 μM resveratrol and 10 μM curcumin for the indicated time periods. Cultures were evaluated by immunoblotting and transmission electron microscopy. Incubation of chondrocytes with IL-1β resulted in induction of apoptosis, downregulation of β1-integrins and the extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, U0126 induced apoptosis and blocked the above-mentioned proteins in a similar way to IL-1β. Furthermore, curcumin and resveratrol inhibited IL-1β- or U0126-induced apoptosis and downregulation of β1-integrins and Erk1/2 in human articular chondrocytes. These results suggest that combining these two natural compounds activates MEK/Erk signaling, a pathway that is involved in the maintenance of chondrocyte differentiation and survival. PMID:21484156

  9. Antioxidant-Induced Stress

    Directory of Open Access Journals (Sweden)

    Robert D. Kross

    2012-02-01

    Full Text Available Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals.

  10. Resveratrol Represses Pokemon Expression in Human Glioma Cells.

    Science.gov (United States)

    Yang, Yutao; Cui, Jiajun; Xue, Feng; Overstreet, Anne-Marie; Zhan, Yiping; Shan, Dapeng; Li, Hui; Li, Hui; Wang, Yongjun; Zhang, Mengmeng; Yu, Chunjiang; Xu, Zhi-Qing David

    2016-03-01

    POK erythroid myeloid ontogenic factor (Pokemon), an important proto-oncoprotein, is a transcriptional repressor that regulates the expression of many genes and plays an important role in tumorigenesis. Resveratrol (RSV), a natural polyphenolic compound, has many beneficial biological effects on health. In this study, we investigated the role of Pokemon in RSV-induced biological effects and the effect of RSV on the expression of Pokemon in glioma cells. We found that overexpression of Pokemon decreased RSV-induced cell apoptosis, senescence, and anti-proliferative effects. Moreover, we showed that RSV could efficiently decrease the activity of the Pokemon promoter and the expression of Pokemon. Meanwhile, RSV also inhibited Sp1 DNA binding activity to the Pokemon promoter; whereas, it did not influence the expression and nuclear translocation of Sp1. In addition, we found that RSV could increase the recruitment of HDAC1, but decreased p300 to the Pokemon promoter. Taken together, all these results extended our understanding on the anti-cancer mechanism of RSV in glioma cells. PMID:25875864

  11. Evaluating the Effect of Expressing a Peanut Resveratrol Synthase Gene in Rice

    OpenAIRE

    Zheng, Shigang; Zhao, Shanchang; Li, Zhen; Wang, Qingguo; Yao, Fangyin; Yang, Lianqun; Pan, Jiaowen; Liu, Wei

    2015-01-01

    Resveratrol (Res) is a type of natural plant stilbenes and phytoalexins that only exists in a few plant species. Studies have shown that the Res could be biosynthesized and accumulated within plants, once the complete metabolic pathway and related enzymes, such as the key enzyme resveratrol synthase (RS), existed. In this study, a RS gene named PNRS1 was cloned from the peanut, and the activity was confirmed in E. coli. Using transgenic approach, the PNRS1 transgenic rice was obtained. In T3 ...

  12. Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

    OpenAIRE

    Tomé-Carneiro, Joao; Larrosa, Mar; González-Sarrías, Antonio; Tomás-Barberán, Francisco A.; García-Conesa, María Teresa; Espín, Juan Carlos

    2013-01-01

    Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of food-stuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In li...

  13. Analysis and Quantification of trans-Resveratrol in Wines from Alentejo Region (Portugal)

    OpenAIRE

    Ratola, Nuno; Luís Faria, Joaquim; Alves, Arminda

    2004-01-01

    A simple procedure for determination of trans-resveratrol in wines from Alentejo region delimited appellation (Portugal) is described and validated. A set of 47 red and 21 white wines was analysed by direct injection in high performance liquid chromatograph with UV detector. A detection limit of 0.06 mg/L was achieved. Global uncertainty associated with the results, according to EURACHEM/CITAC rules, ranged from 16.33 to 27.15 %. Trans-resveratrol was detected in all red wines and in 8 white ...

