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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. Antioxidant effects of resveratrol in the cardiovascular system.

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    Xia, Ning; Daiber, Andreas; Förstermann, Ulrich; Li, Huige

    2017-06-01

    The antioxidant effects of resveratrol (3,5,4'-trihydroxy-trans-stilbene) contribute substantially to the health benefits of this compound. Resveratrol has been shown to be a scavenger of a number of free radicals. However, the direct scavenging activities of resveratrol are relatively poor. The antioxidant properties of resveratrol in vivo are more likely to be attributable to its effect as a gene regulator. Resveratrol inhibits NADPH oxidase-mediated production of ROS by down-regulating the expression and activity of the oxidase. This polyphenolic compound reduces mitochondrial superoxide generation by stimulating mitochondria biogenesis. Resveratrol prevents superoxide production from uncoupled endothelial nitric oxide synthase by up-regulating the tetrahydrobiopterin-synthesizing enzyme GTP cyclohydrolase I. In addition, resveratrol increases the expression of various antioxidant enzymes. Some of the gene-regulating effects of resveratrol are mediated by the histone/protein deacetylase sirtuin 1 or by the nuclear factor-E2-related factor-2. In this review article, we have also summarized the cardiovascular effects of resveratrol observed in clinical trials. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. © 2016 The British Pharmacological Society.

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

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    Zhigang Zhang

    2014-01-01

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

  4. Anti-oxidative effect of resveratrol on aluminum induced toxicity in rat cerebral tissue.

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    Zakaria, M M H; Hajipour, B; Estakhri, R; Saleh, B M

    2017-01-01

    The direct protective effects of resveratrol against oxidative stress have been demonstrated in neuroglial cells, the mechanisms of these effects are not fully understood. The aim of this research was to study the effect of resveratrol on AL induced cerebral injury in rat. We divided the groups as follows with 10 animals each: a) Group I - served as control receiving normal drinking water and diet ad libitum. b) Group II - animals were administered aluminum at a dose level of 100 mg/kg body weight for a period of 6 weeks daily through oral gavage. c) Group III - animals were administered aluminum at a dose level of 100 mg/kg body weight and resveratrol at a dose of 10 mg/kg body weight intraperitoneally for a period of 6 weeks daily. After 6 weeks rats were anesthetized and decapitated. Brains were removed immediately and frozen in liquid nitrogenRESULTS: The levels of SOD and GPx antioxidant enzymes were decreased in all of the groups receiving aluminium, but it was less severe in resveratrol treated group. SOD and GPx levels in aluminium + resveratrol group were higher than in the aluminum group (p aluminum group and the difference was significant (p toxicity by reducing MDA production in cerebral tissue. Resveratrol also attenuated SOD and GPx suppression in cerebral tissue significantly. Our findings provide the rationale for further studies directed to understanding the mechanism of resveratrol in preventing neurodeterioration (Tab. 1, Ref. 35).

  5. Comparative biochemical responses and antioxidant activities of the rabbit urinary bladder to whole grapes versus resveratrol.

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    Francis, Johdi-Ann; Leggett, Robert E; Schuler, Catherine; Levin, Robert M

    2015-12-01

    The objective of this study is to compare the antioxidant activity of a whole-grape suspension with the antioxidant activity or pure resveratrol on the effect of hydrogen peroxide (H2O2) on malondialdehyde (MDA) generation, choline acetyltransferase (ChAT) activity, calcium ATPase activity, and sarcoendoplasmic reticular ATPase (SERCA) of the male rabbit urinary bladder. MDA was used as a model for the effect of H2O2 on lipid peroxidation. ChAT, SERCA, and calcium ATPase were evaluated based on their importance in urinary bladder physiology and pathology. Four male rabbit bladders were used. Each bladder was separated into muscle and mucosa, frozen under liquid nitrogen and stored at -80 °C for biochemical evaluation. The effect of H2O2 on the enzymes listed above was determined in the presence and absence of either resveratrol or a whole-grape suspension. (1) Resveratrol was significantly more effective than the grape suspension at protecting the bladder muscle and mucosa against peroxidation as quantitated by MDA formation. (2) The grape suspension was significantly more effective at protecting ChAT activity against oxidative stress of the muscle than resveratrol. (3) Neither the grape suspension nor resveratrol were particularly effective at protecting the bladder muscle or mucosa calcium ATPase or SERCA against oxidative stress. (4) ChAT was significantly more sensitive to oxidative stress than either calcium ATPase or SERCA. These data support the idea that the grape suspension protects the mitochondria and nerve terminals to a significantly greater degree than resveratrol which suggests that the activities of the grape suspension are due to the combination of active components found in the grape suspension and not just resveratrol alone.

  6. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway

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    Song Fu

    2018-02-01

    Full Text Available Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury. Spinal cord ischemia–reperfusion injury (IRI was performed by the infrarenal abdominal aorta with mini aneurysm clip model. The expressions of iNOS and p38MAPK and the levels of biochemical parameters, including nitrite/nitrate, malondialdehyde (MDA, advanced oxidation products (AOPP, reduced glutathione (GSH, superoxide dismutase (SOD and catalase (CAT were measured in control and experimental groups. IRI-induced rats treated with 10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by improved biological parameters measured in spinal cord tissue homogenates. The resveratrol treatment significantly decreased the levels of plasma nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK in IRI-induced rats. Further, IRI-produced free radicals were reduced by resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant levels such as GSH, SOD and CAT. Taken together, administration of resveratrol protects the damage caused by spinal cord ischemia with potential mechanism of suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of oxidative stress due to IRI.

  7. Effects of dietary supplementation of resveratrol on performance, egg quality, yolk cholesterol and antioxidant enzyme activity of laying hens.

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    Feng, Z H; Gong, J G; Zhao, G X; Lin, X; Liu, Y C; Ma, K W

    2017-10-01

    1. This experiment was conducted to evaluate the effects of dietary supplementation of resveratrol on laying performance, egg quality, egg yolk cholesterol and antioxidant enzyme activities of laying hens. 2. A total of 360 Beijing PINK-1 laying hens (60 weeks old) were randomly distributed among five dietary treatments, each of which included 6 replicates of 12 hens. Dietary treatments were basal diet supplemented with 0 (control), 0.5, 1.0, 2.0 and 4.0 g/kg diet resveratrol. The study lasted for 9 weeks including 1 week of adaptation and 8 weeks of the main experimental period. 3. The results indicated that dietary resveratrol significantly improved feed conversion ratios during 5-8 weeks and 1-8 weeks of the trial. Increasing dietary concentrations of the resveratrol linearly improved Haugh unit and albumen height of eggs. 4. The content of total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) in serum and cholesterol in yolk was significantly decreased by dietary resveratrol, and there were significant linear correlations between these indexes and resveratrol supplemental levels. 5. Dietary resveratrol supplementation significantly improved serum Glutathione peroxidase (GSH-Px) enzyme activity and decreased serum malondialdehyde (MDA) content in groups with 2.0 and 4.0 g/kg resveratrol as compared to the control, respectively. However, supplementation of resveratrol did not affect the activity of serum superoxide dismutase (SOD). 6. It is concluded that resveratrol supplementation has a positive effect on performance, lipid-related traits and antioxidant activity of laying hens.

  8. 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.

  9. Resveratrol

    DEFF Research Database (Denmark)

    Vang, Ole

    2015-01-01

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

  10. Resveratrol

    Science.gov (United States)

    ... skins, grape juice, wine, and other food sources. Wine should not be used as a source of resveratrol during pregnancy and breast-feeding. Bleeding disorders: Resveratrol might slow blood clotting and increase the ...

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

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    Albuquerque, Rosyana V; Malcher, Nívea S; Amado, Lílian L; Coleman, Michael D; Dos Santos, Danielle C; Borges, Rosivaldo Sa; Valente, Sebastião Aldo S; Valente, Vera C; Monteiro, Marta Chagas

    2015-01-01

    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.

  12. 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.

  13. Resveratrol, phenolic antioxidants, and saccharides in South American red wines

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    Osorio-Macías DE

    2018-01-01

    Full Text Available Daniel E Osorio-Macías,1,2 Pamela Vásquez,3 Cristhian Carrasco,3 Bjorn Bergenstahl,1 J Mauricio Peñarrieta2 1Department of Food Technology, Faculty of Engineering LTH, Lund University, Lund, Sweden; 2School of Chemistry, Faculty of Pure and Natural Sciences, 3Institute of Research and Development of Chemical Processes, Department of Chemical Engineering, Faculty of Engineering, Universidad Mayor de San Andrés (UMSA, La Paz, Bolivia Abstract: Wine is an important beverage with a long tradition, and its moderate consumption may be considered beneficial for human health. Although there are many studies regarding phenolic compounds in wines, there is a lack of information about antioxidants and phenolic content in South American wines. In this study, 35 South American red wines from four different countries, vintages 2004–2013, purchased at retail stores in La Paz, Bolivia, were studied. Resveratrol content, total antioxidant capacity (TAC by the 2,2′-azino-bis(3-ethylbenzotiazoline-6-sulfonic acid (ABTS and ferric-reducing antioxidant power (FRAP methods, total phenolic content (TPH, total flavonoids (TF, and main saccharides were assessed using the well-established spectrophotometric and high-performance liquid chromatography methods. The results ranged from 4 to 24 mmol/L for TAC determined by ABTS method and 14 to 43 mmol/L for TAC determined by FRAP method, 1600 to 3500 mg gallic acid equivalents/L for TPH, and 2 to 6 mmol catechin equivalents /L for TF. The resveratrol content ranged from 0.1 to 8 mg/L. Saccharides, glucose, and fructose content ranged from 0.4 to 10 g/L, 1.4 to 8.6 g/L, and 0.2 to 12 g/L, respectively. There was a high correlation among the different methods. The results showed that some wines growing at high altitude (>1500 meters above the sea level have higher amounts of TAC and phenolic content, including resveratrol, while non-varietal wines showed the lowest values. It was also observed that the saccharose

  14. The protective effect of resveratrols on ischaemia-reperfusion injuries of rat hearts is correlated with antioxidant efficacy

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    Hung, Li-Man; Su, Ming-Jai; Chu, Wing-Keung; Chiao, Chin-Wei; Chan, Wan-Fen; Chen, Jan-Kan

    2002-01-01

    Dietary antioxidants are thought to be beneficial in reducing the incidence of coronary heart disease. In this study, we compared resveratrol and analogues on their antioxidation and free radical scavenging activities to their protective effects on ischaemia-reperfusion induced injuries of rat hearts. Astringinin (3,3′,4′,5-tetrahydroxystilbene) was shown to be a more potent inhibitor than other analogues against Cu2+-induced LDL (low-density lipoprotein) oxidation, as measured by the formation of conjugated diene and TBARS (thiobarbituric acid-reactive substance) and by the electrophoretic mobility of the oxidized LDL. Resveratrol (trans-3,4′,5-trihydroxystilbene) and astringinin scavenged the stable free radical DPPH (1,1-diphenyl-2-picryl-hydrazyl) with an IC0.200 of 7.1 and 4.3 μM, respectively. Astringinin has a superoxide anion scavenging activity about 160 fold more potent than resveratrol. After a 30 min global ischemia followed by 2 h reperfusion, astringinin (10 μM) significantly reduced infarct size, superoxide anion production and increased functional recovery of the coronary flow in Langendorff-perfused rat hearts. The result showed there is a positive correlation between the anti-oxidation and cardioprotective activities among these phenolic compounds. Our finding together with the fact that astringinin is more water-soluble than resveratrol suggest that astringinin could potentially be used as an anti-oxidant and cardioprotective agent in biological systems. PMID:11934802

  15. Finding more active antioxidants and cancer chemoprevention agents by elongating the conjugated links of resveratrol.

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    Tang, Jiang-Jiang; Fan, Gui-Juan; Dai, Fang; Ding, De-Jun; Wang, Qi; Lu, Dong-Liang; Li, Ran-Ran; Li, Xiu-Zhuang; Hu, Li-Mei; Jin, Xiao-Ling; Zhou, Bo

    2011-05-15

    Resveratrol is the subject of intense research as a natural antioxidant and cancer chemopreventive agent. There has been a great deal of interest and excitement in understanding its action mechanism and developing analogs with antioxidant and cancer chemoprevention activities superior to that of the parent compound in the past decade. This work delineates that elongation of the conjugated links is an important strategy to improve the antioxidant activity of resveratrol analogs, including hydrogen atom- or electron-donating ability in homogeneous solutions and antihemolysis activity in heterogeneous media. More importantly, C3, a triene bearing 4,4'-dihydroxy groups, surfaced as an important lead compound displaying remarkably increased antioxidant, cytotoxic, and apoptosis-inducing activities compared with resveratrol. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats.

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    Xu, Dunquan; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro . The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro , suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study

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

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    Lançon, Allan; Frazzi, Raffaele; Latruffe, Norbert

    2016-03-02

    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.

  18. 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.

  19. The Grape Antioxidant Resveratrol for Skin Disorders: Promise, Prospects, and Challenges

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    Ndiaye, Mary; Philippe, Carol; Mukhtar, Hasan; Ahmad, Nihal

    2011-01-01

    Resveratrol, a phytoalexin antioxidant found in red grapes, has been shown to have both chemopreventive and therapeutic effects against many diseases and disorders, including those of the skin. Studies have shown protective effects of resveratrol against ultraviolet radiation mediated oxidative stress and cutaneous damages including skin cancer. Because many of the skin conditions stem from ultraviolet radiation and oxidative stress, this antioxidant appears to have promise and prospects against a wide range of cutaneous disorders including skin aging and skin cancers. However, there are a few roadblocks in the way of this promising agent regarding its translation from the bench to the bedside. This review discusses the promise and prospects of resveratrol in the management of skin disorders and the associated challenges. PMID:21215251

  20. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

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    Bath, Sundeep

    2015-01-01

    Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

  1. Nanodesign of olein vesicles for the topical delivery of the antioxidant resveratrol.

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    Pando, Daniel; Caddeo, Carla; Manconi, Maria; Fadda, Anna Maria; Pazos, Carmen

    2013-08-01

    The ex-vivo percutaneous absorption of the natural antioxidant resveratrol in liposomes and niosomes was investigated. The influence of vesicle composition on their physicochemical properties and stability was evaluated. Liposomes containing resveratrol were formulated using soy phosphatidylcholine (Phospholipon90G). Innovative niosomes were formulated using mono- or diglycerides: glycerol monooleate (Peceol) and polyglyceryl-3 dioleate (Plurol OleiqueCC), respectively, two suitable skin-compatible oleins used in pharmaceutical formulations as penetration enhancers. Small, negatively charged vesicles with a mean size of approximately 200 nm were prepared. The accelerated stability of vesicles was evaluated using Turbiscan Lab Expert, and the bilayer deformability was also assessed. Ex-vivo transdermal experiments were carried out in Franz diffusion cells, on newborn pig skin, to study the influence of the different vesicle formulations on resveratrol skin delivery. Results indicated a high cutaneous accumulation and a low transdermal delivery of resveratrol, especially when Peceol niosomes were used. Overall, niosomes formulated with Plurol oleique or Peceol showed a better behaviour than liposomes in the cutaneous delivery of resveratrol. © 2013 Royal Pharmaceutical Society.

  2. Resveratrol and Red Wine Function as Antioxidants in the Nervous System without Cellular Proliferative Effects during Experimental Diabetes

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    Venturini, Carina Duarte; Merlo, Suélen; Souto, André Arigony; Fernandes, Marilda da Cruz; Gomez, Rosane; Rhoden, Claudia Ramos

    2010-01-01

    Chronic hyperglycemia increases oxidative stress status and has been associated with neurological complications in diabetic individuals. This study compared the antioxidant properties of red wine or resveratrol in different brain areas of diabetic and non-diabetic rats, and investigated the effect of them on hippocampal cell proliferation in hippocampal dentate gyrus of diabetic rats. Streptozotocin-induced diabetic and control rats were treated with red wine (4 mL/kg), resveratrol (20 mg/kg) or saline, by oral gavage, for 21 days. Lipid peroxidation (TBARS), catalase and superoxide dismutase were measured to evaluate the oxidative stress and the BrdU-positive cells were assessed to measure changes in cellular proliferation. In diabetic animals, resveratrol showed antioxidant property in the hippocampus and in the striatum, while red wine had an antioxidant effect only in the hippocampus. Neither red wine nor resveratrol reversed the lower hippocampal cell proliferation in diabetic rats. Daily doses of red wine or resveratrol have an antioxidant effect in rats depending on the brain area and the glycemic status. PMID:21307644

  3. Resveratrol and Red Wine Function as Antioxidants in the Nervous System without Cellular Proliferative Effects during Experimental Diabetes

    Directory of Open Access Journals (Sweden)

    Carina Duarte Venturini

    2010-01-01

    Full Text Available Chronic hyperglycemia increases oxidative stress status and has been associated with neurological complications in diabetic individuals. This study compared the antioxidant properties of red wine or resveratrol in different brain areas of diabetic and non-diabetic rats, and investigated the effect of them on hippocampal cell proliferation in hippocampal dentate gyrus of diabetic rats. Streptozotocin-induced diabetic and control rats were treated with red wine (4 mL/kg, resveratrol (20 mg/kg or saline, by oral gavage, for 21 days. Lipid peroxidation (TBARS, catalase and superoxide dismutase were measured to evaluate the oxidative stress and the BrdU-positive cells were assessed to measure changes in cellular proliferation. In diabetic animals, resveratrol showed antioxidant property in the hippocampus and in the striatum, while red wine had an antioxidant effect only in the hippocampus. Neither red wine nor resveratrol reversed the lower hippocampal cell proliferation in diabetic rats. Daily doses of red wine or resveratrol have an antioxidant effect in rats depending on the brain area and the glycemic status.

  4. Resveratrol-Inspired Benzo[b]selenophenes Act as Anti-Oxidants in Yeast

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    Dominika Mániková

    2018-02-01

    Full Text Available Resveratrol is a natural (polyphenol primarily found in plants protecting them against pathogens, as well as harmful effects of physical and chemical agents. In higher eukaryotic cells and organisms, this compound displays a remarkable range of biological activities, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, cardio- and neuro-protective properties. Here, biological activities of synthetic selenium-containing derivatives of resveratrol—benzo[b]selenophenes—have been studied in lower eukaryotes Saccharomyces cerevisiae. Their toxicity, as well as DNA damaging and reactive oxygen species (ROS inducing potencies, manifested through their ability to act as redox active anti-microbial agents, have been examined. We show that some benzo[b]selenophenes can kill yeast cells and that the killing effects are not mediated by DNA damage types that can be detected as DNA double-strand breaks. These benzo[b]selenophenes could potentially be used as anti-fungal agents, although their concentrations relevant to application in humans need to be further evaluated. In addition, most of the studied benzo[b]selenophenes display redox-modulating/anti-oxidant activity (comparable or even higher than that of resveratrol or Trolox causing a decrease in the intracellular ROS levels in yeast cells. Therefore, after careful re-evaluation in other biological systems these observations might be transferred to humans, where resveratrol-inspired benzo[b]selenophenes could be used as supra-anti-oxidant supplements.

  5. Antioxidant capacity of trans-resveratrol dietary supplements alone or combined with the mycotoxin beauvericin.

    Science.gov (United States)

    Mallebrera, Beatriz; Maietti, Annalisa; Tedeschi, Paola; Font, Guillermina; Ruiz, Maria-Jose; Brandolini, Vincenzo

    2017-07-01

    Trans-resveratrol (trans-RSV) is a polyphenol with multiples biological properties, such as anti-inflammatory, antioxidant, anti-aging, anti-diabetic, and antiplatelet. It occurs naturally in grapes and derivate, peanuts and berries. Beauvericin (BEA) is a mycotoxin present in cereals that produces cytotoxicity, intracellular reactive oxygen species and lipid peroxidation. The general objective of this research was to evaluate whether trans-RSV could be used as a good polyphenol against damages produced by BEA. Because trans-RSV can be ingested through dietary supplements, to reach this goal, the following specific objectives were proposed: to determine a) the trans-RSV content in different polyphenol dietary supplements by capillary electrophoresis, b) the antioxidant capacity of the trans-RSV in polyphenol supplements, and c) the influence of BEA in the antioxidant capacity of trans-RSV when they are in combination by photochemioluminiscence assay. The results obtained in this study showed that all polyphenol dietary supplements present higher RSV content that the content of the label. The polyphenol supplements present antioxidant capacity. And the combination of trans-RSV and BEA did not affect the antioxidant capacity of trans-RSV. Thus, RSV could contribute to decrease oxidant effects produced by BEA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Therapeutic Versatility of Resveratrol Derivatives

    OpenAIRE

    Waqas Nawaz; Zhongqin Zhou; Sa Deng; Xiaodong Ma; Xiaochi Ma; Chuangang Li; Xiaohong Shu

    2017-01-01

    Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol to enhance the bioavailability and the pharmacological activity of resveratrol. During the past decades, a large number of natural a...

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

    Science.gov (United States)

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

    2016-03-01

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

  9. Resveratrol and liver: A systematic review.

    Science.gov (United States)

    Faghihzadeh, Forouzan; Hekmatdoost, Azita; Adibi, Payman

    2015-08-01

    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. 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. 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. 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.

  10. 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.

  11. Antioxidant activity and photostability assessment of trans-resveratrol acrylate microspheres.

    Science.gov (United States)

    Pignatello, Rosario; Pecora, Tiziana M G; Cutuli, Giuseppa G; Catalfo, Alfio; De Guidi, Guido; Ruozi, Barbara; Tosi, Giovanni; Cianciolo, Simona; Musumeci, Teresa

    2018-03-22

    Trans-resveratrol (RSV) was microencapsulated in Eudragit ® RS100 and RL100 resin blends. Lyophilized microspheres were characterized in the solid state for their micromeritic properties and drug loading. FT-IR, PXRD and DSC analyses suggested that RSV formed an intimate microcrystalline dispersion within the polymer network, also confirmed by SEM analysis. This produced a reduced degradation of RSV after storage at 40°C, compared to the neat drug, and a protection of the drug from UV light-induced trans-cis isomerization (60% intact drug was found after 60 sec irradiation at 350 nm, compared to 37% for the pure drug). Solubility and in vitro dissolution studies indicated that microencapsulation did not improve the dissolution pattern of RSV in simulated gastric and intestinal aqueous fluids. Evaluation of the in vitro antioxidant activity showed that, compared to the neat drug in aqueous solution, RSV loaded in the microspheres retained for a longer time, up to 22 days of incubation, the initial ORAC capacity. The present study thus demonstrated that Eudragit ® Retard resins can be used to easily produce micro-sized solid dispersions with RSV, for potential oral administration, contributing to ameliorate the physico-chemical stability and antioxidant activity of this compound.

  12. Testing of resveratrol microemulsion photostability and protective effect against UV induced oxidative stress

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    Juškaitė Vaida

    2017-06-01

    Full Text Available Resveratrol is well known for its antioxidant activity and susceptibility to ultraviolet radiation. Development of formulations providing improved stability and relevant drug delivery of resveratrol is still a challenging task. The aim of this study was to determine protective characteristics of formulated microemulsions by evaluating photoisomerization of resveratrol and to investigate the effects of resveratrol on human keratinocyte cells under oxidative stress caused by ultraviolet radiation. Incorporation of resveratrol into microemulsions resulted in increased photostability of active compounds and the results demonstrated that photodegradation of resveratrol was significantly delayed. Results of biopharmaceutical evaluation in vitro demonstrated that up to 60 % of resveratrol was released from microemulsions within 6 hours under a constant release rate profile. In vivo biological testing confirmed the ability of resveratrol to protect cells from oxidative stress and to increase cell viability. It was concluded that microemulsions might be considered in the development of UV light sensitive compounds.

  13. Resveratrol and Myopathy

    OpenAIRE

    Jean Bastin; Fatima Djouadi

    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 ?-oxidation or oxidative ph...

  14. Synergistic effects of resveratrol (free and inclusion complex) and sulfamethoxazole-trimetropim treatment on pathology, oxidant/antioxidant status and behavior of mice infected with Toxoplasma gondii.