  14. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients

    OpenAIRE

    Movahed, Ali; Nabipour, Iraj; Lieben Louis, Xavier; Thandapilly, Sijo Joseph; Yu, Liping; Kalantarhormozi, Mohammadreza; Rekabpour, Seyed Javad; Netticadan, Thomas

    2013-01-01

    The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of standard antidiabetic treatment in patients with type 2 diabetes, in a randomized placebo-controlled double-blinded parallel clinical trial. A total of 66 subjects with type 2 diabetes were enrolled in this study and randomly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets....

  15. Cancer-specific Therapeutic Potential of Resveratrol: Metabolic Approach against Hallmarks of Cancer

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    Dong Hoon Suh

    2013-08-01

    Full Text Available ABSTRACTCancer hallmarks include evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. Cancer cells undergo metabolic reprogramming and inevitably take advantage of glycolysis to meet the increased metabolic demand: rapid energy generation and macromolecular synthesis. Resveratrol, a polyphenolic phytoalexin, is known to exhibit pleiotropic anti-cancer effects most of which are linked to metabolic reprogramming in cancer cells. This review summarizes various anti-cancer effects of resveratrol in the context of cancer hallmarks in relation to metabolic reprogramming.

  16. Anti-oxidant properties and polyphenolic profile screening of Vitis vinifera stems and leaves crude extracts grown in Perlis, Malaysia

    Science.gov (United States)

    Zakaria, Nursyahda; Zulkifli, Razauden Mohamed; Akhir, Fazrena Nadia Md; Basar, Norazah

    2014-03-01

    Grape has become a fast growing agricultural sector in Malaysia producing between 0.62 kg to 2.03 kg waste per vinestock. This study aims to generate useful information on anti-oxidative properties as well as polyphenolic composition of grapevine waste. Stems and leaves of Vitis vinifera cultivated in Perlis, Malaysia were extracted using methanol, ethyl acetate and petroleum ether. Ethyl acetate stems extract exhibited highest total phenolic content. While in DPPH assay, methanolic stems extract show the highest antioxidant activities. This result indicates that total phenolic content in the extracts may not contribute directly to the antioxidant activities. Thin Layer Chromatograms of all crude extracts exhibited good separation under solvent system petroleum ether-ethyl acetate (2:3) resulted in detection of resveratrol in ethyl acetate stems crude extract.

  17. Antioxidant compounds and antioxidant activity in "early potatoes".

    Science.gov (United States)

    Leo, Lucia; Leone, Antonella; Longo, Cristiano; Lombardi, Domenico Antonio; Raimo, Francesco; Zacheo, Giuseppe

    2008-06-11

    The antioxidant content and the antioxidant capacity of both hydrophilic and lipophilic antioxidant extracts from four "early potato" cultivars, grown in two different locations (Racale and Monteroni), were examined. There was a considerable variation in carotenoid content and weak differences in the ascorbic acid concentration of the examined cultivars of "early potato" and between the harvested locations. An increase in both methanol/water (8:2 v/v) and phosphate buffer soluble (PBS) free phenols (70%) and bound phenols (28%) in the extracts from the cultivars grown at Racale site was found and discussed. Examination of individual phenols revealed that chlorogenic acid and catechin were the major phenols present in potato tuber extracts; a moderate amount of caffeic acid and ferulic acid was also detected. The total equivalent antioxidant capacity (TEAC) was higher in the Racale extracts and a highly positive linear relationship ( R (2) = 0.8193) between TEAC values and total phenolic content was observed. The oxyradical scavenging capacity (TOSC) of methanol/water and PBS extracts of peel and whole potatoes against the reactive oxygen species (ROS) peroxyl radicals, peroxynitrite, and hydroxyl radicals was also analyzed. A highly significant linear correlation ( R (2) = 0.9613) between total antioxidant capacity (as a sum of peroxyl radicals + peroxynitrite) and total phenol content of methanol/water extracts was established. Moreover, proliferation of human mammalian cancer (MCF-7) cells was significantly inhibited in a dose-dependent manner after exposure to potato extracts. These data can be useful for "early potato" tuber characterization and suggest that the "early potato" has a potential as a dietary source of antioxidants. PMID:18476702

  18. ANTIOXIDANT STATUS IN DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Giriraja

    2015-12-01

    Full Text Available BACKGROUND Hyperglycemia and dislipidemia in DM induce increased lipid peroxdation and free radical formation. This is an important mechanism of microangiopathy. AIM To measure the antioxidant status in type 2 DM with nephropathy and compared with nondiabetic control group. MATERIALS AND METHODS 50 type 2 DM patients aged between 50 to 70 years according to national diabetes data group criteria with nephropathy diagnosed on the basis of history, physical examination and biochemical parameters were included. 50 age and sex matched apparently healthy individuals with normal plasma glucose, normal renal parameters and with no symptoms suggestive of DM were taken as controls. RESULTS Antioxidant status was significantly less in patients with diabetic nephropathy. CONCLUSION Data suggests that alteration in antioxidant status may help predict the risk of diabetic nephropathy.

  19. Resveratrol Decreases TXNIP mRNA and Protein Nuclear Expressions With an Arterial Function Improvement in Old Mice.

    Science.gov (United States)

    Bedarida, Tatiana; Baron, Stephanie; Vibert, Françoise; Ayer, Audrey; Henrion, Daniel; Thioulouse, Elizabeth; Marchiol, Carmen; Beaudeux, Jean-Louis; Cottart, Charles-Henry; Nivet-Antoine, Valerie

    2016-06-01

    Aging leads to a high prevalence of glucose intolerance and cardiovascular diseases, with oxidative stress playing a potential role. Resveratrol has shown promising effects on glucose tolerance and tends to improve endothelial function in elderly patients. Thioredoxin-interacting protein (TXNIP) was recently proposed as a potential link connecting glucose metabolism to oxidative stress. Here, we investigated the resveratrol-induced improvement of arterial aging phenotype in old mice and the expression of aortic TXNIP. Using an in vivo model of old mice with or without 3-month resveratrol treatment, we investigated the effects of resveratrol on age-related impairments from a cardiovascular Doppler analysis, to a molecular level, by studying inflammation and oxidative stress factors. We found a dual effect of resveratrol, with a decrease of age-related glucose intolerance and oxidative stress imbalance leading to reduced matrix remodeling that forestalls arterial aging phenotype in terms of intima-media thickness and arterial distensibility. These results provide the first evidence that aortic TXNIP mRNA and protein nuclear expressions are increased in the arterial aging and decreased by resveratrol treatment. In conclusion, we demonstrated that resveratrol helped to restore several aging impaired processes in old mice, with a decrease of aortic TXNIP mRNA and protein nuclear expressions. PMID:26041427

  20. Antioxidant-Induced Stress

    OpenAIRE

    Robert D. Kross; Cleva Villanueva

    2012-01-01

    Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that...

  1. Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum.

    Science.gov (United States)

    De Santi, C; Pietrabissa, A; Spisni, R; Mosca, F; Pacifici, G M

    2000-06-01

    1. Resveratrol, a polyphenolic compound present in grapes and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. It is present in the diet, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim was to study the sulphation of resveratrol in the human liver and duodenum. 2. A simple and reproducible radiometric assay for resveratrol sulphation was developed. It employed 3'-phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/- 21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM) was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39) and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n = 5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum), those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum), and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a flavonoid present in wine, fruits and vegetables, suggests that compounds present in the diet may inhibit the sulphation of resveratrol, thus improving its bioavailability. PMID:10923862

  2. Antioxidants in dermatology

    OpenAIRE

    Pai, Varadraj V; Pankaj Shukla; Naveen Narayanshetty Kikkeri

    2014-01-01

    Antioxidants neutralize free radicals produced by various environmental insults such as ultraviolet radiation, cigarette smoke and air pollutants, thereby preventing cellular damage. The role of oxidative stress and antioxidants is known in diseases like obesity, atherosclerosis, and Alzheimer's disease. Herein we discuss the effects of oxidative stress on the skin and role of antioxidants in dermatology.