    Science.gov (United States)

    Bottari, Nathieli B; Baldissera, Matheus D; Tonin, Alexandre A; Rech, Virginia C; Alves, Catiane B; D'Avila, Fernanda; Thomé, Gustavo R; Guarda, Naiara S; Moresco, Rafael N; Camillo, Giovana; Vogel, Fernanda F; Luchese, Cristiane; Schetinger, Maria Rosa C; Morsch, Vera M; Tochetto, Camila; Fighera, Rafael; Nishihira, Vivian S K; Da Silva, Aleksandro S

    2016-06-01

    This study aimed to investigate the synergistic effects of resveratrol and sulfamethoxazole-trimethoprim (ST) on the treatment of mice experimentally infected by Toxoplasma gondii during the chronic phase of the disease considering infection, behavior, and oxidative/antioxidants profile aspects. For the study, 60 mice were initially divided into two groups: uninfected (n = 24) and infected by T. gondii (n = 36). These two groups were later subdivided into other groups and treated with resveratrol (free and inclusion complex containing resveratrol) alone and co-administered with ST: groups A to D were composed by healthy mice and groups E to J were consisted of animals infected by T. gondii (VEG strain). Treatments began 20 days post-infection for 10 consecutive days with oral doses of 0.5 mg kg(-1) of ST (groups B and F), 100 mg kg(-1) of free resveratrol (groups C and G) and inclusion complex of resveratrol (nanoparticles containing resveratrol) (groups D and H), and lastly an co-administration of both drugs (groups I and J). Behavioral tests (memory, anxiety and locomotion) were performed after treatment. Liver and brain fragments were collected to evaluate pathological changes, brain cysts counts, as well as oxidant and antioxidant levels. A reduction on the number of cysts in the brain of animals treated with both drugs combined was observed; there was also reduced number of lesions on both organs. This drug combined effect was also able to reduce oxidative and increase antioxidant levels in infected mice, which might be interpreted as a resveratrol protective effect. In addition, the combination of ST and resveratrol was able to prevent behavioral changes in infected mice. Therefore, the use of co-administration drugs enhances the therapeutic effect acting on a synergic way, reducing the oxidizing effects of the chemical treatment for toxoplasmosis. In addition, resveratrol in inclusion complex when co-administered with ST showed an improved

  15. Resveratrol for patients with chronic obstructive pulmonary disease: hype or hope?

    Science.gov (United States)

    Beijers, Rosanne J H C G; Gosker, Harry R; Schols, Annemie M W J

    2018-03-01

    Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with a high prevalence of extrapulmonary manifestations and, frequently, cardiovascular comorbidity. Resveratrol is a food-derived compound with anti-inflammatory, antioxidant, metabolic and cardioprotective potential. Therefore, resveratrol might improve the pulmonary as well as extrapulmonary pathology in COPD. In this review, we will evaluate knowledge on the effects of resveratrol on lung injury, muscle metabolism and cardiovascular risk profile and discuss if resveratrol is a hype or hope for patients with COPD. Experimental models of COPD consistently show decreased inflammation and oxidative stress in the lungs after resveratrol treatment. These beneficial anti-inflammatory and antioxidant properties of resveratrol can indirectly also improve both skeletal and respiratory muscle impairment in COPD. Recent clinical studies in non-COPD populations show improved mitochondrial oxidative metabolism after resveratrol treatment, which could be beneficial for both lung and muscle impairment in COPD. Moreover, preclinical studies suggest cardioprotective effects of resveratrol but results of clinical studies are inconclusive. Resveratrol might be an interesting therapeutic candidate to counteract lung and muscle impairments characteristic to COPD. However, there is no convincing evidence that resveratrol will significantly decrease the cardiovascular risk in patients with COPD.

  16. 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.

  17. Biocatalysis and biotransformation of resveratrol in microorganisms.

    Science.gov (United States)

    Mei, Yan-Zhen; Liu, Ruo-Xue; Wang, Dong-Peng; Wang, Xia; Dai, Chuan-Chao

    2015-01-01

    Resveratrol, a major stilbene phytoalexin, is a valuable polyphenol that has been recognized for its benefits to human health. Resveratrol has antioxidant and antitumor effects and promotes longevity. It is used in medicine, health care products, cosmetics, and other industries. Therefore, a sustainable source for resveratrol production is required. This review describes the metabolic engineering of microorganisms, the biotransformation and biosynthesis of endophytes and the oxidation or degradation of resveratrol. We compare various available methods for resveratrol production, and summarize the practical challenges facing the microbial production of resveratrol. The future research direction for resveratrol is also discussed.

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

    Directory of Open Access Journals (Sweden)

    Shraddha D. Rege

    2013-01-01

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

  19. Resveratrol, pterostilbene, and dementia.

    Science.gov (United States)

    Lange, Klaus W; Li, Shiming

    2018-01-01

    Resveratrol is a natural phytoestrogen with neuroprotective properties. Polyphenolic compounds including resveratrol exert in vitro antioxidant, anti-inflammatory, and antiamyloid effects. Resveratrol and its derivative pterostilbene are able to cross the blood-brain barrier and to influence brain activity. The present short review summarizes the available evidence regarding the effects of these polyphenols on pathology and cognition in animal models and human subjects with dementia. Numerous investigations in cellular and mammalian models have associated resveratrol and pterostilbene with protection against dementia syndromes such as Alzheimer's disease (AD) and vascular dementia. The neuroprotective activity of resveratrol and pterostilbene demonstrated in in vitro and in vivo studies suggests a promising role for these compounds in the prevention and treatment of dementia. In comparison to resveratrol, pterostilbene appears to be more effective in combatting brain changes associated with aging. This may be attributed to the more lipophilic nature of pterostilbene with its two methoxyl groups compared with the two hydroxyl groups of resveratrol. The findings of available intervention trials of resveratrol in individuals with mild cognitive impairment or AD do not provide evidence of neuroprotective or therapeutic effects. Future clinical trials should be conducted with long-term exposure to preparations of resveratrol and pterostilbene with high bioavailability. © 2017 BioFactors, 44(1):83-90, 2018. © 2017 International Union of Biochemistry and Molecular Biology.

  20. Isolation, characterization, spectroscopic properties and quantum chemical computations of an important phytoalexin resveratrol as antioxidant component from Vitis labrusca L. and their chemical compositions

    Science.gov (United States)

    Güder, Aytaç; Korkmaz, Halil; Gökce, Halil; Alpaslan, Yelda Bingöl; Alpaslan, Gökhan

    2014-12-01

    In this study, isolation and characterization of trans-resveratrol (RES) as an antioxidant compound were carried out from VLE, VLG and VLS. Furthermore, antioxidant activities were evaluated by using six different methods. Finally, total phenolic, flavonoid, ascorbic acid, anthocyanin, lycopene, β-carotene and vitamin E contents were carried out. In addition, the FT-IR, 13C and 1H NMR chemical shifts and UV-vis. spectra of trans-resveratrol were experimentally recorded. Quantum chemical computations such as the molecular geometry, vibrational frequencies, UV-vis. spectroscopic parameters, HOMOs-LUMOs energies, molecular electrostatic potential (MEP), natural bond orbitals (NBO) and nonlinear optics (NLO) properties of title molecule have been calculated by using DFT/B3PW91 method with 6-311++G(d,p) basis set in ground state for the first time. The obtained results show that the calculated spectroscopic data are in a good agreement with experimental data.

  1. Therapeutic Versatility of Resveratrol Derivatives.

    Science.gov (United States)

    Nawaz, Waqas; Zhou, Zhongqin; Deng, Sa; Ma, Xiaodong; Ma, Xiaochi; Li, Chuangang; Shu, Xiaohong

    2017-10-29

    Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol to enhance the bioavailability and the pharmacological activity of resveratrol. During the past decades, a large number of natural and synthetic resveratrol derivatives were extensively studied, and the methoxylated, hydroxylated and halogenated derivatives of resveratrol received particular more attention for their beneficial bioactivity. So, in this review, we will summarize the chemical structure and the therapeutic versatility of resveratrol derivatives, and thus provide the related structure activity relationship reference for their practical applications.

  2. Resveratrol Prevents Diabetic Cardiomyopathy by Increasing Nrf2 Expression and Transcriptional Activity

    Directory of Open Access Journals (Sweden)

    Guan Wang

    2018-01-01

    Full Text Available Objective. This study investigated if resveratrol ameliorates diabetic cardiomyopathy by targeting associated oxidative stress mechanisms. Method. Type 1 diabetes mellitus (DM in FVB mice was induced by several intraperitoneal injections of a low dose of streptozotocin. Hyperglycemic and age-matched control mice were given resveratrol (10 mg/kg per day for 1 month and subsequently monitored for an additional 6 months. Mice were assigned to four groups: control, resveratrol, DM, and DM/resveratrol. Cardiac function and blood pressure were assessed at 1, 3, and 6 months after DM induction. Oxidative damage and cardiac fibrosis were analyzed by histopathology, real-time PCR, and Western blot. Result. Mice in the DM group exhibited increased blood glucose levels, cardiac dysfunction, and high blood pressure at 1, 3, and 6 months after DM induction. Resveratrol did not significantly affect blood glucose levels and blood pressure; however, resveratrol attenuated cardiac dysfunction and hypertrophy in DM mice. Resveratrol also reduced DM-induced fibrosis. In addition, DM mice hearts exhibited increased oxidative damage, as evidenced by elevated accumulation of 3-nitrotyrosine and 4-hydroxynonenal, which were both attenuated by resveratrol. Mechanistically, resveratrol increased NFE2-related factor 2 (Nrf2 expression and transcriptional activity, as well as Nrf2’s downstream antioxidative targets. Conclusion. We demonstrated that resveratrol prevents DM-induced cardiomyopathy, in part, by increasing Nrf2 expression and transcriptional activity.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  4. Resveratrol and its biological actions

    OpenAIRE

    Shah Praharsh; Patel Jagruti

    2010-01-01

    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, exhibiti...

  5. 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...... of red wine. Resveratrol has also been produced by chemical synthesis or by biotechnological synthesis and is sold as a nutritional supplement derived primarily from Japanese knotweed....

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/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 (E 2 ) biosynthesis and enhancing metabolic clearance of E 2 , increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E 2 levels by inhibiting hydroxylation, glucuronidation and sulphation of E 2 . This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of estradiol in the

  7. 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.

  8. Resveratrol and cancer: Challenges for clinical translation.

    Science.gov (United States)

    Singh, Chandra K; Ndiaye, Mary A; Ahmad, Nihal

    2015-06-01

    Significant work has been done towards identifying the health-beneficial effects of the grape antioxidant resveratrol in a variety of bioassay- and disease- models, with much research being focused on its possible application to cancer management. Despite the large number of preclinical studies dealing with different aspects of the biological effects of resveratrol, its translation to clinics is far from reality due to a variety of challenges. In this review, we discuss the issues and questions associated with resveratrol becoming an effective in vivo anticancer drug, from basic metabolic issues to the problems faced by incomplete understanding of the mechanism(s) of action in the body. We also explore efforts taken by researchers, both public and private, to contend with some of these issues. By examining the published data and previous clinical trials, we have attempted to identify the problems and issues that hinder the clinical translation of resveratrol for cancer management. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Resveratrol Oligomers for the Prevention and Treatment of Cancers

    OpenAIRE

    Xue, You-Qiu; Di, Jin-Ming; Luo, Yun; Cheng, Ke-Jun; Wei, Xing; Shi, Zhi

    2014-01-01

    Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest ...

  10. Resveratrol and Myopathy.

    Science.gov (United States)

    Bastin, Jean; Djouadi, Fatima

    2016-04-28

    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.

  11. 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

  12. Resveratrol and Myopathy

    Directory of Open Access Journals (Sweden)

    Jean Bastin

    2016-04-01

    Full Text Available 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.

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

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

    2014-10-15

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

  14. Resveratrol inhibits LPS-induced mice mastitis through attenuating the MAPK and NF-κB signaling pathway.

    Science.gov (United States)

    Zhang, Xu; Wang, Yanan; Xiao, Chong; Wei, Zhengkai; Wang, Jingjing; Yang, Zhengtao; Fu, Yunhe

    2017-06-01

    Resveratrol is a natural polyphenol extracted from mangy plants. It has been reported that resveratrol show multitudinous positive role in biology such as anti-oxidant, anti-nociception and anti-inflammatory effects. Therefore, the present study devotes to test the effect of resveratrol on LPS-induced mastitis in mice. Resveratrol was administered intraperitoneally 1 h before LPS treatment. And the anti-inflammatory effect of resveratrol was measured by histopathological examination, MPO assay, real-time PCR and western blotting analysis. The results showed that resveratrol significantly reduced the LPS-induced mammary histopathological changes. Meanwhile, it sharply attenuated the activity of MPO. The result also indicated that the resveratrol can decrease the expression of pro-inflammatory cytokines TNF-α and IL-1β. From the results of western blotting, resveratrol suppressed the expression of phosphorylation of p65 and IκB from NF-κB signal pathway and phosphorylation of p38 and ERK from MAPK signal pathway. These findings suggested that resveratrol may inhibit the inflammatory response in the mastitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Resveratrol and Brain Mitochondria: a Review.

    Science.gov (United States)

    Jardim, Fernanda Rafaela; de Rossi, Fernando Tonon; Nascimento, Marielle Xavier; da Silva Barros, Renata Gabriele; Borges, Paula Agrizzi; Prescilio, Isabella Cristina; de Oliveira, Marcos Roberto

    2018-03-01

    Resveratrol (3,4',5-trihydroxystilbene; C 14 H 12 O 3 ) is a polyphenolic phytoalexin found in grapes, berries, peanuts, and wines. Resveratrol has been viewed as an antioxidant, anti-inflammatory, anti-apoptotic, and anticancer agent. Moreover, it has been reported that resveratrol modulates mitochondrial function, redox biology, and dynamics in both in vitro and in vivo experimental models. Resveratrol also attenuates mitochondrial impairment induced by certain stressors. Resveratrol upregulates, for example, mitochondria-located antioxidant enzymes, decreasing the production of reactive species by these organelles. Resveratrol also triggers mitochondrial biogenesis, ameliorating the mitochondria-related bioenergetics status in mammalian cells. In the present work, we discuss about the effects of resveratrol on brain mitochondria. Brain cells (both neuronal and glial) are susceptible to mitochondrial dysfunction due to their high demand for adenosine triphosphate (ATP). Additionally, brain cells consume oxygen (O 2 ) at very high rates, leading to a proportionally high mitochondrial production of reactive species. Therefore, strategies focusing on the maintenance of mitochondrial function in these cell types are of pharmacological interest in the case of neurodegenerative diseases, which involve mitochondrial impairment and increased generation of reactive species, leading to neuroinflammation and cell death. The mechanism by which resveratrol protects mitochondrial function and dynamics is not completely understood, and further research would be necessary in order to investigate exactly how resveratrol affects mitochondria-related parameters. Furthermore, it is particularly important because resveratrol is able to induce cytotoxicity depending on its dosage.

  16. The Repeated Administration of Resveratrol Has Measurable Effects on Circulating T-Cell Subsets in Humans

    Directory of Open Access Journals (Sweden)

    J. Luis Espinoza

    2017-01-01

    Full Text Available Preclinical studies have shown that resveratrol exerts immunomodulatory effects with potential clinical value in the amelioration of autoimmune disorders and cancer prevention; however, little is known about the in vivo effects of this naturally occurring polyphenol on human immune cells. We assessed the effects of repeated doses of resveratrol (1000 mg/day for 28 days on circulating immune cells in healthy Japanese individuals. Resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating γδ T cells and regulatory T cells and resulted in small, yet significant, decreases in the plasma levels of the proinflammatory cytokines TNF-α and MCP-1 and a significant increase in the plasma antioxidant activity compared with the corresponding antioxidant baseline activity and with that in four control individuals. In in vitro studies, resveratrol significantly improved the growth of γδ T cells and regulatory T cells. These findings demonstrate that resveratrol has some clear biological effects on human circulating immune cells. Further studies are necessary to interpret the long-term immunological changes associated with resveratrol treatment.

  17. Effect of artificial ageing using different wood chips on the antioxidant activity, resveratrol and catechin concentration, sensory properties and colour of two Greek red wines.

    Science.gov (United States)

    Gortzi, Olga; Metaxa, Xenia; Mantanis, George; Lalas, Stavros

    2013-12-01

    Two Greek red wines (Syrah and Cabernet) were artificially aged with different wood chips (white oak, red oak, Turkey oak, chestnut, Bosnian pine, cherry, common juniper, common walnut, white mulberry, black locust and apricot). The influence of each wood species was tested for up to 20 days. The optimum duration for the extraction of total polyphenols was 20 days (Syrah) or 10 days (Cabernet) when chips of white oak, chestnut, cherry, white mulberry, black locust and apricot where used. Resveratrol and catechin concentrations ranged within the limits previously reported in literature. A high antioxidant activity was established after 10 days of artificial ageing. The sensory evaluation showed that the best results were produced by the apricot chips after 5 days (Syrah) or black locust and apricot after 5 days (Cabernet). Colour was seen to increase with both time of ageing and number of wood chips added. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Resveratrol and liver: A systematic review

    OpenAIRE

    Forouzan Faghihzadeh; Azita Hekmatdoost; Payman Adibi

    2015-01-01

    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...

  19. Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response, and Longevity-Related Gene Expression in Drosophila melanogaster

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    Stefanie Staats

    2018-01-01

    Full Text Available In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster. Male and female w1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant (catalase, glutathione-S-transferase, NADH dehydrogenase, glutathione peroxidase, superoxide dismutase 2 and longevity-related genes, including sirtuin 2, spargel, and I’m Not Dead Yet. Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w1118 D. melanogaster.

  20. The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation.

    Directory of Open Access Journals (Sweden)

    Chao-Bin Yeh

    Full Text Available The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC. Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion.Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol.Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways.

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

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    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.

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

    International Nuclear Information System (INIS)

    Sebastia, Natividad; Montoro, Alegria; Montoro, Amparo; Almonacid, Miguel; Villaescusa, Juan Ignacio; Cervera, Jose; Such, Esperanza; Silla, Ma Angeles; Soriano, Jose Miguel

    2011-01-01

    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.

  3. Effect of resveratrol on cognitive and memory performance and mood: A meta-analysis of 225 patients.

    Science.gov (United States)

    Farzaei, Mohammad Hosein; Rahimi, Roja; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2018-02-01

    Resveratrol is a natural dietary phenolic compound which is extensively present in many edible fruits, including grape, berries, pomegranates, and peanuts. Reseveratrol has a broad spectrum of biological activities including anti-aging, chemopreventive, anti-carcinogenic, anti-inflammatory and antioxidant effects and thus it is effective in related diseases. Particularly, the positive effects of resveratrol in neuropsychological diseases have been proven in in-vitro and in-vivo studies. Some clinical trials have reported that resveratrol possesses preventive and therapeutic effects in cognitive disorders. Therefore, the current systematic review and meta-analysis aimed to assess the effects of resveratrol on cognition and memory performance as well as mood state. Electronic databases including Scopus, PubMed, Science Direct, and Cochrane library were searched with the keywords "Memory", "Cognitive", "Cognition" or "Mood" with "Resveratrol" until June 2017. Only clinical studies were included in this review. We have provided the most reliable evidence to date counting results obtained from 226 individuals from four randomized clinical trials evaluating the mentioned specific effects of resveratrol. The results of this meta-analysis showed that resveratrol has no significant effect on memory and cognitive performance assessed by auditory verbal learning tests. Two parameters of Profile of Mood States (POMS) including vigor and fatigue, decreased significantly by resveratrol. However, decrease in other parameters of POMS including tense/anxiety, depression, anger, and confusion by resveratrol was not significant. The key findings from this meta-analysis are that resveratrol has no significant impact on factors related to memory and cognitive performance, including learning ability, delayed recall, retention, and recognition with all effect sizes non-significant and effectively at zero. However, it has the potential to enhance mood. Further randomized, controlled

  4. 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

  5. Resveratrol-Loaded Polymeric Nanoparticles: Validation of an HPLC-PDA Method to Determine the Drug Entrapment and Evaluation of Its Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Gabriela da Rocha Lindner

    2013-01-01

    Full Text Available Poly(lactic acid (PLA and PLA-poly(ethylene glycol (PLA-PEG nanoparticles containing resveratrol (RVT were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC/photodiode array (PDA detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm, and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles containing RVT were evaluated for their ability to scavenge the radical (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS•+. The profile obtained from the PLA nanoparticles containing RVT demonstrated that after 24 h, there was almost no increase in antioxidant activity, which was lower than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG nanoparticles, the radical-scavenging activity of RVT was shown to increase with time, and after 48 h, it was similar to that observed with free RVT.

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

    Science.gov (United States)

    de Ligt, Marlies; Timmers, Silvie; Schrauwen, Patrick

    2015-06-01

    There is an increasing need for novel preventive and therapeutic strategies to combat obesity and related metabolic disorders. In this respect, the natural polyphenol resveratrol has attracted significant interest. Animal studies indicate that resveratrol mimics the effects of calorie restriction via activation of sirtuin 1 (SIRT1). SIRT1 is an important player in the regulation of cellular energy homeostasis and mitochondrial biogenesis. Rodent studies have shown beneficial effects of resveratrol supplementation on mitochondrial function, glucose metabolism, body composition and liver fat accumulation. However, confirmation of these beneficial effects in humans by placebo-controlled clinical trials remains relatively limited. This review will give an overview of pre-clinical and clinical studies examining the effects of resveratrol on obesity-induced negative health outcomes. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Braga, Adelaide; Oliveira, Joana; Silva, Rita; Ferreira, Patricia; Rocha, Isabel; Kallscheuer, Nicolai; Marienhagen, Jan; Faria, Nuno

    2018-01-10

    The health benefits of polyphenols such as stilbenes and flavonoids for humans are increasingly attracting attention. Resveratrol is a well-characterized naturally-occurring stilbene and potent anti-oxidant, which is used as food supplement and cosmetic ingredient. Several microorganisms including Corynebacterium glutamicum were engineered for resveratrol production from glucose. Based on the cultivation of a resveratrol-producing C. glutamicum strain in shake flasks, different strategies for improving production under controlled conditions at bioreactor scale were tested. To this end, different cultivation parameters including substrate concentration and operation modes (batch and fed-batch) were evaluated. Whereas the highest biomass concentration was observed during fed-batch fermentation, the maximum resveratrol production was achieved in batch mode. The maximal titer obtained was 12mgL -1 of resveratrol without the addition of the fatty acid synthase inhibitor cerulenin, which was previously shown to be crucial for production with C. glutamicum. The specific growth rate during production seems to have a significant effect in resveratrol production and apparently low specific growth rates may redirect the metabolic bottleneck from p-coumaric acid formation to malonyl-CoA or ATP availability. We also show that high oxygen concentrations in the bioreactor negatively affected the obtained resveratrol titers with C. glutamicum, which is most likely due to the strong tendency of resveratrol to oxidize or oligomerize. Thus, up-scaling of the resveratrol production process is technically challenging and individual process parameters have to be optimized cautiously. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The Role of Resveratrol in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jeong-Hyeon Ko

    2017-12-01

    Full Text Available Abstract: Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Compounds that modulate these oncogenic processes can be considered as potential anti-cancer agents that may ultimately make it to clinical application. Resveratrol, a natural stilbene and a non-flavonoid polyphenol, is a phytoestrogen that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. It has been reported that resveratrol can reverse multidrug resistance in cancer cells, and, when used in combination with clinically used drugs, it can sensitize cancer cells to standard chemotherapeutic agents. Several novel analogs of resveratrol have been developed with improved anti-cancer activity, bioavailability, and pharmacokinetic profile. The current focus of this review is resveratrol’s in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol. This is also accompanied by a comprehensive update of the various clinical trials that have demonstrated it to be a promising therapeutic and chemopreventive agent.