  3. Antioxidants in dermatology

    Directory of Open Access Journals (Sweden)

    Varadraj V Pai

    2014-01-01

    Full Text Available Antioxidants neutralize free radicals produced by various environmental insults such as ultraviolet radiation, cigarette smoke and air pollutants, thereby preventing cellular damage. The role of oxidative stress and antioxidants is known in diseases like obesity, atherosclerosis, and Alzheimer′s disease. Herein we discuss the effects of oxidative stress on the skin and role of antioxidants in dermatology.

  4. Transient Transfection of a Wild-Type p53 Gene Triggers Resveratrol-Induced Apoptosis in Cancer Cells

    OpenAIRE

    Ferraz da Costa, Danielly Cristiny; Casanova, Fabiana Alves; Quarti, Julia; Malheiros, Maitê Santos; Sanches, Daniel; dos Santos, Patricia Souza; Fialho, Eliane; Silva, Jerson L.

    2012-01-01

    Resveratrol is a promising chemopreventive agent that mediates many cellular targets involved in cancer signaling pathways. p53 has been suggested to play a role in the anticancer properties of resveratrol. We investigated resveratrol-induced cytotoxicity in H1299 cells, which are non-small lung cancer cells that have a partial deletion of the gene that encodes the p53 protein. The results for H1299 cells were compared with those for three cell lines that constitutively express wild-type p53:...

  5. Experimental Studies of the Molecular Pathways Regulated by Exercise and Resveratrol in Heart, Skeletal Muscle and the Vasculature

    Directory of Open Access Journals (Sweden)

    Vernon W. Dolinsky

    2014-09-01

    Full Text Available Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of exercise training and resveratrol on some of the organs and tissues that act in concert to transport oxygen throughout the body. In particular, we focus on animal studies that investigate the molecular signaling pathways induced by these interventions. We also compare and contrast the effects of exercise and resveratrol in diseased states.

  6. Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-κB pathway in human epidermoid carcinoma A431 cells

    International Nuclear Information System (INIS)

    Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm2) and resveratrol (60 μM) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-κB) pathway by blocking phosphorylation of serine 536 and inactivating NF-κB and subsequent degradation of IκBα, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.

  7. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  8. Pharmacokinetics, biodistribution, in vitro cytotoxicity and biocompatibility of Vitamin E TPGS coated trans resveratrol liposomes.

    Science.gov (United States)

    Vijayakumar, Mahalingam Rajamanickam; Vajanthri, Kiran Yellappa; Balavigneswaran, Chelladurai Karthikeyan; Mahto, Sanjeev Kumar; Mishra, Nira; Muthu, Madaswamy S; Singh, Sanjay

    2016-09-01

    The clinical application of trans resveratrol (RSV) in glioma treatment is largely limited because of its rapid metabolism, fast elimination from systemic circulation and low biological half life. Therefore, the objectives of this study were to enhance the circulation time, biological half life and passive brain targeting of RSV using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) coated liposomes (RSV-TPGS-Lipo). In addition to basic liposomal characterizations, in vitro anticancer potential against C6 glioma cell lines and cellular internalization of liposomes were carried out by MTT assay and confocal laser scanning microscopy (CLSM), respectively. Pharmacokinetics and tissue distribution studies were also carried out after intravenous administration in Charles Foster rats. RSV-TPGS-Lipo 2 showed significantly higher cytotoxicity than RSV-Lipo (uncoated liposomes) and RSV. Both uncoated and TPGS coated liposomes showed excellent cellular uptake. RSV, RSV-Lipo and RSV-TPGS-Lipo 2 were found to be haemocompatible and safe after i.v. administration. Area under the curve (AUC) and plasma half life (t1/2) after i.v. administration of RSV-TPGS-Lipo 2 was found to be approximately 5.73 and 6.72 times higher than that of RSV-Lipo as well as 29.94 and 29.66 times higher than that of RSV, respectively. Thus, the outcome indicates that RSV-TPGS-Lipo 2 is a promising carrier for glioma treatment with improved pharmacokinetic parameters. Moreover, brain accumulation of RSV-Lipo and RSV-TPGS-Lipo 2 was found to be significantly higher than that of RSV (P<0.05). Results are suggesting that both RSV-Lipo and RSV-TPGS-Lipo 2 are the promising tools of RSV for the treatment of brain cancer. PMID:27236510