  9. Resveratrol: A potential challenger against gastric cancer

    Science.gov (United States)

    Zulueta, Aida; Caretti, Anna; Signorelli, Paola; Ghidoni, Riccardo

    2015-01-01

    Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor. Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori (H. pylori) are the major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent. Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here. PMID:26457023

  10. Resveratrol immobilization and release in polymeric hydrogels

    International Nuclear Information System (INIS)

    Momesso, Roberta Grazzielli Ramos Alves Passarelli

    2010-01-01

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

  11. Resveratrols in grape berry skins and leaves in vitis germplasm.

    Science.gov (United States)

    Wang, Lijun; Xu, Man; Liu, Chunyan; Wang, Junfang; Xi, Huifen; Wu, Benhong; Loescher, Wayne; Duan, Wei; Fan, Peige; Li, Shaohua

    2013-01-01

    Resveratrol is an important stilbene that benefits human health. However, it is only distributed in a few species including grape and is very expensive. At present, grape has been an important source resveratrol. However, the details are scarce on resveratrol distribution in different Vitis species or cultivars. The composition and content of resveratrols were investigated by HPLC for assessing genotypic variation in berry skins and leaves of 75 grape cultivars, belonging to 3 species and 7 interspecific hybrids. Trans-resveratrol, cis-piceid and trans-piceid were detected in berry skins and leaves, but cis-resveratrol was not. Resveratrol content largely varied with genetic background as well as usage. In most cultivars, total resveratrol including the above three compounds was higher in berry skins than leaves. In berry skins of most cultivars and leaves of almost all cultivars, cis-piceid was the most abundant resveratrol; trans-resveratrol and trans-piceid were minor components. Some specific cultivars were found with extremely high levels of trans-resveratrol, cis- piceid, trans-piceid or total resveratrols in berry skins or leaves. In skins and leaves, rootstock cultivars had a higher content of total resveratrols, and the cultivated European type cultivars and their hybrids with V. labrusca had relatively low totals. There were no significant correlations of the amounts of total resveratrols or any individual resveratrol between berry skins and leaves. All 75 cultivars can be divided into four groups based on the composition of resveratrols and their concentration by principal component analysis. Resveratrol content of grape berries and leaves varied largely with their genetic background and usage. Rootstock cultivars had a higher content of total resveratrols than the other germplasm. Total resveratrols were lower in leaves than berry skins in most cultivars. Cis-piceid was the most abundant resveratrol in most cultivars, and trans-res and trans-pd were

  12. Resveratrols in Grape Berry Skins and Leaves in Vitis Germplasm

    Science.gov (United States)

    Wang, Lijun; Xu, Man; Liu, Chunyan; Wang, Junfang; Xi, Huifen; Wu, Benhong; Loescher, Wayne; Duan, Wei; Fan, Peige; Li, Shaohua

    2013-01-01

    Background Resveratrol is an important stilbene that benefits human health. However, it is only distributed in a few species including grape and is very expensive. At present, grape has been an important source resveratrol. However, the details are scarce on resveratrol distribution in different Vitis species or cultivars. Methodology/Principal Finding The composition and content of resveratrols were investigated by HPLC for assessing genotypic variation in berry skins and leaves of 75 grape cultivars, belonging to 3 species and 7 interspecific hybrids. Trans-resveratrol, cis-piceid and trans-piceid were detected in berry skins and leaves, but cis-resveratrol was not. Resveratrol content largely varied with genetic background as well as usage. In most cultivars, total resveratrol including the above three compounds was higher in berry skins than leaves. In berry skins of most cultivars and leaves of almost all cultivars, cis-piceid was the most abundant resveratrol; trans-resveratrol and trans-piceid were minor components. Some specific cultivars were found with extremely high levels of trans-resveratrol, cis- piceid, trans-piceid or total resveratrols in berry skins or leaves. In skins and leaves, rootstock cultivars had a higher content of total resveratrols, and the cultivated European type cultivars and their hybrids with V. labrusca had relatively low totals. There were no significant correlations of the amounts of total resveratrols or any individual resveratrol between berry skins and leaves. All 75 cultivars can be divided into four groups based on the composition of resveratrols and their concentration by principal component analysis. Conclusion Resveratrol content of grape berries and leaves varied largely with their genetic background and usage. Rootstock cultivars had a higher content of total resveratrols than the other germplasm. Total resveratrols were lower in leaves than berry skins in most cultivars. Cis-piceid was the most abundant resveratrol in

  13. Suppression of Poxvirus Replication by Resveratrol

    Directory of Open Access Journals (Sweden)

    Shuai Cao

    2017-11-01

    Full Text Available Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV, the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  14. Development and in vitro assessment of psoralen and resveratrol co-loaded ultradeformable liposomes for the treatment of vitiligo.

    Science.gov (United States)

    Doppalapudi, Sindhu; Mahira, Shaheen; Khan, Wahid

    2017-09-01

    Vitiligo is a de-pigmenting skin disorder characterized by white patches on skin due to partial or complete loss of melanocytes. Psoralen in combination with ultraviolet-A (PUVA) acts by stimulation of melanin content and tyrosinase activity in melanocytes. Resveratrol, a sirtuin activator and a potential anti-oxidant reduce oxidative stress which is one of the triggering factors for initiation of vitiligo. Despite their therapeutic activity, weak percutaneous permeability of psoralen and poor solubility of resveratrol hinders their effective topical administration. The aim of present study is to formulate ultradeformable liposomes (UDL) co-loaded with psoralen and resveratrol for evaluation of PUVA and anti-oxidant combination in vitiligo treatment. For this purpose, UDL composed of DC-Chol, cholesterol and sodium deoxy cholate were prepared for their co-delivery. Liposomal carriers were characterized and evaluated for their efficacy using B16F10 cell line. Free radical scavenging potential was also determined for these carriers by in vitro anti-oxidant assays. Optimal co-loaded UDL with particle size ranging from 120 to 130nm, zeta potential of +46.2mV, entrapment efficiency of 74.09% (psoralen) and 76.91% (resveratrol) were obtained. Compared to control, co-loaded UDL showed significant stimulation of melanin and tyrosinase activity with major contribution of psoralen. Further, co-loaded UDL also exhibited potential free radical scavenging activity where resveratrol played a key role. Hence, psoralen and resveratrol co-loaded UDL acts in vitiligo through dual mechanisms of action viz., stimulation of melanin and tyrosinase activity as well as by anti-oxidant activity. These findings indicate that psoralen and resveratrol co-loaded UDL has the promising therapeutic potential for the treatment of vitiligo. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Resveratrol as a potential therapeutic drug for respiratory system diseases.

    Science.gov (United States)

    Zhu, Xiao-Dan; Lei, Xiao-Ping; Dong, Wen-Bin

    2017-01-01

    Respiratory system diseases are common and major ailments that seriously endanger human health. Resveratrol, a polyphenolic phytoalexin, is considered an anti-inflammatory, antioxidant, and anticancer agent. Thanks to its wide range of biological activities, resveratrol has become a hotspot in many fields, including respiratory system diseases. Indeed, research has demonstrated that resveratrol is helpful to relieve pulmonary function in the general population. Meanwhile, growing evidence indicates that resveratrol plays a protective role in respiratory system diseases. This review aimed to summarize the main protective effects of resveratrol in respiratory system diseases, including its anti-inflammatory, antiapoptotic, antioxidant, antifibrotic, antihypertensive, and anticancer activities. We found that resveratrol plays a protective role in the respiratory system through a variety of mechanisms, and so it may become a new drug for the treatment of respiratory system diseases.

  16. Study of radioprotective effect of the resveratrol

    International Nuclear Information System (INIS)

    Moreno, Carolina dos Santos

    2009-01-01

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Momesso, Roberta Grazzielli Ramos Alves Passarelli

    2010-07-01

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

  18. Effects of Resveratrol on Ovarian Morphology, Plasma Anti-Mullerian Hormone, IGF-1 Levels, and Oxidative Stress Parameters in a Rat Model of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Ergenoglu, Mete; Yildirim, Nuri; Yildirim, Alkim Gulsah Sahingoz; Yeniel, Ozgur; Erbas, Oytun; Yavasoglu, Altug; Taskiran, Dilek; Karadadas, Nedim

    2015-08-01

    To evaluate the effects of resveratrol in a rat model of polycystic ovarian syndrome (PCOS). After PCOS model was formed by subcutaneous dihydrotestosterone pellets, rats were randomly divided into 2 groups. The first group (n = 7) was treated with 1 mL/kg/d isotonic saline and the second group (n = 7) was treated with 10 mg/kg/d resveratrol. Seven rats were taken as controls without any medication. Our results showed (1) significant reduction in the number of antral follicle counts (P < .01); (2) significantly decreased plasma anti-Mullerian hormone and insulin-like growth factor 1 levels (P < .01 and P < .05, respectively); (3) significantly lower superoxide dismutase activity (P < .05); and (4) significantly increased glutathione peroxidase content (P < .01) following resveratrol treatment. Resveratrol appears to be effective in the treatment of PCOS due to its antioxidant properties. Future clinical studies with different dosages might provide useful implementations to our practice. © The Author(s) 2015.

  19. Antioxidants in food: content, measurement, significance, action, cautions, caveats, and research needs.

    Science.gov (United States)

    Benzie, Iris F F; Choi, Siu-Wai

    2014-01-01

    "total antioxidant content" of food will be presented. The FRAP assay and the modified version FRASC will be described, and the total antioxidant content (as the FRAP value) of a range of foods will be presented. Finally, issues of bioavailability and redox balance will be discussed in relation to the biological significance and molecular action of antioxidants in foods, some caution and caveats are presented about overcoming biological barriers to absorption of antioxidant phytochemicals, and research needs to further our understanding in the important area of food, antioxidants, and health will be highlighted. © 2014 Elsevier Inc. All rights reserved.

  20. VaCPK20 gene overexpression significantly increased resveratrol content and expression of stilbene synthase genes in cell cultures of Vitis amurensis Rupr.

    Science.gov (United States)

    Aleynova-Shumakova, O A; Dubrovina, A S; Manyakhin, A Y; Karetin, Y A; Kiselev, K V

    2014-06-01

    Resveratrol, a naturally occurring plant phenol, has been reported to exhibit a wide range of valuable biological and pharmacological properties. In the present investigation, we show that transformation of a Vitis amurensis Rupr. cell suspension with the gene VaCPK20 for a calcium-dependent protein kinase (CDPK) under the control of double CaMV 35S promoter increased resveratrol production in five independently transformed cell lines in 9-68 times compared with control cells. The VaCPK20-transformed calli were capable of producing 0.04-0.42 % dry wt. of resveratrol, while the control calli produced up to 0.008 % dry wt. of resveratrol Also, we characterized expression of stilbene synthase (STS) genes in the five VaCPK20-transgenic cell lines of V. amurensis. In all VaCPK20-transgenic cell lines, expression of VaSTS7 increased; while expression of VaSTS1 decreased. We suggest that transformation of V. amurensis calli with the VaCPK20 gene induced resveratrol accumulation via enhancement of expression of the VaSTS7 gene involved in resveratrol biosynthesis. The obtained data first demonstrate that overexpression of a CDPK gene resulted in increased accumulation of a stilbenoid phytoalexine in transgenic plant cells. We propose that the VaCPK20 gene could play an important role in the regulation of resveratrol biosynthesis in grape cells.

  1. Resveratrol for prenatal-stress-induced oxidative damage in growing brain and its consequences on survival of neurons.

    Science.gov (United States)

    Madhyastha, Sampath; Sahu, Sudhanshu Sekhar; Rao, Gayathri

    2014-02-01

    Prenatal-stress-induced neuronal damage in offspring is multifactorial, including oxidative damage in the developing brain. Resveratrol is known to exert its neuroprotective potentials by upregulating several antioxidant systems. Hence, the study was undertaken to evaluate the neuroprotective effect of resveratrol against prenatal-stress-induced hippocampal damage and oxidative damage in neonate rat brains. Pregnant rats were subjected to restraint stress during early or late gestational period. Another set of rats received resveratrol during the entire gestational period along with early or late gestational stress. The study parameters included several antioxidant studies directly from rat brain homogenate on the 40th postnatal day and hippocampal neuronal assay on the 21st postnatal day. Early as well as late gestational stress resulted in a significant increase in lipid peroxidation and advanced oxidation protein products and decrease in total antioxidant activity and nitric oxide levels in rat brain homogenate. The neurons of the dentate gyrus were severely affected in early and late gestational stress, and only the neurons of the CA3 region were adversely affected in late gestational stress. Administration of resveratrol reversed the prenatal-stress-induced oxidative damage and neurons of dentate gyrus but not the CA3 hippocampal neurons. These results show the neuroprotective abilities of resveratrol against prenatal-stress-induced oxidative damage in neonatal rat brain.

  2. Curcumin and resveratrol rescue cortical-hippocampal system from chronic fluoride-induced neurodegeneration and enhance memory retrieval.

    Science.gov (United States)

    Sharma, Chhavi; Suhalka, Pooja; Bhatnagar, Maheep

    2018-04-13

    The aim of this study was: (1) to evaluate the neuroprotective effect of resveratrol and curcumin on nicotinamide adenine dinucleotide phosphate diaphorase activity in neuronal cell in subregions of mice brain, (2) to evaluate the effects on antioxidant status and (3) to evaluate the protective effects of phytochemicals on learning and memory following fluoride exposure. Young mice (one month old, body weight (BW) 30 ± 5 mg) were provided with 120 ppm sodium fluoride dissolved in drinking water. They were given curcumin (30 mg/kg BW) or resveratrol (30 mg/kg BW) orally once in a day up to 30 days. Effects of resveratrol and curcumin on spatial learning and memory were studied using Morris water maze and classic maze test. Effects on brain antioxidants' (lactose dehydrogenase (LDH), malondialdehyde and reactive oxygen species) status were also studied in vitro. Histochemistry was done to assess the effect of treatments on nitric oxide neurotransmitter. Our study showed that in fluoride-treated animals, the number of nicotinamide adenine dinucleotide phosphate diaphorase positive neurons, intracellular Ca 2+ , reactive oxygen species level, LDH and malondialdehyde concentration increased significantly. Interestingly, after treatment with curcumin or resveratrol, a significant decrease in the number of nicotinamide adenine dinucleotide phosphate diaphorase positive neurons and antioxidant status was observed. This decrease was more considerable in resveratrol-treated group. Our study indicates that both antioxidants, curcumin and resveratrol, are useful in reducing neurodegeneration in selective areas of cornus ammonis 1 (CA1), CA3, dentate gyrus (DG) and the cortex of mice brain and in recuperating the loss of memory and learning caused due to fluoride exposure.

  3. Aggregation state and pKa values of (E)-resveratrol as determined by fluorescence spectroscopy and UV-visible absorption.

    Science.gov (United States)

    López-Nicolás, José Manuel; García-Carmona, Francisco

    2008-09-10

    Whether or not (E)-resveratrol can be used as a functional ingredient in foods depends on its structure at different concentrations and pH values. For this reason, the aggregation state of (E)-resveratrol at acidic and basic pH is investigated here for the first time. The data show that (E)-resveratrol forms aggregates above a certain critical concentration, and this concentration is lower at acid (12.5 microM at pH 5.5) than at basic pH values (37 microM at pH 10.5). Moreover, although several papers have focused on the effect of the protonation state of (E)-resveratrol on its biological activity, different data concerning the acidic dissociation constants of this natural antioxidant have been reported in the literature. The present paper shows a way of determining the acidic dissociation constants (pKa1 = 8.8, pKa2 = 9.8, pKa3 = 11.4) of (E)-resveratrol in aqueous medium using both absorbance and fluorescence spectroscopy. Furthermore, the spectroscopic study of (E)-resveratrol under different ionization states corresponding to the deprotonation of the hydroxyl groups present in the molecule shows significant differences among the absorbance, excitation, and emission spectra of (E)-resveratrol that have not previously been reported.

  4. Probing the position of resveratrol in lipid bilayers

    DEFF Research Database (Denmark)

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

    2015-01-01

    The effect of the natural antioxidant resveratrol on the structure of solid supported di-palmitoyl-phosphatidyl-choline (DPPC) bilayers in their fluid state was investigated by neutron reflectometry. Results reveal an accumulation of resveratrol (up to 25%, mol/mol) inside the headgroups...... and they exclude its presence in the hydrophobic core. The presence of resveratrol induces an increase of the average thickness and of the interfacial roughness of the headgroup layer. This may be due to a change of the tilt angle of the phosphocholine headgroups residing next to the resveratrol to a more upright...... orientation and leading to a reduction of the projected area per headgroup. This effect is propagated into the hydrophobic core, where the chain packing is modified despite the absence of resveratrol. When interacting with a DPPC/cholesterol membrane, resveratrol has a similar effect on the neighboring PC...

  5. Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design.

    Science.gov (United States)

    Hao, Jifu; Gao, Yun; Zhao, Jing; Zhang, Jimei; Li, Qiankui; Zhao, Zhongxi; Liu, Jiyong

    2015-02-01

    Resveratrol, a natural polyphenolic component, has inspired considerable interest for its extensive physiological activities. However, the poor solubility of resveratrol circumscribes its therapeutic applications. The purpose of this study was to optimize and prepare resveratrol nanosuspensions using the antisolvent precipitation method. The effects of crucial formulation and process variables (drug concentration, stabilizer, and surfactant contents) on particle size were investigated by utilizing a three-factor three-level Box-Behnken design (BBD) to perform this experiment. Different mathematical polynomial models were used to identify the impact of selected parameters and to evaluate their interrelationship for predictive formulation purposes. The optimal formulation consisted of drug 29.2 (mg/ml), polyvinylpyrrolidone (PVP) K17 0.38%, and F188 3.63%, respectively. The morphology of nanosuspensions was found to be near-spherical shaped by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis confirmed that the nanoparticles were in the amorphous state. Furthermore, in comparison to raw material, resveratrol nanosuspensions showed significantly enhanced saturation solubility and accelerated dissolution rate resulting from the decrease in particle size and the amorphous status of nanoparticles. Meanwhile, resveratrol nanosuspensions exhibited the similar antioxidant potency to that of raw resveratrol. The in vivo pharmacokinetic study revealed that the C max and AUC0→∞ values of nanosuspension were approximately 3.35- and 1.27-fold greater than those of reference preparation, respectively. Taken together, these results suggest that this study provides a beneficial approach to address the poor solubility issue of the resveratrol and affords a rational strategy to widen the application range of this interesting substance.

  6. Stability evaluation of resveratrol submitted to ionizing radiation

    International Nuclear Information System (INIS)

    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.

    2009-01-01

    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)

  7. 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)

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

    Science.gov (United States)

    Zhang, Xiaolin; Jiang, Anmin; Qi, Banghua; Ma, Zhongyou; Xiong, Youyi; Dou, Jinfeng; Wang, Jianfei

    2015-11-20

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Antiviral Activity of Resveratrol against Human and Animal Viruses.

    Science.gov (United States)

    Abba, Yusuf; Hassim, Hasliza; Hamzah, Hazilawati; Noordin, Mohamed Mustapha

    2015-01-01

    Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections both in vitro and in vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβ pathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.

  11. Resveratrol in lung cancer- a systematic review.

    Science.gov (United States)

    Feng, Yuan; Zhou, Jihing; Jiang, Ying

    2016-01-01

    Resveratrol, a phytochemical known for its anti- oxidative properties has been explored worldwide for anticancer potential. We performed this systematic review and meta-analysis in order to register the efficacy of resveratrol against lung carcinogenesis. We searched PubMed for preclinical studies reporting efficacy of resveratrol alone or in combination with drugs like curcumin, cisplatin etc. against lung carcinogenesis. The primary outcome of eligible studies included change in overall tumor incidence as well as tumor size. In all of the above studies involving either animal models or in vitro cancer cell experiments a statistically significant reduction in tumor incidence emerged as compared with the control groups, yielding a relative risk reduction of 0.64 (p=0.002). This meta- analysis confirmed the potential of resveratrol against lung carcinogenesis. It can be concluded that resveratrol holds a good potential for future use as a highly efficient therapeutic agent to deal with deadly lung carcinogenesis.

  12. Resveratrol as an anti-cancer agent: A review.

    Science.gov (United States)

    Rauf, Abdur; Imran, Muhammad; Butt, Masood Sadiq; Nadeem, Muhammad; Peters, Dennis G; Mubarak, Mohammad S

    2016-12-21

    Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemopreventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.

  13. Resveratrol in prostate diseases - a short review.

    Science.gov (United States)

    Jasiński, Milosz; Jasińska, Lidia; Ogrodowczyk, Marcin

    2013-01-01

    Resveratrol is a plant-derived polyphenol suggested to have many beneficial health effects, including antioxidant, anti-inflammatory, anti-proliferative, proapoptotic, and anti-angiogenic. It is even specu- lated that uptake of resveratrol by red wine consumption could be behind the so-called French paradox the lower incidence of cardiovascular diseases in the French population. These properties, together with good absorption and tolerance, would make it an attractive agent in prostatic diseases, especially in cancer prevention and treatment. MEDLINE search (keywords "prostate res- veratrol") resulted in 39 research papers published since 2007. It has been shown that resveratol down-regulate androgen receptor expression, inhibit proliferation, and promote apop- tosis in prostate cancer cell lines and enhance their sensitivity to ionizing radiation. Several studies on animal prostate cancer development also suggest that resveratrol is able do delay or prevent carcino- genesis in prostate. Despite these promising results, there is no proof of any therapeutic properties of resveratrol in prostate diseases from human clinical trials nor any information about ongoing trials in this field. Resveratrol is produced and sold as a nutritional supplement, there is not enough clinical evidence to justify a recommendation for the administration of resveratrol in humans at present.

  14. Resveratrol: A Potential Hippocampal Plasticity Enhancer.

    Science.gov (United States)

    Dias, Gisele Pereira; Cocks, Graham; do Nascimento Bevilaqua, Mário Cesar; Nardi, Antonio Egidio; Thuret, Sandrine

    2016-01-01

    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.

  15. Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

    Science.gov (United States)

    Guerra, Maria Cristina; Leite, Marina Concli; Souza, Diogo Onofre; Gonçalves, Carlos-Alberto; Gottfried, Carmem

    2012-01-01

    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. PMID:23284918

  16. Resveratrol prevents ammonia toxicity in astroglial cells.

    Directory of Open Access Journals (Sweden)

    Larissa Daniele Bobermin

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

  17. Anti-inflammatory responses of resveratrol.

    Science.gov (United States)

    Das, Samarjit; Das, Dipak K

    2007-09-01

    Resveratrol (trans-3,4',5-trihydroxystilbene), a natural polyphenolic, non-flavonoid antioxidant, is a phytoalexin found in many plants including grapes, nuts and berries. Recent studies have documented that resveratrol has various health benefits, such as cardiovascular and cancer preventive properties. However, the experimental basis for such health benefit is not fully understood. One of the possible mechanisms for its protective activities is by down regulation of the inflammatory responses. That includes the inhibition of synthesis and release of pro-inflammatory mediators, modifications of eicosanoid synthesis, inhibition of some activated immune cells, or inhibiting the enzymes, such as cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2), which are responsible for the synthesis of pro-inflammatory mediators through the inhibitory effect of resveratrol on transcription factors like nuclear factor kappaB (NFkappaB) or activator protein-1 (AP-1). Being a phenolic compound, resveratrol certainly possesses a low bioavailability and most importantly, a rapid clearance from the plasma. Recent growing interest in varying protective nature of resveratrol may clinically also hold a respectable position as a better alternative for anti-inflammatory drugs. The purpose of this review is to provide evidence that resveratrol exhibits potent anti-inflammatory activity and also to explain the underling mechanism for both resveratrol- induced cardioprotective and anti-inflammatory properties. While it is true that the cardioprotective properties of resveratrol are likely attributable, at least in part, to its anti-inflammatory properties, the mechanisms discussed address foremost mechanisms for the anti-inflammatory activity which, in turn, is responsible for cardioprotection.

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

    Directory of Open Access Journals (Sweden)

    Yuanli Liu

    Full Text Available 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.

  19. A comparative assessment of antiproliferative properties of resveratrol and ethanol leaf extract of Anogeissus leiocarpus (DC) Guill and Perr against HepG2 hepatocarcinoma cells.

    Science.gov (United States)

    Olugbami, Jeremiah Olorunjuwon; Damoiseaux, Robert; France, Bryan; Onibiyo, Esther Modupe; Gbadegesin, Michael Adedapo; Sharma, Shivani; Gimzewski, James Kazimierz; Odunola, Oyeronke Adunni

    2017-08-02

    Epidemiological and experimental evidences have shown cancer as a leading cause of death worldwide. Although the folklore use of plants as a reliable source of health-restoring principles is well-documented, the search for more of such plants that are active against diseases, such as cancer, continues. We report here a laboratory-based evidence of the relevance of an ethanol leaf extract of Anogeissus leiocarpus (A2L) in comparison with resveratrol, a natural polyphenol, in cancer therapy. The quantitative assessment of flavonoid and phenolic contents involved quercetin and gallic acid as standards, respectively were determined using spectrophotometry. Cytotoxicity was determined fluorometrically using propidium-iodide-staining method. Antioxidant status, adenosine triphosphate (ATP) levels, caspase activities and mitochondrial integrity were assessed using fluorometry/luminometry. The antioxidant assay demonstrated that A2L possesses a strong antioxidant capacity as compared with the reference compounds, ascorbic acid and butylated hydroxytoluene. This is further buttressed by the significantly high level of phenolics obtained in the quantitative assessment of the extract. A 72-h post-treatment examination indicated that both A2L and resveratrol modulate the proliferation of HepG2 liver carcinoma cells in a time- and concentration-dependent manner. Determination of the total nuclei area, propidium-iodide negative and positive nuclei areas all further buttress the modulation of cell proliferation by A2L and resveratrol with the indication that the observed cell death is due to apoptosis and necrosis at lower and higher concentrations of treatments respectively. At lower concentrations (0.39-3.13 μg/mL), resveratrol possesses higher tendencies to activate caspases 3 and 7. Bioenergetically, both resveratrol and A2L do not adversely affect the cells at lower concentrations (0.39-6.25 μg/mL for resveratrol and 12.5-100.0 μg/mL for A2L) except at higher

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

    Science.gov (United States)

    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 Measurements: Blood samples taken 48 hours before and 18–32 hours after the marathon were analysed for white blood cell count (WBC) and C-reactive protein (CRP). A VAS score was taken at the same times as the blood samples to assess delayed onset muscle soreness. Results: There were no significant differences between the two groups in terms of changes occurring between pre- and post- tests for WBC, CRP or VAS. Conclusions: There were no differences in immune response or delayed onset muscle soreness between resveratrol and placebo after a marathon. Further investigations are needed with longer treatment time and higher doses, analysing additional parameters such interleukins for a possible effect of resveratrol on the inflammatory response due to extensive exercise. To avoid a type II error, 17 subjects in each group would be required. PMID:25147765

  1. Neuroprotection by resveratrol in diabetic neuropathy: concepts & mechanisms.

    Science.gov (United States)

    Kumar, A; Negi, G; Sharma, S S

    2013-01-01

    Resveratrol is a naturally occurring phytoalexin found in many plants, nuts and fruits and is abundant in grapes and red wine. Resveratrol possesses a wide range of biological activities which include antioxidant, anti-inflammatory, chemoprotective, chemopreventive etc. Resveratrol has been investigated extensively in diabetes and its complications which suggest its anti-diabetic activity and protective effect against various diabetic complications. Neurons are extremely susceptible to oxidant-induced damage which may be due to their high rate of oxygen consumption and low levels of antioxidant defence enzymes. Traditionally, it was thought that the protective actions of resveratrol in diabetic neuropathy are due to its intrinsic radical scavenger properties. However, recently many other associated or separate mechanisms like upregulation of Nrf2, SIRT1 and inhibition of NF-κB, AP-1 have been proposed for its beneficial effect against nerve dysfunction. This present review discusses the neuroprotective effects of resveratrol that have been observed in experimental diabetic neuropathy and possible mechanistic explanations, as these effects may provide directions for the development of newer therapies. Futuristic therapies can be based on either resveratrol or its analogs with better bioavailability, or combining the resveratrol with existing therapies.