  9. Beneficial effects of combined resveratrol and metformin therapy in treating diet-induced insulin resistance.

    Science.gov (United States)

    Frendo-Cumbo, Scott; MacPherson, Rebecca E K; Wright, David C

    2016-08-01

    The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low- (LFD; 10% Kcal from fat) or high-fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue-specific insulin signaling were measured 4 weeks post-treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin-stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis. PMID:27482073

  10. Repressive effects of resveratrol on androgen receptor transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Wen-feng Shi

    Full Text Available BACKGROUND: The chemopreventive effects of resveratrol (RSV on prostate cancer have been well established; the androgen receptor (AR plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity. METHODOLOGY: The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of AR-negative HeLa cells to generate the AR(+ cells. The constitutively expressed AR was characterized by monitoring hormone-stimulated nuclear translocation, DNA binding, and transcriptional activation, with the AR(- cells serving as controls. AR(+ cells were treated with RSV, and both AR protein levels and AR transcriptional activity were measured simultaneously. Chromatin immunoprecipitation (ChIP assays were used to detect the effects of RSV on the recruitment of AR to its cognate element (ARE. RESULTS: AR in the AR (+ stable cell line functions in a manner similar to that of endogenously expressed AR. Using this model system we clearly demonstrated that RSV represses AR transcriptional activity independently of any effects on AR protein levels. However, neither the hormone-mediated nucleus translocation nor the AR/ARE interaction was affected by RSV treatment. CONCLUSION: We demonstrated unambiguously that RSV regulates AR target gene expression, at least in part, by repressing AR transcriptional activity. Repressive effects of RSV on AR activity result from mechanisms other than the affects of AR nuclear translocation or DNA binding.

  11. Pharmacological and dietary antioxidant therapies for chronic obstructive pulmonary disease.

    Science.gov (United States)

    Biswas, S; Hwang, J W; Kirkham, P A; Rahman, I

    2013-01-01

    The progression and exacerbations of chronic obstructive pulmonary disease (COPD) are intimately associated with tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress. Alterations in redox signaling proinflammatory kinases and transcription factors, steroid resistance, unfolded protein response, mucus hypersecretion, extracellular matrix remodeling, autophagy/apoptosis, epigenetic changes, cellular senescence/aging, endothelial dysfunction, autoimmunity, and skeletal muscle dysfunction are some of the pathological hallmarks of COPD. In light of the above it would be prudent to target systemic and local oxidative stress with agents that can modulate the antioxidants/ redox system or by boosting the endogenous levels of antioxidants for the treatment and management of COPD. Identification of various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine lysine salt), dietary natural product-derived polyphenols and other compounds (curcumin, resveratrol, green tea catechins, quercetin sulforaphane, lycopene, acai, alpha-lipoic acid, tocotrienols, and apocynin) have made it possible to modulate various biochemical aspects of COPD. Various researches and clinical trials have revealed that these antioxidants can detoxify free radicals and oxidants, control expression of redox and glutathione biosynthesis genes, chromatin remodeling, and ultimately inflammatory gene expression. In addition, modulation of cigarette smoke-induced oxidative stress and related cellular changes have also been reported to be effected by synthetic molecules. This includes specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, lipid peroxidation and protein carbonylation blockers/inhibitors, such as edaravone and lazaroids

  12. Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation

    DEFF Research Database (Denmark)

    Boissy, Patrice; Andersen, Thomas L; Abdallah, Basem M;

    2005-01-01

    challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. Because resveratrol (trans-3,4',5-trihydroxystilbene) is reported to display antitumor activities on a variety of human cancer cells, we investigated the effects of this...... attention as potential drugs for treating multiple myeloma....