  2. 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. © 2015 New York Academy of Sciences.

  3. The therapeutic potential of resveratrol: a review of clinical trials.

    Science.gov (United States)

    Berman, Adi Y; Motechin, Rachel A; Wiesenfeld, Maia Y; Holz, Marina K

    2017-01-01

    Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. We found that for neurological disorders, cardiovascular diseases, and diabetes, the current clinical trials show that resveratrol was well tolerated and beneficially influenced disease biomarkers. However resveratrol had ambiguous and sometimes even detrimental effects in certain types of cancers and in NAFLD. In most of the clinical trials, the major obstacle presented was resveratrol's poor bioavailability. Thus, this work provides useful considerations for the planning and design of future pre-clinical and clinical research on resveratrol.

  4. Resveratrol Role in Autoimmune Disease—A Mini-Review

    Directory of Open Access Journals (Sweden)

    Ana Lígia de Brito Oliveira

    2017-12-01

    Full Text Available Autoimmune diseases are still considered to be pressing concerns due the fact that they are leaders in death and disability causes worldwide. Resveratrol is a polyphenol derived from a variety of foods and beverages, including red grapes and red wine. Anti-inflammatory, antioxidant, and antiaging properties of resveratrol have been reported, and in some animal and human studies this compound reduced and ameliorated the progression of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and type 1 diabetes mellitus. Thus, this review aims to summarize and critically analyze the role of resveratrol in the modulation of several organ-specific or systemic autoimmune diseases.

  5. Multiplicity of effects and health benefits of resveratrol

    Directory of Open Access Journals (Sweden)

    Lolita Kuršvietienė

    2016-01-01

    Full Text Available Resveratrol is mainly found in grapes and red wine, also in some plants and fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries. Moreover, nowadays this compound is available as purified preparation and dietary supplement. Resveratrol provides a wide range of benefits, including cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood glucose-lowering and anticancer activities, hence it exhibits a complex mode of action. During the recent years, these properties have been widely studied in animal and human models, both in vitro and in vivo. This paper is intended to present information published during the recent years on the biological activities and multiple effects of resveratrol.

  6. Resveratrol Role in Autoimmune Disease-A Mini-Review.

    Science.gov (United States)

    Oliveira, Ana Lígia de Brito; Monteiro, Valter Vinicius Silva; Navegantes-Lima, Kely Campos; Reis, Jordano Ferreira; Gomes, Rafaelli de Souza; Rodrigues, Dávila Valentina Silva; Gaspar, Silvia Letícia de França; Monteiro, Marta Chagas

    2017-12-01

    Autoimmune diseases are still considered to be pressing concerns due the fact that they are leaders in death and disability causes worldwide. Resveratrol is a polyphenol derived from a variety of foods and beverages, including red grapes and red wine. Anti-inflammatory, antioxidant, and antiaging properties of resveratrol have been reported, and in some animal and human studies this compound reduced and ameliorated the progression of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and type 1 diabetes mellitus. Thus, this review aims to summarize and critically analyze the role of resveratrol in the modulation of several organ-specific or systemic autoimmune diseases.

  7. Resveratrol as a potential therapeutic drug for respiratory system diseases

    OpenAIRE

    Zhu, Xiao-dan; Lei, Xiao-ping; Dong, Wen-bin

    2017-01-01

    Xiao-dan Zhu, Xiao-ping Lei, Wen-bin Dong Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China Abstract: Respiratory system diseases are common and major ailments that seriously endanger human health. Resveratrol, a polyphenolic phytoalexin, is considered an anti-inflammatory, antioxidant, and anticancer agent. Thanks to its wide range of biological activities, resveratrol has become a hotspot in many ...

  8. Resveratrol Prevents Monocrotaline-induced Pulmonary Hypertension in Rats

    OpenAIRE

    Csiszar, Anna; Labinskyy, Nazar; Olson, Susan; Pinto, John T.; Gupte, Sachin; Wu, Joseph M.; Hu, Furong; Ballabh, Praveen; Podlutsky, Andrej; Losonczy, Gyorgy; de Cabo, Rafael; Mathew, Rajamma; Wolin, Michael S.; Ungvari, Zoltan

    2009-01-01

    Proliferation of pulmonary arterial smooth muscle cells, endothelial-dysfunction, oxidative stress and inflammation promote the development of pulmonary hypertension. Resveratrol is a polyphenolic compound that exerts anti-oxidant and anti-inflammatory protective effects in the systemic circulation, but its effects on pulmonary arteries remain poorly defined. The present study was undertaken to investigate the efficacy of resveratrol to prevent pulmonary hypertension. Rats injected with monoc...

  9. Protective effects of Resveratrol against chemotherapy drug Cisplatin induced hepatotoxicity in the rat

    Directory of Open Access Journals (Sweden)

    ramin kaffashielahi

    2014-02-01

    Full Text Available Drug therapy of cancer which is carried out by natural, synthetic or biological substances is associated with complications. Cisplatin as an anticancer drug, is hepatotoxic at high doses. Oxidative stress has been proven to be involved in cisplatin-induced toxicity. Because of antioxidant potential of resveratrol, this study was conducted to assess the protective effects of resveratrol, on cisplatin-induced hepatotoxicity in the rat. Forty male Wistar rats were randomly divided into four equal groups. Group 1 was used as control. For induction of hepatic injury in groups 2-4, cisplatin (3 mg/kg was injected once every five days intraperitoneally. Groups 3 and 4 received silymarin (100 mg/kg and resveratrol (20 mg/kg respectively, daily for 4 weeks via intraperitoneal route. At the end of experiment, serum levels of aspartate and alanine transaminases, lactate dehydogenase and total bilirubin, albumin and total proteins were assessed. Malondialdehyde, reduced glutathione and activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were assayed in liver homogenates. Finally, the biochemical findings were matched with histopathological verification. In group 4, resveratrol significantly (p

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

    Directory of Open Access Journals (Sweden)

    Rebecca K. Vella

    2015-01-01

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

  11. Resveratrol and Health

    DEFF Research Database (Denmark)

    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...... of red wine. Resveratrol has also been produced by chemical synthesis or by biotechnological synthesis and is sold as a nutritional supplement derived primarily from Japanese knotweed....

  12. Significance of Serum Total Oxidant/Antioxidant Status in Patients with Colorectal Cancer.

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    Rong Wu

    Full Text Available Oxidative stress is involved in a variety of diseases. Prospective studies investigating the relationship between oxidative stress biomarkers and the status and development of colorectal cancer (CRC are scarce; previous studies have failed to establish a relationship between the serum total oxidant/antioxidant status and CRC. Therefore, we compared the total serum oxidant/antioxidant levels of CRC patients and healthy subjects, and analyzed their clinical significance in the CRC. Fasting blood samples from 132 CRC patients and 64 healthy subjects were collected. Oxidative stress parameters, including total oxidant status (TOS and total antioxidant status (TAS, were measured, and the oxidative stress index (OSI was calculated. The TOS and OSI levels increased significantly (P0.05.However, the levels of TOS, TAS, and OSI were significantly different between patients with no metastasis and those with metastases to two organs (P<0.05 Finally, the parameters are affected by smoking and drinking, and subsequent research should be conducted excluding the relevant influencing factors.

  13. Resveratrol as a growth substrate for bacteria from the rhizosphere.

    Science.gov (United States)

    Kurt, Zohre; Minoia, Marco; Spain, Jim C

    2018-03-09

    Resveratrol is among the best-known secondary plant metabolites because of its antioxidant, anti-inflammatory and anticancer properties. It also is an important allelopathic chemical widely credited with protection of plants from pathogens. The ecological role of resveratrol in natural habitats is difficult to establish rigorously because it does not seem to accumulate outside of plant tissue. It is likely that bacterial degradation plays a key role in determining the persistence, and thus the ecological role, of resveratrol in soil. Here we report the isolation of an Acinetobacter species that can use resveratrol as a sole carbon source from the rhizosphere of peanut plants. Both molecular and biochemical techniques indicate that the pathway starts with the conversion of resveratrol to 3,5-dihydroxybenzaldehyde and 4-hydroxybenzaldehyde. The aldehydes are oxidized to substituted benzoates that subsequently enter central metabolism. The gene that encodes the enzyme responsible for the oxidative cleavage of resveratrol was cloned, and expressed in E. coli to establish its function. Its physiological role in the resveratrol catabolic pathway was established by knockouts and by RT-qPCR demonstration of expression during growth on resveratrol. The results establish the presence and capabilities of resveratrol degrading bacteria in the rhizosphere of the peanut plants and set the stage for studies to evaluate the role of the bacteria in plant allelopathy. IMPORTANCE In addition to its antioxidant properties, resveratrol is an example of a broad array of allelopathic chemicals produced by plants to inhibit competitors, herbivores and pathogens. Bacterial degradation of such chemicals in the rhizosphere would reduce the effects of the chemicals. Therefore, it is important to understand the activity and ecological role of bacteria that biodegrade resveratrol near the plants that produce it. This study describes the isolation from the peanut rhizosphere of bacteria that can

  14. 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

  15. Original article. Protective effect of resveratrol against neuronal damage through oxidative stress in cerebral hemisphere of aluminum and fluoride treated rats

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    Nalagoni Chandra Shakar Reddy

    2016-06-01

    Full Text Available Aluminum has no defined biological function and it is potentially involved in the pathogenesis of neurodegenerative disorders. Furthermore, the presence of fluoride causes more aluminum to accumulate in the brain, resulting in increased neuronal damage. In recent years, resveratrol through its ameliorative effects was found to be a neuroprotectant. This study reports the protective effects of resveratrol on combined aluminum and fluoride induced neuronal damage through oxidative stress in rats. Protective effects of resveratrol (30 mg/kg b.w on markers of oxidative stress were determined in rats exposed to aluminum chloride (100 mg/kg b.w along with sodium fluoride (10 mg/kg b.w for 8 weeks. The results showed a statistically significant (p<0.05 increase in lipid peroxidation (LPx as well as a significant (p<0.05 decrease in superoxide dismutase and catalase activity. Enlarged cells, neurofibrillary tangles, and vacuolar spaces showing oxidative stress in the cerebral cortex were also observed in hematoxylin and eosin stained sections in aluminum and fluoride treated rats. Administration of resveratrol along with aluminum + fluoride showed significant reversal of oxidative stress and neuronal damage in rats. Thus resveratrol potentially acts as a neuroprotectant against aluminum chloride + sodium fluoride induced neuronal damage through its anti-oxidant efficacy.

  16. Effect of different presentations of resveratrol on cell proliferation and epitelial thickness of the oral mucosa of wistar rats

    Directory of Open Access Journals (Sweden)

    Luciano Henrique Jesus

    2017-09-01

    Full Text Available Introduction: Grape is one of the most important fruit crops across the world and can be consumed in different ways. There has been a growing interest in the role of antioxidants such as resveratrol, which can be found in grape skin, in oral and dental tissues. Thus, the objective of this study was to analyze the effect of different presentations of resveratrol on cell proliferation and epithelial thickness of the oral mucosa of Wistar rats. Methods: Fifty male Wistar rats were randomly divided into five groups: water/control, red wine, grape juice, 12% alcoholic solution/ethanol and aqueous solution of resveratrol. Samples of palatal and tongue mucosa were collected for a histomorphometric analysis using hematoxylin-eosin staining and the argyrophilic nucleolar organizer region (AgNOR technique for quantification of cell proliferation. Results: As to epithelial thickness, both the tongue and the palate showed a statistically significant difference between the control group and the other groups, with greater decrease in the resveratrol and the wine groups. In the suprabasal layer of both the tongue and the palate epithelium, red wine reduced the rate of cell proliferation, while ethanol increased it. In the basal layer of the tongue epithelium, there was a statistically significant difference between the control, the grape juice and the resveratrol groups and the ethanol group, with increased cell proliferation in the ethanol group. Conclusions: Wine does not interfere in the physiological renewal of the basal layer of the buccal epithelium and exerts a protective action by reducing the cell proliferation rate of the suprabasal layer. Keywords: Resveratrol; grape juice; wine; cell proliferation; epithelial thickness

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

    Directory of Open Access Journals (Sweden)

    Zoe eFonseca-Kelly

    2012-05-01

    Full Text Available 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 studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for multiple sclerosis.

  18. 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.

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

    International Nuclear Information System (INIS)

    Moreno, Carolina S.; Santos, Dymes R.A.; Vieira, Daniel P.; Rogero, Sizue O.; Rogero, Jose R.; Sakuraba, Roberto K.; Weltman, Eduardo; Cruz, Aurea S.; Santos, Rezolina P.

    2015-01-01

    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)

  20. 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)

  1. 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

    2016-04-05

    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.

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

    NARCIS (Netherlands)

    Friedrich, R.B.; Kann, B.; Coradini, K.; Offerhaus, Herman 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

  3. The Effects of Resveratrol on Hyperoxia-induced Lung Injury in Neonatal Rats

    Directory of Open Access Journals (Sweden)

    Özmert M.A. Özdemir

    2014-10-01

    Conclusion: This experimental study showed that oxidative stress and NO contributed to the pathogenesis of hyperoxia-induced lung injury, and that resveratrol had a preventive effect on hyperoxic lung injury through its anti-inflammatory and antioxidant properties.

  4. Dual Mechanism of Action of Resveratrol in Notch Signaling ...

    African Journals Online (AJOL)

    Results: The results revealed that resveratrol treatment exhibited dual mechanisms of action on the activation of Notch signaling in osteosarcoma cells. The osteosarcoma cell lines, MG-63 and U2OS, when exposed to 20 μM concentration of resveratrol for 48 h showed significant toxicity compared to untreated cells.

  5. Resveratrol, a dietary polyphenolic phytoalexin, is a functional scavenger of peroxynitrite

    Science.gov (United States)

    Holthoff, Joseph H.; Woodling, Kellie A.; Doerge, Daniel R.; Burns, Samuel T.; Hinson, Jack A.; Mayeux, Philip R.

    2010-01-01

    Oxidant damage from reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major contributor to the cellular damage seen in numerous types of renal injury. Resveratrol (trans-3, 4′, 5-trihydroxystilbene) is a phytoalexin found naturally in many common food sources. The antioxidant properties of resveratrol are of particular interest because of the fundamental role that oxidant damage plays in numerous forms of kidney injury. To examine whether resveratrol could block damage to the renal epithelial cell line, mIMCD-3, cells were exposed to the peroxynitrite donor 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride (SIN-1). Resveratrol produced a concentration-dependent inhibition of cytotoxicity induced by SIN-1. To examine the mechanism of protection, resveratrol was incubated with authentic peroxynitrite and found to block nitration of bovine serum albumin with an EC50 value of 22.7 μM, in contrast to the known RNS scavenger, N-acetylcysteine, which inhibited nitration with an EC50 value of 439 μM. These data suggested that resveratrol could provide functional protection by directly scavenging peroxynitrite. To examine whether resveratrol was a substrate for peroxynitrite oxidation, resveratrol was reacted with authentic peroxynitrite. Resveratrol nitration products and dimers were detected using liquid chromatograph with tandem electrospray mass spectrometry. Similar products were detected in the media of cells treated with SIN-1 and resveratrol. Taken collectively, the data suggest that resveratrol is able to provide functional protection of renal tubular cells, at least in part, by directly scavenging the RNS peroxynitrite. This property of resveratrol may contribute to the understanding of its antioxidant activities. PMID:20599800

  6. Effect of apigenin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) in RAW-264.7 macrophages.

    Science.gov (United States)

    Palacz-Wrobel, Marta; Borkowska, Paulina; Paul-Samojedny, Monika; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Suchanek-Raif, Renata; Kowalski, Jan

    2017-09-01

    Polyphenols such as apigenin, kaempferol or resveratrol are typically found in plants, including fruits, vegetables, herbs and spices, which have a wide range of biological functions such as antioxidative, anti-inflammatory, vasodilative, anticoagulative and proapoptotic. Discovering such multifunctional compounds in widely consumed plant-based products - ones that both inhibit the release of TNF-α from tissue macrophages and at the same time enhance the secretion of IL-10 - would be an important signpost in the quest for effective pharmacological treatment of numerous diseases that have an inflammatory etiology. The aim of the study is to investigate the impact of biologically active polyphenols such as apigenin, resveratrol and kaempferol on gene expression and protein secretion of IL-10 and TNF-α in line RAW-264.7. Cells were cultured under standard conditions. IL-10 and TNF-α genes expression were examined using QRT-PCR and to assess cytokines concentration ELISA have been used. Apigenin, kaempferol and resveratrol at a dose 30μM significantly decrease the TNF-α expression and secretion. Apigenin decrease the IL-10 expression and secretion. Furthermore, increase in IL-10 secretion after administration of kaempferol and resveratrol were observed. In the process of administration of tested compounds before LPS, which activate macrophages, decrease of TNF-α secretion after apigenin and kaempferol and increase of IL-10 secretion after resveratrol were observed. The results of present work indicate that 1) apigenin, resveratrol and kaempferol may reduce the intensity of inflammatory processes by inhibiting the secretion of proinflammatory cytokine TNF-α, and resveratrol and kaempferol additionally by increasing the secretion of anti-inflammatory cytokine IL-10 2) the studies indicate the potentially beneficial - anti-inflammatory - impact of diet rich in products including apigenin, resveratrol and kaempferol. Copyright © 2017 Elsevier Masson SAS. All rights

  7. Nuts, especially walnuts, have both antioxidant quantity and efficacy and exhibit significant potential health benefits.

    Science.gov (United States)

    Vinson, Joe A; Cai, Yuxing

    2012-02-01

    Free and total (after basic hydrolysis) polyphenols in nine types of raw and roasted nuts and two types of peanut butter (54 commercial samples) were analyzed after methanol extraction by a single step Folin-Ciocalteu reagent using catechin as standard. Walnuts had the highest free and total polyphenols in both the combined raw and roasted samples. Total polyphenols in the nuts were significantly higher than free polyphenols. Roasting had little effect on either free or total polyphenols in nuts. Raw and roasted walnuts had the highest total polyphenols. The efficacy of raw and roasted nut antioxidants was assessed by measuring the ability of the free polyphenol nut extracts to inhibit the oxidation of lower density lipoproteins (LDL + VLDL). A nut polyphenol, catechin, was measured after binding of three nut extracts to lower density lipoproteins. Walnut polyphenols had the best efficacy among the nuts and also the highest lipoprotein-bound antioxidant activity. Based on USDA availability data, the per capita total polyphenols was 162 mg from nuts per day in 2008. This corresponds to 19% of the total polyphenols from fruits and vegetables, nuts, grains, oils and spices in the US diet. Nuts provided 158 mg of polyphenols per day to the European Union diet. Nuts are high in polyphenol antioxidants which by binding to lipoproteins would inhibit oxidative processes that lead to atherosclerosis in vivo. In human supplementation studies nuts have been shown to improve the lipid profile, increase endothelial function and reduce inflammation, all without causing weight gain. These qualities make nuts a nutritious healthy snack and food additive.

  8. Antioxidants

    Science.gov (United States)

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

  9. Significance of antioxidant potential of plants and its relevance to therapeutic applications.

    Science.gov (United States)

    Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong

    2015-01-01

    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

  10. Neuroprotective Properties and Mechanisms of Resveratrol in in Vitro and in Vivo Experimental Cerebral Stroke Models

    Science.gov (United States)

    2013-01-01

    Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and seeds and red wine, is known for its purported antioxidant activity in the vascular and nervous systems. In contrast to its direct antioxidant role within the central nervous system, recent research supports a protective mechanism through increasing endogenous cellular antioxidant defenses, which triggers a cascade of parallel neuroprotective pathways. A growing body of in vitro and in vivo evidence indicates that resveratrol acts through multiple pathways and reduces ischemic damage in vital organs, such as the heart and the brain, in various rodent models. Most of the protective biological actions of resveratrol have been associated with its antioxidative, anti-inflammatory, and antiapoptotic properties and other indirect pathways. Continued public interest and increasing resveratrol supplements on the market warrant a review of the available in vitro and in vivo science reported in the stroke-related literature. Rigorous clinical trials evaluating the effects of resveratrol in stroke are absent, though the general population consumption appears to be relatively safe. Resveratrol has shown potential for treating stroke in laboratory animals and in vitro human cell studies, yet there is still a need for human research in preclinical settings. This review summarizes many of the findings on the neuroprotective potential of resveratrol in cerebral stroke, focusing on both the in vitro and in vivo experimental models and some proposed mechanisms of action. PMID:23758534

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

    Science.gov (United States)

    Singh, Nilendra; Agrawal, Megha; Doré, Sylvain

    2013-08-21

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

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

    Directory of Open Access Journals (Sweden)

    Rossane Serafim Matos

    2012-02-01

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

  13. Antiviral Activity of Resveratrol against Human and Animal Viruses

    Directory of Open Access Journals (Sweden)

    Yusuf Abba

    2015-01-01

    Full Text Available Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections both in vitro and in vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβ pathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.

  14. Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage.

    Directory of Open Access Journals (Sweden)

    Vengatesh Ganapathy

    Full Text Available Electronic cigarette (EC aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs.The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells.Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS and total antioxidant capacity (TAC were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively.EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1, an enzyme essential for the removal of oxidative DNA damage.Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.

  15. Cosmetic Potential of a Liotropic Liquid Crystal Emulsion Containing Resveratrol

    Directory of Open Access Journals (Sweden)

    Laura Bonato Alves Oliveira

    2017-12-01

    Full Text Available Resveratrol is a natural substance that has been the target of many researchers over the years since it presents a variety of potential applications in the areas of cosmetics and medicine as a treatment for some diseases. Due to its high antioxidant capacity but low bioavailability, we evaluated the antiaging potential of resveratrol as a liotropic liquid crystal emulsion. Initially, we performed in vitro assays to quantify both the organoleptic characteristics and stability of the emulsion. Next, an in vivo trial was performed on the faces of 30 volunteers to determine the cream’s cosmetic potential and to measure porphyrins, skin barrier function, skin pigmentation, expression lines, and porosity. The emulsion maintained its characteristics during the in vitro assays and, in the in vivo trial, it had some effect only on pore size in forehead, without any significant effects on the other parameters. We had 6 dropouts throughout the study, then the final number of volunteers was 24. Most volunteers did not show any changes in skin pigmentation throughout the study. Similarly, there was not any noticeable improvement on any other parameters evaluated. However, volunteers related a high level of satisfaction with the product.

  16. Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Dong Suk; Choi, Yoorim; Choi, Seong Mi [Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul (Korea, Republic of); Park, Kwang Hwan [Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Jin Woo, E-mail: ljwos@yuhs.ac [Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul (Korea, Republic of)

    2015-11-27

    Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. In contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.

  17. 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

  18. Bioactive polyphenols from grapes and wine emphasized with resveratrol.

    Science.gov (United States)

    Latruffe, Norbert; Rifler, Jean-Pierre

    2013-01-01

    Grape polyphenols are abundant. They play essential roles in the plant's life, particularly in defence mechanisms. Moreover, the grape, fresh or dried, is a widely consumed fruit by humans, as are its by-products, grape juice and wine. They also contain vast and highly varied quantities of polyphenols. Like other phytophenols, grape and wine resveratrol is considered a protective micronutrient. Resveratrol is a well known antioxidant, for example, a protector of low-density lipoproteins against oxidation. Its applications are therefore highly varied. Research supports the idea that wine consumed regularly, without excess, is a natural biological product possesses preventive properties, and not only well-known properties against vascular diseases (illustrated by the so-called French paradox). At least in experimental models so far, resveratrol prevents infections, inflammation, neurodegenerative diseases, and cancer. This review addresses whether the pro-longevity properties of resveratrol are preserved in the human species. If such is the case, it will be possible to imagine new ways of eating based on natural foods, with or without supplements, based on resveratrol. On the other hand, studies such as ours are investigating the synergies between resveratrol and some of the many polyphenols found in wine. These studies should fill in the gaps between the study of a molecule tested in isolation or in a binary system (e.g., with alcohol) and this same molecule in its biological context.

  19. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced ...

    African Journals Online (AJOL)

    olayemitoyin

    In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrations and might be beneficial in ... Regular consumption of food rich in antioxidant are associated with numerous health ... inhibition of platelet aggregation (Wang et al., 2002), promotion of vasodilatation by ...

  20. 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

  1. Resveratrol fails to improve marginal mass engraftment of transplanted islets of Langerhans in mice.

    Science.gov (United States)

    McCall, Michael D; Pawlick, Rena; Shapiro, A M James

    2011-01-01

    One limitation of current islet transplantation protocols is the loss of up to 70% of the transplanted islet mass. Inflammatory events play a major role in islet loss including the cytokines TNFα and IL-1. Resveratrol, a compound with anti-inflammatory and anti-oxidant properties, has the potential to mitigate islet loss. Using a syngeneic marginal  after mouse islet transplantation model we tested the ability of resveratrol to enhance islet engraftment. We failed to show a difference in diabetes reversal between mice treated with vehicle and those treated with either 10 mg/kg (47.1% for resveratrol vs. 35.3% for control) or 50 mg/kg (20% for resveratrol vs. 22.2% for control) of resveratrol daily for three weeks. In addition, at one month there was no difference in glucose tolerance or graft survival (10 mg/kg: 552.6 ng/ml resveratrol group vs. 576.6 ng/ml control group; 50 mg/kg: 463 ng/ml resveratrol group vs. 444.1 ng/ml control group). In summary, over a wide range of doses, resveratrol did not exert a benefit on mouse islet engraftment. Further studies should be conducted with human islets before deeming resveratrol ineffective in islet engraftment and survival.

  2. 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...

  3. 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.

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

    Science.gov (United States)

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

    2016-05-01

    The addition of resveratrol, a polyphenol found in red wine and peanuts, to food products would help to provide the health benefits associated with the compound to the consumer in a wide array of food matrices. The bitterness of resveratrol and instability of its bioactive form in light are 2 major challenges with the incorporation of the compound into food products. Microencapsulation in a sodium caseinate matrix was utilized as a strategy to overcome these challenges. The objective of this research was to show the application of the resveratrol microcapsules in easy-to-consume foods. Consumer acceptance was evaluated for gummies and bars with encapsulated resveratrol in comparison to the controls. Four different controls were used: 1) without any resveratrol OR protein (Plain), 2) unencapsulated resveratrol (Resv), 3) sodium caseinate and unencapsulated resveratrol just mixed without encapsulation (P + R), and 4) sodium caseinate only (PRO). Two concentrations of resveratrol that have been shown to offer therapeutic effects in humans were tested (10 and 40 mg/d). The overall liking, evaluated using a 9-point scale, of bars with 10 mg of encapsulated resveratrol did not differ significantly from the control without any added resveratrol and protein (Plain) or from the controls with equivalent protein and/or resveratrol concentrations. For gummies, the samples with the resveratrol microcapsules had a significantly lower overall liking than the controls with the same protein and/or resveratrol content. This research demonstrated application of resveratrol microcapsules into easy-to-consume food products in order to deliver the health benefits to the consumer. © 2016 Institute of Food Technologists®

  5. Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Elgebaly, Ahmed; Radwan, Ibrahim A I; AboElnas, Mohamed M; Ibrahim, Hamza H; Eltoomy, Moutaz F M; Atta, Ahmed A; Mesalam, Hend A; Sayed, Alaa A; Othman, Amr A

    2017-03-01

    Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted. Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous. Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.

  6. 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...

  7. The antimicrobial action of resveratrol against Listeria monocytogenes in food-based models and its antibiofilm properties.

    Science.gov (United States)

    Ferreira, Susana; Domingues, Fernanda

    2016-10-01

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phytoalexin synthesized by plants in response to stress. This compound has several beneficial documented properties, namely anti-inflammatory, antioxidant, neuroprotective and antimicrobial activities. In this study the antimicrobial activity of resveratrol against Listeria monocytogenes and Listeria innocua was investigated. Resveratrol had a minimum inhibitory concentration of 200 µg mL(-1) for the tested strains, with time-kill curves demonstrating bacteriostatic activity. Inhibition of biofilm formation was also assessed, with resveratrol strongly inhibiting biofilm formation by both species even at subinhibitory concentrations. Overall, resveratrol showed antimicrobial properties on planktonic cells and on biofilm formation ability. Considering the potential use of resveratrol as a food preservative, the antimicrobial efficacy of resveratrol in food was studied in milk, lettuce leaf model and chicken juice. Resveratrol retained greater efficacy in both lettuce leaf model and chicken juice, but milk had a negative impact on its antilisterial activity, indicating a possible reduction of resveratrol availability in milk. This study reinforces resveratrol as an antimicrobial agent, pointing out its antibiofilm activity and its potential use as preservative in some food matrices. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. Regulatory effects of resveratrol on glucose metabolism and T-lymphocyte subsets in the development of high-fat diet-induced obesity in C57BL/6 mice.

    Science.gov (United States)

    Wang, Bin; Sun, Jin; Li, Longnan; Zheng, Jing; Shi, Yonghui; Le, Guowei

    2014-07-25

    High-fat diet (HFD)-induced obesity is often associated with immune dysfunction. Resveratrol (trans-3,5,4'-trihydroxystilbene), which has well-founded immunity-related beneficial properties, was used to elucidate the regulatory effect on glucose metabolism and T-lymphocyte subsets in the development of HFD-induced obesity. Resveratrol, being associated with decreases of plasma leptin and plasma lipids and the release of oxidative stress, significantly decreased the body weight and fat masses in HF mice after 26 weeks of feeding. Furthermore, resveratrol decreased the fasting blood glucose and fasting plasma insulin and increased the CD3(+)CD4(+)/CD3(+)CD8(+) subsets percentages and the regulatory T cells (Tregs) production after 13 and 26 weeks of feeding. The results indicate that resveratrol, as an effective supplement for HFD, maintained glucose homeostasis by activating the PI3K and SIRT1 signaling pathways. Moreover, resveratrol activated the Nrf2 signaling pathway-mediated antioxidant enzyme expression to alleviate inflammation by protecting against oxidative damage and T-lymphocyte subset-related chronic inflammatory response in the development of HFD-induced obesity.

  9. 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.

    Science.gov (United States)

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

    2014-09-01

    We investigated whether the inflammatory response and delayed onset of muscle soreness after a marathon are altered by resveratrol, a natural polyphenolic flavonoid antioxidant. Double blind placebo-controlled randomised pilot study. London Marathon. Marathon race participants. 7 healthy male athletes were randomised to receive Resveratrol (600 mg Resveratrol daily for 7 days immediately before the marathon) or a placebo. Blood samples taken 48 hours before and 18-32 hours after the marathon were analysed for white blood cell count (WBC) and C-reactive protein (CRP). A VAS score was taken at the same times as the blood samples to assess delayed onset muscle soreness. There were no significant differences between the two groups in terms of changes occurring between pre- and post- tests for WBC, CRP or VAS. There were no differences in immune response or delayed onset muscle soreness between resveratrol and placebo after a marathon. Further investigations are needed with longer treatment time and higher doses, analysing additional parameters such interleukins for a possible effect of resveratrol on the inflammatory response due to extensive exercise. To avoid a type II error, 17 subjects in each group would be required.

  10. Resveratrol protects cortical neurons against microglia-mediated neuroinflammation.

    Science.gov (United States)

    Zhang, Feng; Wang, Hui; Wu, Qin; Lu, Yuanfu; Nie, Jing; Xie, Xiaolong; Shi, Jingshan

    2013-03-01

    Neuroinflammation is closely associated with the pathogenesis of neurological disorders. The hallmark of neuroinflammation is considered to be microglial activation. Therefore, inhibition of microglial activation might hold a promising therapy for neurological disorders. Resveratrol, a natural non-flavonoid polyphenol found in grapes and red wine, has been recognized as a bioactive agent with potential benefit for health. Several lines of evidence show that resveratrol could exert neuroprotection against ischemia, seizure, and neurodegenerative diseases. However, the mechanisms underlying its beneficial neuroprotective effects are poorly defined. Here, by using rat primary cortical neuron-glia cultures, results showed that resveratrol attenuated lipopolysaccharide (LPS)-induced cortical neurotoxicity. Further studies revealed that microglia were responsible for resveratrol-mediated neuroprotection. Resveratrol significantly inhibited LPS-induced microglial activation and subsequent production of multiple pro-inflammatory and cytotoxic factors such as tumor necrosis factor-α, nitric oxide, and interleukin-1β. Collectively, resveratrol produced neuroprotection against microglia-induced neurotoxicity. Thus, resveratrol might represent a potential benefit for the treatment of inflammation-related neurological disorders. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Neuroprotective effects of Resveratrol in Alzheimer Disease Pathology

    Directory of Open Access Journals (Sweden)

    Shraddha D Rege

    2014-09-01

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

  12. 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.

  13. 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.

  14. Resveratrol Reverses Functional Chagas Heart Disease in Mice.

    Directory of Open Access Journals (Sweden)

    Glaucia Vilar-Pereira

    2016-10-01

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

  15. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

    To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs...

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

    International Nuclear Information System (INIS)

    Magalhaes, Vanessa D.; Rogero, Sizue O.; Vieira, Daniel P.; Okazaki, Kayo; Rogero, Jose R.; Cruz, Aurea S.

    2013-01-01

    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)

  17. 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)

  18. What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

    Science.gov (United States)

    Vang, Ole; Ahmad, Nihal; Baile, Clifton A.; Baur, Joseph A.; Brown, Karen; Csiszar, Anna; Das, Dipak K.; Delmas, Dominique; Gottfried, Carmem; Lin, Hung-Yun; Ma, Qing-Yong; Mukhopadhyay, Partha; Nalini, Namasivayam; Pezzuto, John M.; Richard, Tristan; Shukla, Yogeshwer; Surh, Young-Joon; Szekeres, Thomas; Szkudelski, Tomasz; Walle, Thomas; Wu, Joseph M.

    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 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. PMID:21698226

  19. Elicitor Mixtures Significantly Increase Bioactive Compounds, Antioxidant Activity, and Quality Parameters in Sweet Bell Pepper

    Directory of Open Access Journals (Sweden)

    Lina Garcia-Mier

    2015-01-01

    Full Text Available Sweet bell peppers are greatly appreciated for their taste, color, pungency, and aroma. Additionally, they are good sources of bioactive compounds with antioxidant activity, which can be improved by the use of elicitors. Elicitors act as metabolite-inducing factors (MIF by mimic stress conditions. Since plants rarely experience a single stress condition one by one but are more likely to be exposed to simultaneous stresses, it is important to evaluate the effect of elicitors on plant secondary metabolism as mixtures. Jasmonic acid (JA, hydrogen peroxide (HP, and chitosan (CH were applied to fruits and plants of bell pepper as mixtures. Bioactive compounds, antioxidant activity, and quality parameters were evaluated. The assessed elicitor cocktail leads to an increase in the variables evaluated (P ≤ 0.05 when applied to mature fruits after harvest, whereas the lowest values were observed in the treatment applied to immature fruits. Therefore, the application of the elicitor cocktail to harvested mature fruits is recommended in order to improve bioactive compounds and the antioxidant activity of sweet bell peppers.

  20. 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.

  1. Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

    Science.gov (United States)

    Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

    2017-06-07

    The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

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

    International Nuclear Information System (INIS)

    Jeong, Min Ho; Jo, Young Rae; Yang, Kwang Mo; Jeong, Dong Hyeok; Lee, Chang Geun; Oh, Su Jung; Jeong, Soo Kyung; Jo, Wol Soon; Lee, Ki Won

    2014-01-01

    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)

  3. A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

    Directory of Open Access Journals (Sweden)

    Hashem Andishmand, Hamed Hamishehkar, Afshin Babazadeh, Arezou Taghvimi, Mohammad Amin Mohammadifar, Mahnaz Tabibiazar

    2017-03-01

    Full Text Available Background: Resveratrol effects on the prevention and treatment of colon cancer have been well documented recently, but low solubility, rapid absorption and metabolism of resveratrol limit its beneficial effects on colon cancer. Designing a formulation that enhances the solubility of resveratrol, protects resveratrol from oxidation and isomerization, and delivers it to the colon is a priority of food and drug industry. In this study, resveratrol-polyethylene glycol (PEG-loaded pectin-chitosan polyelectrolyte complex was designed as a colon targeted delivery system. Methods: The effects of adding PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI, zeta potential by particle size analyzer, and scanning electron microscopy (SEM. Encapsulation efficiency (EE, release of resveratrol in simulated gastrointestinal fluid, and different pHs were analyzed via High Performance Liquid Chromatography (HPLC. Antioxidant activity was measured by (2, 2-diphenyl-1-picryl-hydrazyl-hydrate DPPH free-radical method. Results: Results showed that colloidal stable micro-particles (725 ± 20 nm with PDI < 0.3 and zeta potential +27 ± 2 mV was formed in the ratio of 5:1 of pectin to chitosan w/v % after a 10-min sonication. Encapsulation efficiency was 81 ± 7 %. The reduction of antioxidant activity of resveratrol loaded micro-particles after one month was less than 13%. Micro-particles released about 33% of resveratrol in the simulated gastric and intestinal fluids. Conclusion: Two-thirds of the loaded resveratrol in Pectin-Chitosan complex reached colon. The developed system had enough specification for enriching fruit based drinks due to remarkable colloidal stability in the pH range of 3.5 to 4.5.

  4. Resveratrol food supplements

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-01-01

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

  5. 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.

  6. Resveratrol in medicinal chemistry: a critical review of its pharmacokinetics, drug-delivery, and membrane interactions.

    Science.gov (United States)

    Neves, A R; Lucio, M; Lima, J L C; Reis, S

    2012-01-01

    Resveratrol is a polyphenol that among other sources occurs in grapes and for this reason, red wines also contain considerable amounts of this compound. Resveratrol is thought to be responsible for the "French Paradox" which associates red wine consumption to the low incidence of cardiovascular diseases. The interest in resveratrol has increased due to its pharmacological effects that include cardio and neuroprotection and several other benefic actions (e.g. antioxidant, anti-inflammatory, anti-carcinogenic and anti-aging). Despite the therapeutic effects of resveratrol, its pharmacokinetic properties are not favorable since this compound has poor bioavailability being rapidly and extensively metabolized and excreted. To overcome this problem, drug delivery systems have been developed to protect and stabilize resveratrol and to enhance its bioavailability. Herein is presented an up-to-date revision covering the literature reported for nano and microformulations for resveratrol encapsulation that include liposomes, polymeric nanoparticles, solid lipid nanoparticles, lipospheres, cyclodextrins, polymeric microspheres, yeast cells carriers and calcium or zinc pectinate beads. Regarding the interaction of resveratrol with cell membranes, only few studies have been published so far. However, it is believed that this interaction can be implied in the biological activities of resveratrol since transmembranar proteins are one of its cellular targets. Indeed, resveratrol presents the capacity to modulate the membrane organization which may consequently affect the protein functionality. Therefore, the intracellular effects of resveratrol and the effects of this compound at the membrane level were also revised since their knowledge is essential for understanding the pharmacological and therapeutic activities of this bioactive compound.

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

    NARCIS (Netherlands)

    Berbée, Jimmy F. P.; Wong, Man C.; Wang, Yanan; van der Hoorn, José W. A.; Khedoe, Padmini P. S. J.; van Klinken, Jan B.; Mol, Isabel M.; Hiemstra, Pieter S.; Tsikas, Dimitrios; Romijn, Johannes A.; Havekes, Louis M.; Princen, Hans M. G.; Rensen, Patrick C. N.

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  9. 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 ...

  10. 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.

  11. Anti-inflammatory mechanisms of resveratrol in activated HMC-1 cells: pivotal roles of NF-kappaB and MAPK.

    Science.gov (United States)

    Kang, Ok-Hwa; Jang, Hye-Jin; Chae, Hee-Sung; Oh, You-Chang; Choi, Jang-Gi; Lee, Young-Seob; Kim, Jong-Hak; Kim, Youn Chul; Sohn, Dong Hwan; Park, Hyun; Kwon, Dong-Yeul

    2009-05-01

    Resveratrol is a phytoalexin polyphenolic compound found in various plants, including grapes, berries, and peanuts. Recently, studies have documented various health benefits of resveratrol including cardiovascular and cancer-chemopreventive properties. The aim of the present study was to demonstrate the effects of resveratrol on the expression of pro-inflammatory cytokines, as well as to elucidate its mechanism of action in the human mast cell line (HMC-1). Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) plus A23187 in the presence or absence of resveratrol. To study the possible effects of resveratrol, ELISA, RT-PCR, real-time RT-PCR, Western blot analysis, fluorescence, and luciferase activity assays were used in this study. Resveratrol significantly inhibited the PMA plus A23187-induction of inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Moreover, resveratrol attenuated cyclooxygenase (COX)-2 expression and intracellular Ca2+ levels. In activated HMC-1 cells, phosphorylation of extra-signal response kinase (ERK) 1/2 decreased after treatment with resveratrol. Resveratrol inhibited PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB degradation, and luciferase activity. Resveratrol suppressed the expression of TNF-alpha, IL-6, IL-8 and COX-2 through a decrease in the intracellular levels of Ca2+ and ERK 1/2, as well as activation of NF-kappaB. These results indicated that resveratrol exerted a regulatory effect on inflammatory reactions mediated by mast cells.

  12. Trans-resveratrol reduces cardiac oxidative stress in rats exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Melina Hauck

    2015-07-01

    Full Text Available Differences between reactive oxygen species and antioxidant defense system unbalance the redox status. The exposure to cigarette smoke can increase this imbalance. Trans-resveratrol is a polyphenol with great antioxidant action that reduces the oxidative stress. This study investigated the effect of the trans-resveratrol supplementation on the cardiac oxidative stress in rats exposed to cigarette smoke. Male Wistar rats were randomized into four groups: Control Group (CG, Exposure to Smoke Group (ESG, Antioxidant Group (AG and Exposure to Smoke plus Antioxidant Group (ESAG. Animals were exposed to cigarette smoke and supplemented with trans-resveratrol (6.0 mg kg-1 for two months. The lipid peroxidation (TBARS and the enzymatic activity of catalase (CAT were measured in the cardiac muscle. The ESG presented the highest lipid peroxidation level compared with CG (p < 0.001, AG (p < 0.001 and ESAG (p < 0.006. The CAT activity was higher in the AG (p < 0.001 and ESAG (p < 0.001 compared with CG. The ESG presented lower CAT activity compared with the ESAG (p < 0.001. The supplementation of Trans-resveratrol attenuated the cardiac oxidative stress and increased the activity of catalase. Our findings evidenced the cardioprotective effect of trans-resveratrol in rats exposed to cigarette smoke.

  13. Neuroprotective effect of resveratrol against scopolamine-induced cognitive impairment and oxidative stress in rats

    Directory of Open Access Journals (Sweden)

    Pushpalatha Bunadri

    2013-01-01

    Full Text Available The objective of this study was to examine the neuroprotective effect of resveratrol on cognitive impairment induced by scopolamine, a muscarinic antagonist, in rats. Memory impairment was induced by administration of scopolamine (1 mg/kg intraperitoneally. Cognitive functions were assessed using radial arm maze, an active avoidance paradigm. Oxidative stress parameters like malondialdehyde, catalase and superoxide dismutase were assessed and acetylcholinesterase activity was estimated. More working and reference memory errors in the radial arm maze test and fewer avoidances in the active avoidance test were observed with scopolamine in the 1 mg/kg i.p.-treated animals. This phenomenon is a clear indication of memory impairment. Oral administration of resveratrol (20 mg/kg inhibited the occurrence of higher working, reference memory errors and prevented the incidence of less avoidances. Resveratrol appeared to have exerted memory-enhancing effects by inhibiting acetylcholinesterase activity and prevented the rise in malondialdehyde levels and loss of antioxidant enzymes catalase and superoxide dismutase, showing antioxidant potential. Based on the above results of behavioral and biochemical studies, it can be concluded that resveratrol protected against scopolamine-induced loss of cognition. The results also indicate that resveratrol is an antioxidant and an acetylcholinesterase inhibitor, and it is likely that resveratrol’s protective effect is related to its antioxidant and cholinesterase inhibitory effects.

  14. Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis.

    Science.gov (United States)

    Poussier, Bertrand; Cordova, Alfredo C; Becquemin, Jean-Pierre; Sumpio, Bauer E

    2005-12-01

    In France, despite a high intake of dietary cholesterol and saturated fat, the cardiovascular death rate is one of the lowest among developed countries. This "French paradox" has been postulated to be related to the high red wine intake in France. The aim of this study was to determine the effects of resveratrol, a major polyphenol component of red wine, on vascular smooth muscle cell (SMC) proliferation in vitro. SMCs were exposed to 10(-6) to 10(-4) M resveratrol and cell proliferation was assessed by cell counting. Cell cycle analysis was done by treating cells with propidium iodide followed by flow-activated cell sorting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. We demonstrate that resveratrol inhibited bovine aortic SMC proliferation in a dose-dependent manner. The lowest concentration of resveratrol resulting in a significant decrease in SMC proliferation compared with control was 10(-5) M. By flow cytometry, we observed a block in the G1-S phase of the SMC cycle. Resveratrol treatment also resulted in a dose-dependent apoptosis of SMCs but had no effects on SMC morphology. The results indicated that vascular SMC proliferation could be inhibited by resveratrol through a block on G1-S phase and by an increase in apoptosis. It supports the conjecture that red wine consumption may have a beneficial effect on cardiovascular mortality. Our results suggest that resveratrol inhibits, in a dose-dependent manner, smooth muscle cell proliferation, which may help to partially explain a beneficial effect of wine drinking. This inhibition is related to an early block in the cell cycle and also to a dose-dependent apoptotic effect. The present study demonstrates that resveratrol not only is an indirect marker of a healthy life style and alimentation but may also be directly responsible for the French paradox.

  15. Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

    OpenAIRE

    Sendobry, Sandra M; Cornicelli, Joseph A; Welch, Kathryn; Bocan, Thomas; Tait, Bradley; Trivedi, Bharat K; Colbry, Norman; Dyer, Richard D; Feinmark, Steven J; Daugherty, Alan

    1997-01-01

    15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.PD 146176 inhibited rabbit reticulocyt...

  16. 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

  17. Resveratrol and Endothelial Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ning Xia

    2014-10-01

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

  18. Resveratrol Reverses Functional Chagas Heart Disease in Mice

    Science.gov (United States)

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

    2016-01-01

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

  19. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2018-01-11

    Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

  20. 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.

  1. EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Nádia Araújo Miguel

    2016-07-01

    Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

  2. Resveratrol: review on therapeutic potential and recent advances in drug delivery.

    Science.gov (United States)

    Pangeni, Rudra; Sahni, Jasjeet K; Ali, Javed; Sharma, Shrestha; Baboota, Sanjula

    2014-08-01

    Natural products have seen a wide range of acceptability for the prevention and treatment of diseases throughout history. Resveratrol, a member of the stilbene family, has been found to potentially exhibit anticancer, antiangiogenic, immunomodulatory and cardioprotective activities as well as being an antioxidant. This is in addition to its usefulness in the treatment of neurodegenerative disease, diabetes and cardiac ailments. Currently, various studies have revealed that resveratrol is a potential drug candidate with multi-spectrum therapeutic application. This review aims to describe the various studies supporting the wide range of pharmacological activities of resveratrol. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of resveratrol such as solubility, stability and bioavailability. Resveratrol demonstrated its ability to be a potential drug candidate for the treatment of different ailments due to its potent antioxidant properties. To improve the drug stability, increase the bioavailability and minimize side-effects of resveratrol, novel drug delivery systems have been formulated to bring this potential candidate to the first line of disease treatment.

  3. Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.

    Science.gov (United States)

    Bhattarai, Govinda; Poudel, Sher Bahadur; Kook, Sung-Ho; Lee, Jeong-Chae

    2016-01-01

    Resveratrol is an antioxidant and anti-inflammatory polyphenol. Periodontitis is induced by oral pathogens, where a systemic inflammatory response accompanied by oxidative stress is the major event initiating disease. We investigated how resveratrol modulates cellular responses and the mechanisms related to this modulation in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (hGFs). We also explored whether resveratrol protects rats against alveolar bone loss in an experimental periodontitis model. Periodontitis was induced around the first upper molar of the rats by applying ligature infused with LPS. Stimulating hGFs with 5μg/ml LPS augmented the expression of cyclooxygenase-2, matrix metalloproteinase (MMP)-2, MMP-9, and Toll-like receptor-4. LPS treatment also stimulated the production of reactive oxygen species (ROS) and the phosphorylation of several protein kinases in the cells. However, the expression of heme oxygenase-1 (HO-1) and nuclear factor-E2 related factor 2 (Nrf2) was inhibited by the addition of LPS. Resveratrol treatment almost completely inhibited all of these changes in LPS-stimulated cells. Specifically, resveratrol alone augmented HO-1 induction via Nrf2-mediated signaling. Histological and micro-CT analyses revealed that administration of resveratrol (5mg/kg body weight) improved ligature/LPS-mediated alveolar bone loss in rats. Resveratrol also attenuated the production of inflammation-related proteins, the formation of osteoclasts, and the production of circulating ROS in periodontitis rats. Furthermore, resveratrol suppressed LPS-mediated decreases in HO-1 and Nrf2 levels in the inflamed periodontal tissues. Collectively, our findings suggest that resveratrol protects rats from periodontitic tissue damage by inhibiting inflammatory responses and by stimulating antioxidant defense systems. The aims of this study were to investigate how resveratrol modulates cellular responses and the mechanisms related to this modulation in

  4. 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...... on atherosclerosis marker VCAM-1. Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation blunts most of these effects.......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...