  13. Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men

    DEFF Research Database (Denmark)

    Olesen, Jesper; Gliemann Hybholt, Lasse; Biensøe, Rasmus S;

    2014-01-01

    , resveratrol blunted an exercise training-induced decrease (~20%) in protein carbonylation and decrease (~40%) in TNFα mRNA content in skeletal muscle. Conclusion: Resveratrol did not elicit metabolic improvements in healthy aged subjects; in fact resveratrol even impaired the observed exercise training......Aim: To investigate the metabolic and anti-inflammatory effects of resveratrol alone and when combined with exercise training in skeletal muscle of aged human subjects. Material and Methods: Healthy physically inactive men (60-72 year old) were randomized into either 8 weeks of daily intake of 250...... training increased skeletal muscle PGC-1α mRNA ~1.5-fold, cytochrome c protein ~1.3 fold, cytochrome c oxidase I protein ~1.5-fold, citrate synthase activity ~1.3-fold, 3-hydroxyacyl-CoA dehydrogenase activity ~1.3-fold, IκB-α and IκB-β protein content ~1.3-fold and time to exhaustion in KEE by ~1.2-fold...

  14. Anti-inflammatory effect of resveratrol on TNF-α-induced MCP-1 expression in adipocytes

    International Nuclear Information System (INIS)

    Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-α-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-α-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-α-induced MCP-1 transcription. Nuclear factor (NF)-κB was determined to play a major role in the TNF-α-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-κB complex and subsequently suppressed NF-κB transcriptional activity in TNF-α-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies

  15. Cancer-specific Therapeutic Potential of Resveratrol: Metabolic Approach against Hallmarks of Cancer

    OpenAIRE

    Dong Hoon Suh; Mi-Kyung Kim; Hee Seung Kim; Hyun Hoon Chung; Yong Sang Song

    2013-01-01

    ABSTRACTCancer hallmarks include evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. Cancer cells undergo metabolic reprogramming and inevitably take advantage of glycolysis to meet the increased metabolic demand: rapid energy generation and macromolecular synthesis. Resveratrol, a polyphenolic phytoalexin, is known to exhibit pleiotropic anti-cancer effects most of which are linked to metabolic reprogramming in cancer cells. This review...

  16. Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice

    DEFF Research Database (Denmark)

    Ringholm, Stine; Olesen, Jesper; Pedersen, Jesper Thorhauge;

    2013-01-01

    The present study tested the hypothesis that lifelong resveratrol (RSV) supplementation counteracts an age-associated decrease in skeletal muscle oxidative capacity through peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and that RSV combined with lifelong exercise training (ET...

  17. Isolation of Resveratrol from Vitis Viniferae Caulis and Its Potent Inhibition of Human Tyrosinase

    Directory of Open Access Journals (Sweden)

    Jiaa Park

    2013-01-01

    Full Text Available Tyrosinase (TYR catalyzes rate-limiting reactions of cellular melanin synthesis, and its inhibitors are of commercial interest as potential skin whitening agents. However, the limited availability of human TYR makes the screening of TYR inhibitors difficult. To overcome this hurdle, we transformed nonmelanocytic human embryonic kidney (HEK 293 cells to express human TYR constitutively. Using these cells as a source of human TYR, the ethanolic extracts of 52 medicinal plants grown in Korea were tested for human TYR activity, and the extract of Vitis Viniferae Caulis (dried stems of the grape tree, Vitis vinifera L. was found to inhibit human TYR activity potently. An active compound was isolated from this extract by solvent fractionation followed by liquid column chromatography and identified as resveratrol by spectroscopic and chromatographic analyses. Resveratrol was determined to be a highly potent inhibitor of human TYR (IC50=0.39 μg mL−1 as compared with p-coumaric acid (IC50=0.66 μg mL−1 and arbutin (IC50>100 μg mL−1 and inhibited melanin synthesis by human epidermal melanocytes at subtoxic concentrations. This study suggests that resveratrol and resveratrol-containing extracts of Vitis Viniferae Caulis have a potential use as skin whitening agents.