  5. Dihydro-resveratrol-A potent dietary polyphenol

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-01

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

  6. Preformulation stability of trans-resveratrol and trans-resveratrol glucoside (Piceid).

    Science.gov (United States)

    Jensen, James S; Wertz, Christian F; O'Neill, Victoria A

    2010-02-10

    Resveratrol and resveratrol glucoside (piceid) were evaluated in a preformulation stability study. An HPLC assay was used for the analysis of stressed/reference samples. Samples of solid, crystalline material were held under the following conditions: 40 degrees C/75% RH (both open and protected), ambient fluorescent light (open), 70 degrees C (open), and exposed using a light cabinet to achieve ICH conditions for UV/fluorescent light. Both compounds were found to be stable out to 3 months for both accelerated and ambient conditions with negligible degradation. Exposure to UV and fluorescent light under ICH conditions did not significantly degrade the solid materials for UV exposure at 3 times the ICH limit and for fluorescent light exposure at 1 times the ICH limit. The results presented demonstrate crystalline resveratrol and piceid are stable solids. No evidence of oxidation of either material by atmospheric oxidants was seen. The data reported may help to clarify widely held beliefs that resveratrol is unstable and extremely sensitive to oxidation/degradation.

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

    Directory of Open Access Journals (Sweden)

    Susanne Schuster

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

  8. Prevention of injury by resveratrol in a rat model of adenine-induced ...

    African Journals Online (AJOL)

    The effect of 10, 15, and 20 mg/kg doses of resveratrol on the levels of parathyroid hormone, phosphorous, and fibroblast growth factor-23 (FGF-23) in rat urine samples after 2 months of adenine administration were analyzed using an auto-analyzer. Results: Resveratrol treatment significantly inhibited the adenine-mediated ...

  9. Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases.

    Science.gov (United States)

    Zordoky, Beshay N M; Robertson, Ian M; Dyck, Jason R B

    2015-06-01

    Cardiovascular disease is the leading cause of death worldwide. Despite advancements in diagnosis and treatment of cardiovascular disease, the incidence of cardiovascular disease is still rising. Therefore, new lines of medications are needed to treat the growing population of patients with cardiovascular disease. Although the majority of the existing pharmacotherapies for cardiovascular disease are synthesized molecules, natural compounds, such as resveratrol, are also being tested. Resveratrol is a non-flavonoid polyphenolic compound, which has several biological effects. Preclinical studies have provided convincing evidence that resveratrol has beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. Although not fully delineated, some of the beneficial cardiovascular effects of resveratrol are mediated through activation of silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and endogenous anti-oxidant enzymes. In addition to these pathways, the anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties of resveratrol contribute to its beneficial cardiovascular effects. Despite the promise of resveratrol as a treatment for numerous cardiovascular diseases, the clinical studies for resveratrol are still limited. In addition, several conflicting results from trials have been reported, which demonstrates the challenges that face the translation of the exciting preclinical findings to humans. Herein, we will review much of the preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular disease and provide information about the physiological and molecular signaling mechanisms involved. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes. Copyright © 2014

  10. A comprehensive review of the health perspectives of resveratrol.

    Science.gov (United States)

    Rauf, Abdur; Imran, Muhammad; Suleria, Hafiz Ansar Rasul; Ahmad, Bashir; Peters, Dennis G; Mubarak, Mohammad S

    2017-12-13

    Many natural products present in our diet, including flavonoids, can prevent the progression of cancer and other diseases. Resveratrol, a natural polyphenol present in various fruits and vegetables, plays an important role as a therapeutic and chemopreventive agent used in the treatment of various illnesses. It exhibits effects against different types of cancer through different pathways. It additionally exerts antidiabetic, anti-inflammatory, and anti-oxidant effects in a variety of cell types. Furthermore, the cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. Accordingly, this article presents an overview of recent developments in the use of resveratrol for the prevention and treatment of different diseases along with various mechanisms. In addition, the present review summarizes the most recent literature pertaining to resveratrol as a chemotherapeutic agent against multiple diseases and provides an assessment of the potential of this natural compound as a complementary or alternative medicine.

  11. Sirt3-Mediated Autophagy Contributes to Resveratrol-Induced Protection against ER Stress in HT22 Cells

    Directory of Open Access Journals (Sweden)

    Wen-Jun Yan

    2018-02-01

    Full Text Available Endoplasmic reticulum (ER stress occurring in stringent conditions is critically involved in neuronal survival and death. Resveratrol is a non-flavonoid polyphenol that has neuroprotective effects against many neurological disorders. Here, we investigated the potential protective effects of resveratrol in an in vitro ER stress model mimicked by tunicamycin (TM treatment in neuronal HT22 cells. We found that TM dose-dependently decreased cell viability and increased apoptosis, which were both significantly attenuated by resveratrol treatment. Resveratrol markedly reduced the expression or activation of ER stress-associated factors, including GRP78, CHOP, and caspase-12. The results of immunocytochemistry and western blot showed that resveratrol promoted autophagy in TM-treated cells, as evidenced by increased LC3II puncta number, bcelin1 expression and LC3II/LC3I ratio. Pretreatment with the autophagy inhibitor chloroquine could reduce the protective effects of resveratrol. In addition, the expression of Sirt3 protein and its downstream enzyme activities were significantly increased in resveratrol-treated HT22 cells. To confirm the involvement of Sirt3-mediated mechanisms, siRNA transfection was used to knockdown Sirt3 expression in vitro. The results showed that downregulation of Sirt3 could partially prevented the autophagy and protection induced by resveratrol after TM treatment. Our study demonstrates a pivotal role of Sirt3-mediated autophagy in mediating resveratrol-induced protection against ER stress in vitro, and suggests the therapeutic values of resveratrol in ER stress-associated neuronal injury conditions.

  12. Distinct Mechanisms Underlying Resveratrol-Mediated Protection from Types of Cellular Stress in C6 Glioma Cells.

    Science.gov (United States)

    Means, John C; Gerdes, Bryan C; Koulen, Peter

    2017-07-14

    The polyphenolic phytostilbene, trans -resveratrol, is found in high amounts in several types and tissues of plants, including grapes, and has been proposed to have beneficial effects in the central nervous system due to its activity as an antioxidant. The objective of the present study was to identify the mechanisms underlying the protective effects of resveratrol under conditions of oxidative stress or DNA damage, induced by the extracellularly applied oxidant, tert -butyl hydrogen peroxide, or UV-irradiation, respectively. In C6 glioma cells, a model system for glial cell biology and pharmacology, resveratrol was protective against both types of insult. Prevention of tau protein cleavage and of the formation of neurofibrillary tangles were identified as mechanisms of action of resveratrol-mediated protection in both paradigms of cellular damage. However, depending on the type of insult, resveratrol exerted its protective activity differentially: under conditions of chemically induced oxidative stress, inhibition of caspase activity, while with DNA damage, resveratrol regulated tau phosphorylation at Ser 422 . Results advance our understanding of resveratrol's complex impact on cellular signaling pathway and contribute to the notion of resveratrol's role as a pleiotropic therapeutic agent.

  13. Effects of Long-Term Feeding of the Polyphenols Resveratrol and Kaempferol in Obese Mice

    Science.gov (United States)

    Montero, Mayte; de la Fuente, Sergio; Fonteriz, Rosalba I.; Moreno, Alfredo; Alvarez, Javier

    2014-01-01

    The effect of the intake of antioxidant polyphenols such as resveratrol and others on survival and different parameters of life quality has been a matter of debate in the last years. We have studied here the effects of the polyphenols resveratrol and kaempferol added to the diet in a murine model undergoing long-term hypercaloric diet. Using 50 mice for each condition, we have monitored weight, survival, biochemical parameters such as blood glucose, insulin, cholesterol, triglycerides and aspartate aminotransferase, neuromuscular coordination measured with the rotarod test and morphological aspect of stained sections of liver and heart histological samples. Our data show that mice fed since they are 3-months-old with hypercaloric diet supplemented with any of these polyphenols reduced their weight by about 5–7% with respect to the controls fed only with hypercaloric diet. We also observed that mice fed with any of the polyphenols had reduced levels of glucose, insulin and cholesterol, and better marks in the rotarod test, but only after 1 year of treatment, that is, during senescence. No effect was observed in the rest of the parameters studied. Furthermore, although treatment with hypercaloric diets induced large changes in the pattern of gene expression in liver, we found no significant changes in gene expression induced by the presence of any of the polyphenols. Thus, our data indicate that addition of resveratrol or kaempferol to mice food produces an initial decrease in weight in mice subjected to hypercaloric diet, but beneficial effects in other parameters such as blood glucose, insulin and cholesterol, and neuromuscular coordination, only appear after prolonged treatments. PMID:25386805

  14. Resveratrol and cancer treatment: updates.

    Science.gov (United States)

    Jiang, Zhengdong; Chen, Ke; Cheng, Liang; Yan, Bin; Qian, Weikun; Cao, Junyu; Li, Jie; Wu, Erxi; Ma, Qingyong; Yang, Wei

    2017-09-01

    Cancer, a growing health problem worldwide, affects millions of people every year. The overall survival rates of most cancers have been prolonged owing to the efforts of clinicians and scientists. However, some tumors develop resistance to chemoradiotherapeutic agents, and the cancer research community continues to search for effective sensitizers. Resveratrol, a natural polyphenolic phytoalexin, has shown promising effects in inhibiting proliferation and cancer progression in several tumor models. However, its molecular mechanisms and applications in chemotherapy and radiotherapy have yet to be fully determined. In this concise review, we highlight the role and related molecular mechanisms of resveratrol in cancer treatment. In particular, we focus on the role of resveratrol in the tumor microenvironment and the sensitization of cancer cells for chemotherapy and radiotherapy. Resveratrol shows promising efficacies in cancer treatment and may be applied in clinical therapy, but it requires further clinical study. © 2017 New York Academy of Sciences.

  15. 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.

  16. A Colon Targeted Delivery System for Resveratrol Enriching in pH Responsive-Model

    DEFF Research Database (Denmark)

    Andishmand, Hashem; Hamishehkar, Hamed; Mohammadifar, Mohammad Amin

    2017-01-01

    V was formed in the ratio of 5:1 of pectin to chitosan w/v % after a 10-min sonication. Encapsulation efficiency was 81 ± 7 %. The reduction of antioxidant activity of resveratrol loaded micro-particles after one month was less than 13%. Micro-particles released about 33% of resveratrol in the simulated...... PEG, ultra-sonication time, pH, and pectin to chitosan ratio were investigated on particle size, polydispersity index (PDI), zeta potential by particle size analyzer, and scanning electron microscopy (SEM). Encapsulation efficiency (EE), release of resveratrol in simulated gastrointestinal fluid......, and different pHs were analyzed via High Performance Liquid Chromatography (HPLC). Antioxidant activity was measured by (2, 2-diphenyl-1-picryl-hydrazyl-hydrate) DPPH free-radical method. Results: Results showed that colloidal stable micro-particles (725 ± 20 nm) with PDI

  17. Resveratrol products resulting by free radical attack

    Science.gov (United States)

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

    2008-06-01

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

  18. trans-Resveratrol as A Neuroprotectant

    Directory of Open Access Journals (Sweden)

    Ellen L. Robb

    2010-03-01

    Full Text Available Epidemiological evidence indicates that nutritionally-derived polyphenols such as resveratrol (RES have neuroprotective properties. Administration of RES to culture media protects a wide variety of neuronal cell types from stress-induced death. Dietary supplementation of RES can ameliorate neuronal damage and death resulting from both acute and chronic stresses in rodents. The specific molecular mechanisms by which RES acts at the cellular level remain incompletely understood. However, many experimental data indicate that RES reduces or prevents the occurrence of oxidative damage. Here we discuss possible mechanisms by which RES might exert protection against oxidative damage and cell death. Evidence suggesting that RES’s chemical antioxidant potential is not sufficient explanation for its effects is discussed. Putative biological activities, including interactions with estrogen receptors and sirtuins are critically discussed. We provide a synthesis of how RES’s phytoestrogenic properties might mediate the neuronal stress resistance underlying its observed neuroprotective properties.

  19. Resveratrol: Chemoprevention with red wine

    OpenAIRE

    Arısan, Elif Damla; Palavan-Ünsal, Narçin

    2007-01-01

    According to epidemiological studies, western diet has disadvantages because of cancer prevalence more than Mediterranean or Asia people who consume more vegetables and fruits. Resveratrol (trans-3,4,5-trihydroxystilbene) which is highly found in grapes, berries has received attention for its potential chemopreventive and antitumor effects in experimental systems. Because of high resveratrol content, researchers noted that red wine has multidimensional benefits for ...

  20. Antioxidant cosmeto-textiles: skin assessment.

    Science.gov (United States)

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

    2013-05-01

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

  1. Resveratrol Derivative-Rich Melinjo Seed Extract Attenuates Skin Atrophy in Sod1-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Kenji Watanabe

    2015-01-01

    Full Text Available The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1 resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (Gnetum gnemon Linn seed extract (MSE contains trans-resveratrol (RSV and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related skin pathologies in mice. Orally MSE and RSV treatment reversed the skin thinning associated with increased oxidative damage in the Sod1−/− mice. Furthermore, MSE and RSV normalized gene expression of Col1a1 and p53 and upregulated gene expression of Sirt1 in skin tissues. In vitro experiments revealed that RSV significantly promoted the viability of Sod1−/− fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generation in vivo and in vitro leading to protecting skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related skin diseases caused by oxidative damages.

  2. The molecular targets of resveratrol.

    Science.gov (United States)

    Kulkarni, Sameer S; Cantó, Carles

    2015-06-01

    Resveratrol has emerged in recent years as a compound conferring strong protection against metabolic, cardiovascular and other age-related complications, including neurodegeneration and cancer. This has generated the notion that resveratrol treatment acts as a calorie-restriction mimetic, based on the many overlapping health benefits observed upon both interventions in diverse organisms, including yeast, worms, flies and rodents. Though studied for over a decade, the molecular mechanisms governing the therapeutic properties of resveratrol still remain elusive. Elucidating how resveratrol exerts its effects would provide not only new insights in its fundamental biological actions but also new avenues for the design and development of more potent drugs to efficiently manage metabolic disorders. In this review we will cover the most recent advances in the field, with special focus on the metabolic actions of resveratrol and the potential role of SIRT1 and AMPK. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Constanze Buhrmann

    2016-03-01

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

  4. 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.

  5. Resveratrol Attenuates Neurodegeneration and Improves Neurological Outcomes after Intracerebral Hemorrhage in Mice

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    Frederick Bonsack

    2017-08-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke with a substantial public health impact. Currently, there is no effective treatment for ICH. The purpose of the study was to evaluate whether the post-injury administration of Resveratrol confers neuroprotection in a pre-clinical model of ICH. To this end, ICH was induced in adult male CD1 mice by collagenase injection method. Resveratrol (10 mg/kg or vehicle was administered at 30 min post-induction of ICH and the neurobehavioral outcome, neurodegeneration, cerebral edema, hematoma resolution and neuroinflammation were assessed. The Resveratrol treatment significantly attenuated acute neurological deficits, neurodegeneration and cerebral edema after ICH in comparison to vehicle treated controls. Further, Resveratrol treated mice exhibited improved hematoma resolution with a concomitant reduction in the expression of proinflammatory cytokine, IL-1β after ICH. Altogether, the data suggest the efficacy of post-injury administration of Resveratrol in improving acute neurological function after ICH.

  6. Antioxidants successfully reduce ROS production in propionic acidemia fibroblasts.

    Science.gov (United States)

    Gallego-Villar, Lorena; Pérez, Belén; Ugarte, Magdalena; Desviat, Lourdes R; Richard, Eva

    2014-09-26

    Propionic acidemia (PA), caused by a deficiency of the mitochondrial biotin dependent enzyme propionyl-CoA carboxylase (PCC) is one of the most frequent organic acidurias in humans. Most PA patients present in the neonatal period with metabolic acidosis and hyperammonemia, developing different neurological symptoms, movement disorders and cardiac complications. There is strong evidence indicating that oxidative damage could be a pathogenic factor in neurodegenerative, mitochondrial and metabolic diseases. Recently, we identified an increase in ROS levels in PA patients-derived fibroblasts. Here, we analyze the capability of seven antioxidants to scavenge ROS production in PA patients' cells. Tiron, trolox, resveratrol and MitoQ significantly reduced ROS content in patients and controls' fibroblasts. In addition, changes in the expression of two antioxidant enzymes, superoxide dismutase and glutathione peroxidase, were observed in PA patients-derived fibroblasts after tiron and resveratrol treatment. Our results in PA cellular models establish the proof of concept of the potential of antioxidants as an adjuvant therapy for PA and pave the way for future assessment of antioxidant strategies in the murine model of PA. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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    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.

  8. Resveratrol and endometriosis: In vitro and animal studies and underlying mechanisms (Review).

    Science.gov (United States)

    Kolahdouz Mohammadi, Roya; Arablou, Tahereh

    2017-07-01

    Endometriosis is characterized by the existence of endometrial tissue and stroma exterior to the uterus. Despite the high prevalence, the etiology of endometriosis remains elusive. The search for the most promising compounds for treatment of endometriosis has led to the identification of resveratrol. Resveratrol, a plant-derived polyphenolic phytoalexin, demonstrates broad-spectrum health beneficial effects, including anti-proliferative, anti-inflammatory, antineoplastic and antioxidant. Because of these properties and its wide distribution in plants, resveratrol is proposed as a great potential to treat endometriosis. In animal models of endometriosis, resveratrol supplementation has displayed beneficial results as it decreased the number and volume of endometrial implants, suppressed proliferation, vascularization, inflammation, cell survival and increased apoptosis. On the other hand, resveratrol treatment in-vitro studies, reduced invasiveness of endometriotic stromal cells (ESCs) and suppressed their inflammatory responses. In this review, we will summarize the recent studies in in-vitro and animal studies on resveratrol and endometriosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

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    Jing Zhang

    2015-01-01

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

  10. SIRT1-dependent myoprotective effects of resveratrol on muscle injury induced by compression

    Directory of Open Access Journals (Sweden)

    Thomas eSin

    2015-10-01

    Full Text Available Our current understanding on the molecular mechanisms by which sustained compression induces skeletal muscle injury is very limited. This study aimed to test the hypothesis that activation of SIRT1 by the natural antioxidant resveratrol could deactivate apoptotic and catabolic signalling in skeletal muscle exposed to moderate compression. Two cycles of 6-hour constant pressure at 100 mmHg was applied to the tibialis region of right, but not left hindlimbs of Sprague Dawley rats pre-treated with DMSO (vehicle control or resveratrol with/without sirtinol. Skeletal muscle tissues lying underneath and spatially corresponding to the compressed sites were collected for analyses. Resveratrol prevented the compression-induced manifestations of pathohistological damages including elevations of the number of interstitial nuclei and area of interstitial space and ameliorated oxidative damages measured as 4-hydroxy-2-nonenal (4HNE and nitrotyrosine in skeletal muscle. In parallel, resveratrol augmented the expression level and activity of SIRT1 and phosphorylation levels of Foxo3a and Akt while suppressed the increases in protein abundances of p53, Bax, MAFbx and ubiquitin, enzymatic activities of caspase 3 and 20S proteasome, and apoptotic DNA fragmentation in the compressed muscle. These favourable myoprotective effects of resveratrol were diminished upon pharmacological blockade of SIRT1 by using sirtinol. These novel data support the hypothesis that the anti-apoptotic and anti-catabolic effects of resveratrol on compression injury in skeletal muscle required the action of SIRT1.

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

    Science.gov (United States)

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

    2016-08-01

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

  12. Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats

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    Zhiyan Tian

    2016-12-01

    Full Text Available Aims: To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ-induced diabetic rats and to explore the mechanisms of that phenomenon. Methods: Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15, Res group (normal Sprague Dawley rats treated with resveratrol, n = 15, diabetes mellitus group (DM group, n = 15 and DM + Res group (diabetic rats treat with resveratrol, n = 15. Streptozotocin (STZ was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor and BDNF (Brain Derived Neurotrophic Factor via western blotting analysis. Results: Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression. Conclusions: Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.

  13. Resveratrol Intake During Pregnancy and Lactation Modulates the Early Metabolic Effects of Maternal Nutrition Differently in Male and Female Offspring.

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    Ros, Purificación; Díaz, Francisca; Freire-Regatillo, Alejandra; Argente-Arizón, Pilar; Barrios, Vicente; Argente, Jesús; Chowen, Julie A

    2018-02-01

    Poor maternal nutrition can have detrimental long-term consequences on energy homeostasis in the offspring. Resveratrol exerts antioxidant and antiobesity actions, but its impact during development remains largely unknown. We hypothesized that resveratrol intake during pregnancy and lactation could improve the effects of poor maternal nutrition on offspring metabolism. Wistar rats received a low-fat diet (LFD; 10.2% kcal from fat) or high-fat diet (HFD; 61.6% kcal from fat), with half of each group receiving resveratrol in their drinking water (50 mg/L) during pregnancy and lactation. Body weight (BW) of dams was measured at treatment onset and weaning [postnatal day (PND) 21] and of pups at birth and PND21, at which time dams and pups were euthanized. Although HFD dams consumed more energy, their BW at the end of lactation was unaffected. Mean litter size was not modified by maternal diet or resveratrol. At birth, male offspring from HFD and resveratrol (HFD + R) dams weighed less than those from LFD and resveratrol (LFD + R) dams. On PND21, pups of both sexes from HFD dams weighed more, had more visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT), and had higher serum leptin levels than those from LFD dams. Resveratrol reduced BW, leptin, VAT, and SCAT, with females being more affected, but increased glycemia. Neuropeptide levels were unaffected by resveratrol. In conclusion, resveratrol intake during pregnancy and lactation decreased BW and adipose tissue content in offspring of dams on an HFD but did not affect offspring from LFD-fed dams, suggesting that the potential protective effects of resveratrol during gestation/lactation are diet dependent. Copyright © 2018 Endocrine Society.

  14. Recent advances of resveratrol in nanostructured based delivery systems and in the management of HIV/AIDS.

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    Singh, Gurinder; Pai, Roopa S

    2014-11-28

    Resveratrol, a natural polyphenolic compound present in trees, in peanuts, in grapevines and exhibited multiple pharmacological activities. Extensive research in last two decades suggested that resveratrol possesses anti-inflammatory, anti-cancer, anti-viral, anti-amyloid, anti-arthritic and antioxidant properties. Some clinical reports have proposed that resveratrol might be a potential candidate for the prevention and/or treatment of HIV/AIDS and synergistically enhances the anti-HIV-1 activity. Resveratrol is not toxic to cells, and by itself reduces viral replication by 20% to 30%. With almost 12% of the world population suffering from HIV/AIDS including its resurgence in the developed world, better management of this global threat is highly desired. Further, various studies demonstrated several issues associated with resveratrol which account for its poor systemic bioavailability (almost zero) due to rapid and extensive first pass metabolism and existence of enterohepatic recirculation. In order to improve bioavailability and cellular uptake of resveratrol, various strategies have been adopted to date which includes resveratrol prodrug and the development of nanostructured delivery systems. Besides, nanostructured delivery systems are also known to inhibit the P-glycoprotein (P-gp) efflux, reduced metabolism by gut cytochrome P-450 enzymes, and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. This review paper provides an updated bird's-eye view account on the publications and patents study on the recent novel approaches to deliver resveratrol in order to enhance oral bioavailability, overcome first pass metabolism and trounce enterohepatic recirculation to make resveratrol a therapeutically potent drug. Providing a relatively pithy overview, this paper thus presents recent advances of resveratrol for the treatment and prevention of HIV/AIDS. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Resveratrol improves vasoprotective effects of captopril on aortic remodeling and fibrosis triggered by renovascular hypertension.

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    Natalin, Henrique Melo; Garcia, Arthur Feierabend Engracia; Ramalho, Leandra Naira Zambeli; Restini, Carolina Baraldi Araujo

    2016-01-01

    Renin-angiotensin system triggers vascular remodeling and fibrosis during the renovascular hypertensive two-kidney, one-clip (2K1C) model by oxidative-stress-mediated mechanisms. Thus, we hypothesized that the chronic treatment with the polyphenolic antioxidant resveratrol would improve the vasoprotective effects promoted by the chronic treatment with the angiotensin-converting enzyme inhibitor (ACEi) captopril in 2K1C hypertensive rats. Our main objective was to evaluate the effects of the combined treatment with resveratrol and captopril on vascular remodeling and fibrosis in 2K1C rats. Male Wistar rats underwent to unilateral renal stenosis by 2K1C Goldblatt model. Six weeks after surgery, rat systolic blood pressure (SBP) was measured by indirect tail-cuff plethysmography. 2K1C rats were considered hypertensive when presenting SBP higher than 160 mmHg and underwent resveratrol (20 mg/kg), captopril (6 or 12 mg/kg), or resveratrol (20 mg/kg) combined with captopril (6 or 12 mg/kg) treatment for 3 weeks. Nine weeks after surgery, rat SBP was measured, and rat thoracic aorta was isolated for histological assays with hematoxylin/eosin or Picrosirius Red to evaluate aortic remodeling and fibrosis, respectively. Oral treatment of 2K1C hypertensive rats with resveratrol (20 mg/kg) combined with the dose-dependent ACEi captopril (6 and 12 mg/kg) resulted in lesser aortic thickening and reduced aortic fibrosis. Resveratrol (20 mg/kg) promoted a more expressive hypotensive effect with captopril (12 mg/kg) in 2K1C rats than the treatment with isolated captopril (12 mg/kg). Resveratrol improves the vasoprotective effects promoted by captopril on aortic remodeling and fibrosis during renovascular hypertension probably by synergic mechanisms involving antioxidant actions and nitric oxide generation. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Role of resveratrol in regulation of cellular defense systems against oxidative stress.

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    Truong, Van-Long; Jun, Mira; Jeong, Woo-Sik

    2018-01-01

    Resveratrol, a natural polyphenolic compound, is found in various kinds of fruits, plants, and their commercial products such as red wine. It has been demonstrated to exhibit a variety of health-promoting effects including prevention and/or treatment of cardiovascular diseases, inflammation, diabetes, neurodegeneration, aging, and cancer. Cellular defensive properties of resveratrol can be explained through its ability of either directly neutralizing reactive oxygen species/reactive nitrogen species (ROS/RNS) or indirectly upregulating the expression of cellular defensive genes. As a direct antioxidant agent, resveratrol scavenges diverse ROS/RNS as well as secondary organic radicals with mechanisms of hydrogen atom transfer and sequential proton loss electron transfer, thereby protecting cellular biomolecules from oxidative damage. Resveratrol also enhances the expression of various antioxidant defensive enzymes such as heme oxygenase 1, catalase, glutathione peroxidase, and superoxide dismutase as well as the induction of glutathione level responsible for maintaining the cellular redox balance. Such defenses could be achieved by regulating various signaling pathways including sirtuin 1, nuclear factor-erythroid 2-related factor 2 and nuclear factor κB. This review provides current understanding and information on the role of resveratrol in cellular defense system against oxidative stress. © 2017 BioFactors, 44(1):36-49, 2018. © 2017 International Union of Biochemistry and Molecular Biology.

  17. Study of acute ecotoxicity of Resveratrol in Daphnia similis irradiated and non-irradiated

    International Nuclear Information System (INIS)

    Ormenio, Matheus B.; Mazieiro, Joana S.; Rogero, Sizue O.; Rogero, José R. Rogero

    2017-01-01

    Resveratrol is synthesized by a wide variety of plants in response to ultraviolet (UV) radiation or action of certain pathogens. It is a compound with ability to protect cells from free radicals, responsible for the natural process of cellular aging. It is known that resveratrol has a radiomodifying effect, in addition to the antioxidant potential, anti-inflammatory, against cardiovascular diseases. The increasing use of resveratrol as a function of biological activities has led to concern about toxicity. In the ecotoxicological area, acute ecotoxicity tests are performed on aquatic organisms that lethal effects of certain substances and / or environmental samples. These tests are important in providing critical information for the development and adoption of criteria for improvement environmental quality. In these tests Cladoceras are widely used as test organisms due to their extreme susceptibility to toxicants in the environment and because they are easy to handle in the laboratory. In this study, it was used Daphnia similis to verify the toxic effect of resveratrol on this non-irradiated organism and irradiated with gamma radiation. First, toxicity studies of resveratrol and gamma Daphnia similis, where the lethal dose (LD50) of the 585.43 Gy radiation was determined and the EC50 concentration of resveratrol that causes immobility in 50% of the organisms in the assay, of 6.08 μM. Based on these data, the study will be continued to assess the toxic effect of radiation on organisms that have been exposed prior to resveratrol, i.e, to verify the radiomodifying effect of resveratrol

  18. The effect of Resveratrol flavonoid on learning and memory in passive avoidance and Y maze in diabetic rat

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    Sima Nasri

    2014-04-01

    Full Text Available Background: Diabetes type I is accompanied with disturbances in cognitive skills, memory and learning. In this research, we evaluated the effect of resveratrol chronic treatment on learning and memory in diabetic male rats. Material and Methods: Rats were divided into 4 groups: control, resveratrol-treated control, diabetic and resveratrol-treated diabetic groups. We used streptozotosin for inducing diabetes. Resveratrol (10mg/kg I.p. was administered for 8 weeks. For evaluation of learning and memory, passive avoidance test and Y-maze task were used. For Statistical analysis, SPSS software and paired T-test and one-way ANOVA were used. Results: Resveratrol decreased serum glucose in diabetic rats (P<0.01. In passive avoidance learning, there wasn’t any significant difference in initial latency between diabetic and treated- diabetic group. Also, a significant decrease of step latency was observed in diabetic and treated diabetic rats (P<0.01. In Y maze, Resveratrol improved alternation percentage in diabetic rats. Conclusion: Probably due to different mechanism of long term and short term memory, long term resveratrol treatment didn’t improve memory and learning in passive avoidance learning. In Y maze, method for determining the spatial memory, resveratrol improved spatial memory in diabetic rats. Resveratrol not only regulates glucose in diabetic rats but also it improves short term memory.

  19. Restoration of altered microRNA expression in the ischemic heart with resveratrol.

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    Partha Mukhopadhyay

    2010-12-01

    Full Text Available Resveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far.We explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches.Cardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target genes for the differentially expressed miRNA include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury.Rats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against ischemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or longevinex. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R mice.

  20. Divergent effects of resveratrol, a polyphenolic phytostilbene, on free radical levels and type of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A.

    Science.gov (United States)

    Galfi, Peter; Jakus, Judit; Molnar, Tamas; Neogrady, Susan; Csordas, Adam

    2005-02-01

    We investigated the effects of the polyphenolic phytostilbene resveratrol on the steady-state free radical (FR) concentration and mode of cell death induced by the histone deacetylase inhibitors butyrate and trichostatin A. (i) There was no correlation between cell death induction by butyrate or trichostatin A (TSA) and FR levels. (ii) Treatment with resveratrol or N-acetyl-l-cystein (NAC) of cells, in which the FR concentration was high, resulted in an almost complete reduction of FR levels. (iii) When, however, the cellular FR concentration was marginal, resveratrol caused a minor, and NAC a marked increase of FRs as well as of the extent of cell death. Thus, resveratrol and NAC acted as antioxidants only when the cellular FR levels were high, and acted as pro-oxidants when facing a low FR concentration. (iv) Since resveratrol and the antioxidant NAC exhibited analogous effects, it is concluded that the observed actions of resveratrol are due to polyphenolic redox reactions and not related to the stilbene moiety of the molecule. (v) The results indicate that the redox status of a given cell type plays an important role in determining whether resveratrol and other antioxidants promote cell death or protect cells from it.

  1. Enhanced MTT-reducing activity under growth inhibition by resveratrol in CEM-C7H2 lymphocytic leukemia cells.

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    Bernhard, David; Schwaiger, Wolfgang; Crazzolara, Roman; Tinhofer, Inge; Kofler, Reinhard; Csordas, Adam

    2003-06-10

    Inhibition of proliferation by resveratrol of CEM-C7H2 lymphocytic leukemia cells was paradoxically associated with an enhanced cellular 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-reducing activity. This phenomenon was most pronounced at the sub-apoptotic concentration range of 5-20 microM resveratrol. The results of our study show that the MTT-reducing activity can be increased by the polyphenolic antioxidant resveratrol without a corresponding increase in the number of living cells and that this occurs at a concentration range of the antioxidant which is not sufficient to induce apoptosis but suffices to slow down cell growth. This phenomenon appears to be restricted to proliferation inhibitors with antioxidant properties and is cell type-specific. Thus, in determining the effects of flavonoids and polyphenols on proliferation, in certain cell types this might represent a pitfall in the MTT proliferation assay.

  2. 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

  3. Resveratrol analogs: promising chemopreventive agents.

    Science.gov (United States)

    Ogas, Talysa; Kondratyuk, Tamara P; Pezzuto, John M

    2013-07-01

    Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target specificity in the nanomolar range. Aromatase inhibition was enhanced over 6000-fold by using 1,3-thiazole as the central ring of resveratrol. Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to selective QR1 induction with a CD value of 87 nM. Several derivatives have been selected for evaluation of synergistic effects. Preliminary results with pairs of compounds are promising and further experiments, in a constant multidrug manner, will allow us to create polygonograms for larger combinations of derivatives. The objective is to develop a highly efficacious cocktail of derivatives based on the structure of resveratrol. © 2013 New York Academy of Sciences.

  4. Effect of Antioxidants Supplementation on Aging and Longevity

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    Bartosz, Grzegorz

    2014-01-01

    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. PMID:24783202

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

    International Nuclear Information System (INIS)

    Wang Zhirong; Chen Yan; Labinskyy, Nazar; Hsieh Tzechen; Ungvari, Zoltan; Wu, Joseph M.

    2006-01-01

    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

  6. Yucca schidigera bark: phenolic constituents and antioxidant activity.

    Science.gov (United States)

    Piacente, Sonia; Montoro, Paola; Oleszek, Wieslaw; Pizza, Cosimo

    2004-05-01

    Two new phenolic constituents with unusual spirostructures, named yuccaols D (1) and E (2), were isolated from the MeOH extract of Yucca schidigera bark. Their structures were established by spectroscopic (ESIMS and NMR) analysis. The new yuccaols D and E, along with resveratrol (3), trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene (4), yuccaols A-C (5-7), yuccaone A (8), larixinol (9), the MeOH extract of Yucca schidigera bark, and the phenolic portion of this extract, were assayed for antioxidant activity by measuring the free radical scavenging effects using two different assays, namely, the Trolox Equivalent Antioxidant Capacity (TEAC) assay and the coupled oxidation of beta-carotene and linoleic acid (autoxidation assay). The significant activities exhibited by the phenolic fraction and its constituents in both tests show the potential use of Y. schidigera as a source of antioxidant principles.

  7. Metabolic effects of resveratrol: addressing the controversies.

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    Bitterman, Jacob L; Chung, Jay H

    2015-04-01

    Resveratrol, a polyphenol found in a number of plant-based foods such as red wine, has received a great deal of attention for its diverse array of healthful effects. Beneficial effects of resveratrol are diverse; they include improvement of mitochondrial function, protection against obesity and obesity-related diseases such as type-2 diabetes, suppression of inflammation and cancer cell growth and protection against cardiovascular dysfunction, just to name a few. Investigations into the metabolic effects of resveratrol are furthest along and now include a number of clinical trials, which have yielded mixed results. There are a number of controversies surrounding resveratrol that have not been resolved. Here, we will review these controversies with particular emphasis on its mechanism of metabolic action and how lessons from resveratrol may help develop therapies that harness the effects of resveratrol but without the undesirable properties of resveratrol.

  8. Resveratrol modulates response against acute inflammatory stimuli in aged mouse brain.

    Science.gov (United States)

    Palomera-Ávalos, V; Griñán-Ferré, C; Izquierdo, V; Camins, A; Sanfeliu, C; Canudas, A M; Pallàs, M

    2018-02-01

    With upcoming age, the capability to fight against harmful stimuli decreases and the organism becomes more susceptible to infections and diseases. Here, the objective was to demonstrate the effect of dietary resveratrol in aged mice in potentiating brain defenses against LipoPolySaccharide (LPS). Acute LPS injection induced a strong proinflammatory effect in 24-months-old C57/BL6 mice hippocampi, increasing InterLeukin (Il)-6, Tumor Necrosis Factor-alpha (Tnf-α), Il-1β, and C-X-C motif chemokine (Cxcl10) gene expression levels. Resveratrol induced higher expression in those cytokines regarding to LPS. Oxidative Stress (OS) markers showed not significant changes after LPS or resveratrol, although for resveratrol treated groups a slight increment in most of the parameters studies was observed, reaching signification for NF-kB protein levels and iNOS expression. However, Endoplasmic Reticulum (ER) stress markers demonstrated significant changes in resveratrol-treated mice after LPS treatment, specifically in eIF2α, BIP, and ATF4. Moreover, as described, resveratrol is able to inhibit the mechanistic Target of Rapamycin (mTOR) pathway and this effect could be linked to (eIF2α) phosphorylation and the increase in the expression of the previously mentioned proinflammatory genes as a response to LPS treatment in aged animals. In conclusion, resveratrol treatment induced a different cellular response in aged animals when they encountered acute inflammatory stimuli. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Resveratrol in the foodomics era: 1:25,000.

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    Khakimov, Bekzod; Engelsen, Søren Balling

    2017-09-01

    Resveratrol is probably the most investigated plant secondary metabolite ever. An epidemiological study known as the French paradox showed a correlation between red wine intake and low mortality due to coronary heart diseases, and the red wine substance resveratrol was claimed to play a key role. Since then, several hundred resveratrol studies have been conducted to demonstrate its antioxidant and other beneficial properties. In the foodomics era, considering a complex foodome including over 25,000 substances that make up the human diet, it appears to be outdated to pursue the hunt for biological activities one function/compound at a time. First, nature is multivariate, and the effect of any one molecule will have to be modulated by its carrying matrix, its bioavailability, and synergies with other molecules. Second, a large number of targeted studies have the tendency to become biased, as they tend to retain only the data that the researchers think are relevant and thus increase the chances of spurious correlations. In this concise review, we retrace the research toward a more inductive, holistic, and multivariate path. © 2017 New York Academy of Sciences.

  10. Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection

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    Yu-Cheng Li

    2016-10-01

    Full Text Available Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg, fluoxetine (20 mg/kg and pioglitazone (10 mg/kg were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.

  11. Targeting extracellular matrix remodeling in disease: Could resveratrol be a potential candidate?

    Science.gov (United States)

    Agarwal, Renu; Agarwal, Puneet

    2017-02-01

    Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.

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

    Science.gov (United States)

    Chen, Hao; Jin, Zhi-Liang; Xu, Hai

    2016-01-01

    To study the involvement of MAPK MEK/ERK signaling transduction pathway in the apoptosis process of SW620 tumor cell line and the inhibition effect of resveratrol. SW620 cell lines were divided into 5 groups, namely, control group, PD98059 group, low-dose resveratrol group, mid-dose resveratrol group and high-dose resveratrol group. The inhibition rate of cell proliferation was detected by MTT method. The expression of apoptotic molecules and MEK/ERK signaling pathway related proteins were assayed by real-time PCR and Western blotting. Compared with control group, the proliferation of cells treated with resveratrol was significantly inhibited. In the case of apoptotic molecules, the expression of Bax, Caspase 3 and Caspase 9 was increased significantly while the expression of anti-apoptotic molecule Bcl2 was decreased significantly in resveratrol groups with a dose-dependent manner. In the case of molecules in MEK/ERK signaling pathway, the expression of Ras, Raf, MEK and ERK1/2 was decreased significantly in resveratrol groups with a dose-dependent manner. PD98059 and resveratrol can effectively inhibit the proliferation of SW620 through inhibiting the MEK/ERK signaling pathway. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

  14. Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells.

    Science.gov (United States)

    Lin, Feng-Yan; Hsieh, Yi-Hsien; Yang, Shun-Fa; Chen, Chang-Tai; Tang, Chih-Hsin; Chou, Ming-Yung; Chuang, Yi-Ting; Lin, Chiao-Wen; Chen, Mu-Kuan

    2015-10-01

    Naturally occurring agents, such as resveratrol, have been determined to benefit health. Numerous studies have demonstrated that resveratrol has antioxidative, cardioprotective, and neuroprotective properties. However, the effect of resveratrol exerts on the metastasis of oral cancer cells remains unclear. In this study, we investigated the effect the anti-invasive activity of resveratrol on a human oral cancer cell line (SCC-9) in vitro and the underlying mechanisms. Cell viability was examined by MTT assay, whereas cell motility was measured by migration and wound-healing assays. Zymography, reverse-transcriptase polymerase chain reaction (PCR), and promoter assays confirmed the inhibitory effects of resveratrol on matrix metalloproteinase-9 (MMP-9) expression in oral cancer cells. We established that various concentrations (0-100 μM) of resveratrol inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration capacities of SCC-9 cells and caused no cytotoxic effects. Zymography and Western blot analyses suggested that resveratrol inhibited TPA-induced MMP-9 gelatinolytic activity and protein expression. In addition, the results indicated that resveratrol inhibited the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 and extracellular-signal-regulated kinase (ERK)1/2 involved in downregulating protein expression and the transcription of MMP-9. In summary, resveratrol inhibited MMP-9 expression and oral cancer cell metastasis by downregulating JNK1/2 and ERK1/2 signals pathways and, thus, exerts beneficial effects in chemoprevention. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Dietary Vitamin C, E and β-Carotene Intake Does Not Significantly Affect Plasma or Salivary Antioxidant Indices and Salivary C-Reactive Protein in Older Subjects.

    Science.gov (United States)

    Gawron-Skarbek, Anna; Guligowska, Agnieszka; Prymont-Przymińska, Anna; Godala, Małgorzata; Kolmaga, Agnieszka; Nowak, Dariusz; Szatko, Franciszek; Kostka, Tomasz

    2017-07-09

    It is not clear whether habitual dietary intake influences the antioxidant or inflammatory status. The aim of the present study was to assess the impact of antioxidative vitamins C, E, and β-carotene obtained from daily food rations on plasma and salivary Total Antioxidant Capacity (TAC), uric acid and salivary C-reactive protein (CRP). The study involved 80 older subjects (66.9 ± 4.3 years), divided into two groups: group 1 ( n = 43) with lower and group 2 ( n = 37) with higher combined vitamins C, E and β-carotene intake. A 24-h dietary recall was obtained from each individual. TAC was assessed simultaneously with two methods in plasma (Ferric Reducing Ability of Plasma-FRAP, 2.2-diphenyl-1-picryl-hydrazyl-DPPH) and in saliva (FRAS and DPPHS test). Lower vitamin C intake corresponded to higher FRAS. There were no other correlations between vitamins C, E or β-carotene intake and antioxidant indices. Salivary CRP was not related to any antioxidant indices. FRAS was decreased in group 2 ( p < 0.01) but no other group differences for salivary or for plasma antioxidant parameters and salivary CRP were found. Habitual, not extra supplemented dietary intake does not significantly affect plasma or salivary TAC and salivary CRP.

  16. 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.

  17. Phenolic constituents of Pulicaria undulata (L. C.A. Mey. sub sp. undulata (Asteraceae: Antioxidant protective effects and chemosystematic significances

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    Sameh R. Hussein

    2017-04-01

    Full Text Available One new naturally isoflavone compound, 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′-O-β-glucopyranoside (1 was isolated from the aqueous methanol extract (AME of Pulicaria undulata subsp. undulata, together with seven known compounds: kaempferol (2, kaempferol 3-O-β-glucoside (3, quercetin (4, quercetin 3-O-β-glucoside (5, quercetin 3-O-β-galactoside (6, quercetin 3,7-di OCH3 (7, and caffeic acid (8. Their structures were established through chemical (acid hydrolysis and spectral analysis (UV, NMR, and ESIM. The AME and some isolated compounds were evaluated as protective agents. Free radical scavenging using a microscaled 2,2-diphenyl-1-picrylhydrazyl assay was used to assess the direct antioxidant properties that were evaluated by the ability to protect murine Hepa1c1c7 liver cells against damage induced by the organic peroxide tert-butyl hydroperoxide. The neutral red uptake assay (NRU was used to record the activity. Results of the 2,2-diphenyl-1-picrylhydrazyl assay recorded differential scavenging properties in ascending order: 5,7,2′,3′,4′ penta hydroxyl isoflavone-4′-O-β-glucopyranoside>quercetin>quercetin 3-O-galactoside>caffeic acid>quercetin 3,7-di-OCH3>kaempferol with 50% inhibitory concentrations of 3.9 μM, 7.5 μM, 11.4 μM, 12.2 μM, 78.1 μM, and 252.3 μM, respectively. The antioxidative potential reveals the potency of AME, quercetin, and quercetin 3,7-di-OCH3. The latter compound showed full protection at 100 μM (33 μg/mL against the induced toxicant effect where the 50% effective concentration was calculated as 33.6±1.7 μM (11.1 μg/mL. In addition to quercetin, which was extensively shown previously as a cytoprotective agent, AME was less potent; it was capable of protecting 75% at 100 μg/mL with 50% effective concentration of 92.3±4 μg/mL. Moreover, the isolated flavonoids were found to be significantly chemosystematic markers.

  18. 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.

  19. Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice

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    Castillo-Pichardo Linette

    2013-01-01

    Full Text Available Abstract Background Resveratrol, a polyphenol from grapes and red wine has many health beneficial effects, including protection against cardiovascular and neurodegenerative diseases and cancer. However, our group and others have provided evidence for a dual cancer promoting or inhibitory role for resveratrol in breast cancer, dependent on estrogenic or antiestrogenic activities. Moreover, much of the inhibitory effects of resveratrol have been reported from studies with high non-physiological concentrations. Methods We investigated the effects of a range of concentrations (0.5, 5, 50 mg/kg body weight of resveratrol on mammary tumor development post-initiation, using immunocompromised mice. Results Our findings suggest promotion of mammary tumor growth and metastasis by resveratrol at all concentrations tested in tumors derived from the low metastatic estrogen receptor (ERα(-, ERβ(+ MDA-MB-231 and the highly metastatic ER(- MDA-MB-435 cancer cell lines. Additionally, the activity of the migration/invasion regulator Rac, which we have previously shown to be regulated by resveratrol in vitro, was measured in tumors from resveratrol treated mice. Our results show a significant induction of tumoral Rac activity and a trend in increased expression of the Rac downstream effector PAK1 and other tumor promoting molecules following resveratrol treatment. Conclusion Taken together, our findings implicate low concentrations of resveratrol in potential promotion of breast cancer. Therefore, this study illuminates the importance of further delineating resveratrol’s concentration dependent effects, particularly in breast cancer, before it can be tested in the clinic or used as a dietary supplement for breast cancer patients.

  20. 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.

  1. Resveratrol stimulates c-Fos gene transcription via activation of ERK1/2 involving multiple genetic elements.

    Science.gov (United States)

    Thiel, Gerald; Rössler, Oliver G

    2018-06-05

    The polyphenol resveratrol is found in many plant and fruits and is a constituent of our diet. Resveratrol has been proposed to have chemopreventive and anti-inflammatory activities. On the cellular level, resveratrol activates stimulus-regulated transcription factors. To identify resveratrol-responsive elements within a natural gene promoter, the molecular pathway leading to c-Fos gene expression by resveratrol was dissected. The c-Fos gene encodes a basic region leucine zipper transcription factor and is a prototype of an immediate-early gene that is regulated by a wide range of signaling molecules. We analyzed chromatin-integrated c-Fos promoter-luciferase reporter genes where transcription factor binding sites were destroyed by point mutations or deletion mutagenesis. The results show that mutation of the binding sites for serum response factor (SRF), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) significantly reduced reporter gene transcription following stimulation of the cells with resveratrol. Inactivation of the binding sites for signal transducer and activator of transcription (STAT) or ternary complex factors did not influence resveratrol-regulated c-Fos promoter activity. Thus, the c-Fos promoter contains three resveratrol-responsive elements, the cAMP response element (CRE), and the binding sites for SRF and AP-1. Moreover, we show that the transcriptional activation potential of the c-Fos protein is increased in resveratrol-stimulated cells, indicating that the biological activity of c-Fos is elevated by resveratrol stimulation. Pharmacological and genetic experiments revealed that the protein kinase ERK1/2 is the signal transducer that connects resveratrol treatment with the c-Fos gene. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. 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.