  18. On the Molecular Pharmacology of Resveratrol on Oxidative Burst Inhibition in Professional Phagocytes

    Czech Academy of Sciences Publication Activity Database

    Nosáľ, R.; Drábiková, K.; Jančinová, V.; Perečko, T.; Ambrožová, Gabriela; Číž, Milan; Lojek, Antonín; Pekarová, Michaela; Šmidrkal, J.; Harmatha, Juraj

    2014-01-01

    Roč. 2014, Jan 28 (2014), 706269/1-706269/9. ISSN 1942-0900 Institutional support: RVO:61388963 ; RVO:68081707 Keywords : resveratrol * oxidative burst * human neutrophils Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.516, year: 2014 http://www.hindawi.com/journals/omcl/2014/706269/

  19. Physical Methods of Resveratrol Induction in Grapes and Grape Products – A Review

    Czech Academy of Sciences Publication Activity Database

    Tříska, Jan; Houška, M.

    2012-01-01

    Roč. 30, č. 6 (2012), s. 489-502. ISSN 1212-1800 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MZe QI91B094 Institutional support: RVO:67179843 Keywords : trans-resveratrol * methods of enchrichements * UV irradiation * ozonisation Subject RIV: EH - Ecology, Behaviour Impact factor: 0.685, year: 2012

  20. The influence of the grapevine treatment on the content of resveratrol and other phenolic compounds

    Czech Academy of Sciences Publication Activity Database

    Kyseláková, M.; Balík, J.; Veverka, J.; Tříska, Jan; Vrchotová, Naděžda; Totušek, J.; Lefnerová, D.

    Vienna: Markus Pirchner GesmbH, 2004, s. -. [OIV - Congress 2004.. Vienna (AT), 04.07.2004-09.07.2004] R&D Projects: GA MZe QD1155 Institutional research plan: CEZ:AV0Z6087904 Keywords : resveratrol * grapevine treatment * phenolic compounds Subject RIV: CB - Analytical Chemistry, Separation

  1. Resveratrol v červených vínech

    Czech Academy of Sciences Publication Activity Database

    Kyseláková, M.; Balík, J.; Veverka, J.; Tříska, Jan; Vrchotová, Naděžda; Totušek, J.; Lefnerová, D.

    2003-01-01

    Roč. 96, 7-8 (2003), s. 357-358. ISSN 1212-7884 R&D Projects: GA MZe QD1155 Institutional research plan: CEZ:AV0Z6087904 Keywords : resveratrol * red wine Subject RIV: CB - Analytical Chemistry, Separation

  2. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases

    NARCIS (Netherlands)

    Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L.; Kim, Myung K.; Beaven, Michael A.; Burgin, Alex B.; Manganiello, Vincent; Chung, Jay H.

    2012-01-01

    Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resverat

  3. The protective effect of antioxidants on liquid and frozen stored ram semen

    Directory of Open Access Journals (Sweden)

    Csilla Budai

    2014-05-01

    Full Text Available This systematic review is focusing on the current literature in order to give an overview of the protective role of antioxidants in ram semen preservation. Throughout the sperm conservation process the unsaturated fatty acids of the spermatozoa membrane binds oxygen and evolves numerous peroxide bonds. The lipid peroxidation leads to unbalanced oxidative stress that causes different impairments of sperm cells, and acrosome loss. ,,Cold shock” also induces caspase cascade involved in apoptosis, DNA fragmentation and in overall it has a detrimental effect on the fertilizing capacity of spermatozoa. Nowadays the cryop