  3. Potential chemoprotective role of resveratrol against cisplatin induced testicular damage in mice.

    Science.gov (United States)

    Singh, Inderjeet; Goyal, Yasmeen; Ranawat, Pavitra

    2017-08-01

    Semen banking is often advised to male patients undergoing chemotherapy as the damage induced is profound and often irreversible. However, low success rates of assisted reproductive techniques (ART) using banked semen have led to the quest for alternative methods to treat chemotherapy-induced infertility. The present study therefore aimed to study the role of resveratrol against cisplatin induced testicular damage. Male albino mice were divided into five groups (n = 6 each), viz. normal control, resveratrol vehicle (4% ethanol), Cisplatin (7.5 mg/kg b.wt/week for 4 weeks), Resveratrol (1 mg/kg b.wt./orally for 28 days) and Resveratrol and Cisplatin combination group. Cisplatin treatment led to an increase in the activity of lactate dehydrogenase and an increase in the levels of lipid peroxidation. Glutathione levels were found to decrease with a concomitant increase in the levels of oxidized glutathione and altered status of antioxidant enzymes. Increased DNA fragmentation was also evident which was further confirmed by histopathological and FT-IR analysis. Resveratrol treatment in combination with cisplatin showed great promise in bringing down the damage statistics to near normal values in most of the parameters studied. Further studies in this direction are however needed to develop an alternative to current procedures adopted to treat chemotherapy-induced male infertility. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Resveratrol prevents the development of pathological cardiac hypertrophy and contractile dysfunction in the SHR without lowering blood pressure.

    Science.gov (United States)

    Thandapilly, Sijo J; Wojciechowski, Peter; Behbahani, John; Louis, Xavier L; Yu, Liping; Juric, Danijel; Kopilas, Melanie A; Anderson, Hope D; Netticadan, Thomas

    2010-02-01

    Cardiac hypertrophy is a compensatory enlargement of the heart in response to stress such as hypertension. It is beneficial in reducing stress placed on the heart. However, when the stress is of a chronic nature, it becomes pathological and leads to cardiac dysfunction and heart failure. Current treatments for hypertension and heart failure have proven beneficial but are not highly specific and associated with side effects. Accordingly, there is an important need for alternative strategies to provide safe and effective treatment. Ten-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were treated with resveratrol (2.5 mg/kg/day) for a period of 10 weeks. Systolic blood pressure, and cardiac structure and function were measured in all groups at different time points of resveratrol treatment. Oxidative stress was also determined in all groups after 10 weeks of resveratrol treatment. SHRs were characterized with high blood pressure and concentric hypertrophy from 15 weeks of age. Cardiac functional abnormalities were also evident in SHR from 15 weeks onwards. Resveratrol treatment significantly prevented the development of concentric hypertrophy, and systolic and diastolic dysfunction in SHR without lowering blood pressure. Resveratrol also significantly reduced the oxidative stress levels of cardiac tissue in SHR. Resveratrol treatment was beneficial in preventing the development of concentric hypertrophy and cardiac dysfunction in SHR. The cardioprotective effect of resveratrol in SHR may be partially mediated by a reduction in oxidative stress. Thus, resveratrol may have potential in preventing cardiac impairment in patients with essential hypertension.

  5. In vivo speciation studies and antioxidant properties of bromine in Laminaria digitata reinforce the significance of iodine accumulation for kelps.

    Science.gov (United States)

    Küpper, Frithjof C; Carpenter, Lucy J; Leblanc, Catherine; Toyama, Chiaki; Uchida, Yuka; Maskrey, Benjamin H; Robinson, Joanne; Verhaeghe, Elodie F; Malin, Gill; Luther, George W; Kroneck, Peter M H; Kloareg, Bernard; Meyer-Klaucke, Wolfram; Muramatsu, Yasuyuki; Megson, Ian L; Potin, Philippe; Feiters, Martin C

    2013-07-01

    The metabolism of bromine in marine brown algae remains poorly understood. This contrasts with the recent finding that the accumulation of iodide in the brown alga Laminaria serves the provision of an inorganic antioxidant - the first case documented from a living system. The aim of this study was to use an interdisciplinary array of techniques to study the chemical speciation, transformation, and function of bromine in Laminaria and to investigate the link between bromine and iodine metabolism, in particular in the antioxidant context. First, bromine and iodine levels in different Laminaria tissues were compared by inductively coupled plasma MS. Using in vivo X-ray absorption spectroscopy, it was found that, similarly to iodine, bromine is predominantly present in this alga in the form of bromide, albeit at lower concentrations, and that it shows similar behaviour upon oxidative stress. However, from a thermodynamic and kinetic standpoint, supported by in vitro and reconstituted in vivo assays, bromide is less suitable than iodide as an antioxidant against most reactive oxygen species except superoxide, possibly explaining why kelps prefer to accumulate iodide. This constitutes the first-ever study exploring the potential antioxidant function of bromide in a living system and other potential physiological roles. Given the tissue-specific differences observed in the content and speciation of bromine, it is concluded that the bromide uptake mechanism is different from the vanadium iodoperoxidase-mediated uptake of iodide in L. digitata and that its function is likely to be complementary to the iodide antioxidant system for detoxifying superoxide.

  6. Resveratrol and health from a consumer perspective

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Grunert, Klaus G

    2015-01-01

    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......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)Howshould resveratrol bemarketed as a new functional...

  7. Metabolism and pharmacokinetics of resveratrol and pterostilbene.

    Science.gov (United States)

    Wang, Pei; Sang, Shengmin

    2018-01-01

    Beneficial properties of resveratrol and pterostilbene, a dimethyl ether analog of resveratrol, have attracted increasing interest in recent years. Resveratrol and pterostilbene exhibit many pharmacological similarities and both of them are generally considered to be safe for human consumption. Beyond the structural and general bioactivity similarities between them, large amounts of data are now available to reveal the metabolic fate and pharmacological differences between them. Pterostilbene was found to be more metabolically stable and usually exhibited stronger pharmacological activities than that of resveratrol. As a contribution to clarify and compare aspects like metabolic stability and pharmacokinetics of resveratrol and pterostilbene, as well as explain the pharmacological similarities and differences between them, this review presents and compares recent data on the metabolism and pharmacokinetics of resveratrol and pterostilbene. © 2018 BioFactors, 44(1):16-25, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  8. Amino Acid Carbamates As Prodrugs Of Resveratrol.

    Science.gov (United States)

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

    2015-10-14

    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.

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

    Directory of Open Access Journals (Sweden)

    Jaromír Lachman

    2009-03-01

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

  10. Resveratrol and Lifespan in Model Organisms.

    Science.gov (United States)

    Pallauf, Kathrin; Rimbach, Gerald; Rupp, Petra Maria; Chin, Dawn; Wolf, Insa M A

    2016-01-01

    Resveratrol may possess life-prolonging and health-benefitting properties, some of which may resemble the effect of caloric restriction (CR). CR appears to prolong the lifespan of model organisms in some studies and may benefit human health. However, for humans, restricting food intake for an extended period of time seems impracticable and substances imitating the beneficial effects of CR without having to reduce food intake could improve health in an aging and overweight population. We have reviewed the literature studying the influence of resveratrol on the lifespan of model organisms including yeast, flies, worms, and rodents. We summarize the in vivo findings, describe modulations of molecular targets and gene expression observed in vivo and in vitro, and discuss how these changes may contribute to lifespan extension. Data from clinical studies are summarized to provide an insight about the potential of resveratrol supplementation in humans. Resveratrol supplementation has been shown to prolong lifespan in approximately 60% of the studies conducted in model organisms. However, current literature is contradictory, indicating that the lifespan effects of resveratrol vary strongly depending on the model organism. While worms and killifish seemed very responsive to resveratrol, resveratrol failed to affect lifespan in the majority of the studies conducted in flies and mice. Furthermore, factors such as dose, gender, genetic background and diet composition may contribute to the high variance in the observed effects. It remains inconclusive whether resveratrol is indeed a CR mimetic and possesses life-prolonging properties. The limited bioavailability of resveratrol may further impede its potential effects.

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

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    Fu-Chao Liu

    2015-01-01

    Full Text Available 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 reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed.

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

    Science.gov (United States)

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

    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 reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed. PMID:26161238

  13. Inhibitory effect of resveratrol on proteinuria, hypoalbuminemia and hyperlipidemia in nephritic rats.

    Science.gov (United States)

    Nihei, T; Miura, Y; Yagasaki, K

    2001-05-11

    The effect of resveratrol, a polyphenolic compound present in grapes and other plants, on proteinuria, hypoalbuminemia and hyperlipidemia was studied in rats with glomerulonephritis. The nephritis was induced by an intravenous injection of anti-rat kidney glomerular basement membrane rabbit antiserum. Nephritic rats were given oral intubation of resveratrol (5 mg/day/100 g body weight) for 14 days, while control nephritic rats as well as normal ones were similarly given vehicle alone. By resveratrol treatment, enlargement in liver and kidney due to nephritis induction was significantly reduced, together with partial restoration of nephritis-induced reduction in body weight gain. Both proteinuria and hypoalbuminemia, characteristic symptoms to nephrotic syndrome, were significantly remedied, that is, urinary protein excretion was suppressed and serum albumin concentration was increased by resveratrol treatment. Resveratrol also suppressed significantly hyperlipidemia incident to nephritis, the hypotriglyceridemic action being more prominent than the hypocholesterolemic one. From these results, resveratrol is suggested to be a potent anti-glomerulonephritic food factor capable of suppressing proteinuria, hypoalbuminemia and hyperlipidemia at the same time.

  14. Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis.

    Science.gov (United States)

    Zhu, Xiangyun; Wu, Chunhua; Qiu, Shanhu; Yuan, Xuelu; Li, Ling

    2017-01-01

    Although the regular consumption of resveratrol has been known to improve glucose homeostasis and reverse insulin resistance in type 2 diabetes mellitus (T2DM), the reported results are inconsistent. Thus, we aimed to assess the effects of resveratrol on glycemic control and insulin sensitivity among patients with T2DM. We searched for relevant articles published until June 2017 on PubMed-Medline, Embase, Cochrane Library, and Web of Science. Randomized controlled trials in T2DM patients administered with resveratrol as intervention were included. After study selection, quality assessment and data extraction were performed independently by two authors, and STATA and RevMan software were used for statistical analysis. Nine randomized controlled trials involving 283 participants were included. Meta-analysis showed that resveratrol significantly improved the fasting plasma glucose ( -0.29 mmol/l, 95% CI: -0.51, -0.06, p resveratrol supplementation doses of resveratrol may benefit management of T2DM.

  15. 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.

  16. Study of acute ecotoxicity of Resveratrol in Daphnia similis irradiated and non-irradiated; Estudo da toxicidade aguda do Resveratrol em Daphnia similis irradiadas e não irradiadas

    Energy Technology Data Exchange (ETDEWEB)

    Ormenio, Matheus B.; Mazieiro, Joana S.; Rogero, Sizue O.; Rogero, José R. Rogero, E-mail: matheus.ormenio@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Resveratrol is synthesized by a wide variety of plants in response to ultraviolet (UV) radiation or action of certain pathogens. It is a compound with ability to protect cells from free radicals, responsible for the natural process of cellular aging. It is known that resveratrol has a radiomodifying effect, in addition to the antioxidant potential, anti-inflammatory, against cardiovascular diseases. The increasing use of resveratrol as a function of biological activities has led to concern about toxicity. In the ecotoxicological area, acute ecotoxicity tests are performed on aquatic organisms that lethal effects of certain substances and / or environmental samples. These tests are important in providing critical information for the development and adoption of criteria for improvement environmental quality. In these tests Cladoceras are widely used as test organisms due to their extreme susceptibility to toxicants in the environment and because they are easy to handle in the laboratory. In this study, it was used Daphnia similis to verify the toxic effect of resveratrol on this non-irradiated organism and irradiated with gamma radiation. First, toxicity studies of resveratrol and gamma Daphnia similis, where the lethal dose (LD50) of the 585.43 Gy radiation was determined and the EC50 concentration of resveratrol that causes immobility in 50% of the organisms in the assay, of 6.08 μM. Based on these data, the study will be continued to assess the toxic effect of radiation on organisms that have been exposed prior to resveratrol, i.e, to verify the radiomodifying effect of resveratrol.

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

    Directory of Open Access Journals (Sweden)

    Matthias Riebel

    2015-09-01

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

  18. Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

    Science.gov (United States)

    Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

    2017-08-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Polydatin, a natural precursor of resveratrol, induces cell cycle arrest and differentiation of human colorectal Caco-2 cell

    Science.gov (United States)

    2013-01-01

    Background Human colon adenocarcinoma cells are resistant to chemotherapeutic agents, such as anthracyclines, that induce death by increasing the reactive oxygen species. A number of studies have been focused on chemo-preventive use of resveratrol as antioxidant against cardiovascular diseases, aging and cancer. While resveratrol cytotoxic action was due to its pro-oxidant properties. In this study, we investigate whether the Resveratrol (trans-3,5,49-trihydroxystilbene) and its natural precursor Polydatin (resveratrol-3-O-b-mono- D-glucoside, the glycoside form of resveratrol) combination, might have a cooperative antitumor effect on either growing or differentiated human adenocarcinoma colon cancer cells. Methods The polydatin and resveratrol pharmacological interaction was evaluated in vitro on growing and differentiated Caco-2 cell lines by median drug effect analysis calculating a combination index with CalcuSyn software. We have selected a synergistic combination and we have evaluated its effect on the biological and molecular mechanisms of cell death. Results Simultaneous exposure to polydatin and resveratrol produced synergistic antiproliferative effects compared with single compound treatment. We demonstrated that polydatin alone or in combination with resveratrol at 3:1 molar ratio synergistically modulated oxidative stress, cell cycle, differentiation and apoptosis. Worthy of note treatment with polydatin induced a nuclear localization and decreased expression of heat shock protein 27, and vimentin redistributed within the cell. Conclusions From morphological, and biochemical outcome we obtained evidences that polydatin induced a transition from a proliferative morphology to cell-specific differentiated structures and caused human CaCo-2 cell death by induction of apoptosis. Our data suggest the potential use of polydatin in combination chemotherapy for human colon cancer. PMID:24138806

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

    Science.gov (United States)

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

    2016-11-01

    Resveratrol (RES), a polyphenolic compound found in grape skins, is a potent antioxidant with broad health benefits. However, its utilization in food has been limited by its poor water solubility, instability, and low bioavailability. The purpose of this study is to improve the solubility, stability, and cellular uptake of RES by nanoencapsulation using chitosan (CS) and γ-poly (glutamic acid) (γ-PGA). The size of nanoparticles significantly decreases with a decrease in the CS/γ-PGA ratio (psolubility of RES increases 3.2 and 4.2 times before and after lyophilization by nanoencapsulation, respectively. Compared with non-nanoencapsulated RES, the nanoencapsulated RES tends to maintain its solubility and antioxidant activity during storage. CS/γ-PGA nanoencapsulation was able to significantly enhance the transport of RES across a Caco-2 cell monolayer (psolubility and antioxidant activity during storage. Therefore, CS/γ-PGA nanoencapsulation is found to be a potentially valuable technique for improving the solubility, stability, and cellular uptake of RES. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Inhibition of STAT3 Expression and Signaling in Resveratrol-Differentiated Medulloblastoma Cells

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    Li-Jun Yu

    2008-07-01

    Full Text Available In this study, the potential influence of resveratrol (3,5,4′-trihydroxy-trans-stilbene in signal transducer and activator of transcription 3 (STAT3 signaling of medulloblastoma cells was evaluated by checking the status of STAT3 signaling and its downstream gene expression in two medulloblastoma cell lines (UW228-2 and UW228-3 with and without resveratrol treatment. The results revealed that resveratrol induced neuronal differentiation of medulloblastoma cells. Signal transducer and activator of transcription 3 expression and phosphorylation were detected in normally cultured UW228-2 and UW228-3 cells that were apparently attenuated after resveratrol treatment. The expression of STAT3 downstream genes, survivin, cyclin D1, Cox-2, and c-Myc, was suppressed but Bcl-2 was enhanced by resveratrol. Meanwhile, the production and secretion of leukemia inhibitory factor, a STAT3 activator, became active in resveratrol-treated cells. To further ascertain the significance of STAT3 signaling for medulloblastoma cells, AG490, a selective inhibitor of STAT3 phosphorylation, was used to treat UW228-3 cells. Phosphorylation of STAT3 was inhibited by AG490 accompanied with growth suppression, differentiation-like changes, and down-regulation of survivin, cyclin D1, Cox-2, and c-Myc. Our data thus suggest the importance of STAT3 signaling in maintenance and survival of medulloblastoma cells. This signaling may be the major target of resveratrol. Enhanced leukemia inhibitory factor and Bcl-2 expressions in resveratrol-treated cells might reflect a compensatory response to the loss of STAT3 function.

  5. The short term effects of resveratrol on ischemia-reperfusion injury in rat testis.

    Science.gov (United States)

    Yuluğ, Esin; Türedi, Sibel; Karagüzel, Ersagun; Kutlu, Omer; Menteşe, Ahmet; Alver, Ahmet

    2014-03-01

    The purpose of this study was to identify changes taking place in the rat testis at the 24th hour of reperfusion following testicular torsion and to evaluate the effects of resveratrol (RSV), a powerful antioxidant, in preventing these changes using novel biochemical parameters and histopathology. Eighteen adult male rats were divided into three groups: Sham-operated (S), torsion/detorsion (T/D), and T/D+RSV groups. In the T/D group, testicular ischemia was achieved by rotating the left testis 720° clockwise for 4h. In the T/D+RSV group, 20mg/kg RSV was administered intraperitoneally 30 min before detorsion. All rats were sacrificed 24h after detorsion. Serum and tissue malondialdehyde (MDA) concentrations, ischemia modified albumin (IMA), total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and histopathological damage score were analyzed. Serum MDA, IMA, TOS, and OSI levels rose significantly in the T/D group. Serum MDA and IMA values were lower in the T/D+RES groups, but not significantly. OSI and TOS values were lower in the T/D+RES group, and the difference was significant. TAS values decreased significantly in the T/D group and rose in the T/D+RSV group, but not significantly. Ipsilateral tissue MDA values were significantly elevated in the T/D group and decreased in the T/D+RSV group, but not significantly. Apoptosis and histopathological damage increased significantly in the T/D group and decreased significantly in the T/D+RSV group. In the contralateral testis, apoptosis increased significantly in the T/D group. It decreased significantly in the T/D+RSV group. Our findings show that RSV had a protective effect against oxidative damage induced with a testicular T/D model, especially at the antiapoptotic and histopathological level. OSI may be a good guide to the clinical status of testicular T/D. © 2014.

  6. Resveratrol protects rabbits against cholesterol diet- induced ...

    African Journals Online (AJOL)

    ... groups compared to HFD group only. In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis. Keywords: Cholesterol diet, Lipidaemia, Rabbit; Resveratrol, LDL-c, HDL-c, TC, TG ...

  7. The impact of resveratrol in lipid bilayers

    DEFF Research Database (Denmark)

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

    mechanism is unspecific. However, there are only few biophysical studies regarding the impact of resveratrol on lipid membranes. Here, results from a neutron reflectometry investigation on solid supported di-palmitoyl-phosphatidyl-choline (DPPC) bilayers with incorporated resveratrol are presented. The data...

  8. The impact of resveratrol in lipid bilayers

    DEFF Research Database (Denmark)

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

    knowledge on its probable working mechanism is rare. In this biophysical study, neutron reflectometry was used to investigate the direct impact of resveratrol on lipid membranes with solid supported bilayers. When interacting with di- palmitoyl-phosphatidyl-choline (DPPC) bilayers, resveratrol accumulates...

  9. Monitoring trans-Resveratrol in Grape Berry Skins During Ripening and in Corresponding Wines by HPLC

    Directory of Open Access Journals (Sweden)

    Elisabeta I. Geana

    2015-01-01

    Full Text Available Trans-resveratrol (3,5,4’-trihydroxy-trans-stilbene is naturally present in the skin of grapes and therefore is expected to occur in grape products. Recently, there has been a renewal of interest in wine as medical treatment for various disorders. In this study, berry skins of five red grape varieties were analysed at weekly intervals for trans-resveratrol production, during 2012 and 2013 harvest. The obtained wines were also evaluated. Quantification of trans resveratrol in grape skin extracts and wines was carried out by high-performance liquid chromatography. Favourable viticultural climate during harvest in 2012 resulted in a higher content of trans-resveratrol. The highest trans-resveratrol content was in Pinot Noir and Feteasca Neagra grape varieties, both in berry skins and wines, while the lowest amounts were identified in Cabernet Sauvignon variety. We can conclude that there was a significant correlation between the content of trans-resveratrol in grape skins and that in the respective wine.

  10. Resveratrol supplementation did not improves cognition in patients with schizophrenia: results from a randomized clinical trial

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    KARINE ZORTEA

    2016-09-01

    Full Text Available Background: Schizophrenia is associated with psychotic experiences and cognitive deficits. Therefore, cognitive function is one of the most critical determinants of quality of life in this pathology. Resveratrol has been related with neuroprotective action but there are no studies evaluating resveratrol in schizophrenia. The objective of this study was to determine the efficacy of resveratrol supplementation on cognition in individuals with schizophrenia. Methods: This is a 1-month randomized, double-blind controlled trial (NCT 02062190, in which 19 men with diagnosis of schizophrenia, aged 18 to 65 years, were assigned to a resveratrol supplement group (200mg or placebo group (200mg, with a 1-month follow-up. Applying a series of cognitive tests assessed neuropsychology performance (Hopkins Verbal Learning Test, Stroop Color and Word Test, Weschler Adult Intelligence Scale and Brief Psychiatric Rating Scale assessed psychopathology severity. Results: There were no significant improvement in neuropsychology performance (episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention and mental flexibility and psychopathology severity after 1-month of resveratrol supplementation (p>0.05. Conclusion: In conclusion, we have shown that 1-month of a resveratrol supplementation (200 mg/day did not improve episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention and mental flexibility as compared with placebo in patients with schizophrenia.

  11. Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice.

    Science.gov (United States)

    Yao, Jun; Wei, Cheng; Wang, Jian-Yao; Zhang, Ru; Li, Ying-Xue; Wang, Li-Sheng

    2015-06-07

    To determine the therapeutic efficacy of resveratrol on ulcerative colitis (UC) and its underlying mechanisms. The mouse UC model was developed using 5% dextran sulfate sodium. Mice were randomly divided into four groups: normal control, UC model group, resveratrol low-dose group (RLD; 50 mg/kg per day), and resveratrol high-dose group (RHD; 100 mg/kg per day). The results showed that RLD regulates Treg/Th17 balance mainly through reducing the number of Th17 cells, whereas RHD regulates Treg/Th17 balance through both downregulating the number of Th17 cells and upregulating the number of Treg cells. Resveratrol can also regulate the level of plasma and intestinal mucosal cytokines including interleukin (IL)-10, transforming growth factor-β1, IL-6, and IL-17. The expressions of hypoxia inducible factor (HIF)-1α, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 were significantly decreased in the intestinal tissues of mice treated with resveratrol. The therapeutic efficacy of resveratrol in UC is dose dependent and closely associated with the regulation of Treg/Th17 balance and the HIF-1α/mTOR signaling pathway.

  12. Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer.

    Science.gov (United States)

    Bartolacci, Caterina; Andreani, Cristina; Amici, Augusto; Marchini, Cristina

    2018-01-01

    It is an acknowledged fact that health benefits are derived from fruit- and vegetables-enriched diets. In particular, polyphenols, compounds bearing one or more hydroxyl groups attached to an aromatic ring, are ascribed for most of such beneficial effects. Among them, resveratrol, a phytoalexin found in numerous plant species, and more notably in grapes, has widely piqued the interest of the scientific community by virtue of its anti-aging, anti-inflammatory and anti-oxidant properties. Moreover, evidence claiming resveratrol ability to hinder processes underlying all the three steps of carcinogenesis (tumor initiation, progression and metastasization) has propelled an incredibly massive number of studies aimed at enquiring its eventual clinical potential in the fight against cancer. However, despite a large body of data pointing to the advantages of dietary resveratrol intake in respect of certain disease conditions, and cancer inter alia, its real position still remains quite ambiguous. In this uncertain scenario, the present review focuses its attention on the highly entangled relationship between resveratrol and breast cancer, attempting to shape the plethora of controversial results stemming from studies carried out on several in vitro and in vivo breast cancer models. Coping with such a tricky matter, there are so many variabilities concerning both resveratrol itself (dosage, administration, bioavailabilty, among others) and the unique molecular traits of each specific breast cancer subtype that must be taken into account when facing the dilemma: "might resveratrol be protective against breast cancer or does it rather fuel it?". Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Resveratrol Promotes Remyelination in Cuprizone Model of Multiple Sclerosis: Biochemical and Histological Study.

    Science.gov (United States)

    Ghaiad, Heba R; Nooh, Mohammed M; El-Sawalhi, Maha M; Shaheen, Amira A

    2017-07-01

    Multiple sclerosis (MS) is a demyelinating neurodegenerative disease, representing a major cause of neurological disability in young adults. Resveratrol is a stilbenoid polyphenol, known to pass blood brain barrier and exhibit antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. Cuprizone model of MS is particularly beneficial in studying demyelination/remyelination. Our study examined the potential neuroprotective and pro-remyelination effects of resveratrol in cuprizone-intoxicated C57Bl/6 mice. Mice were fed with chow containing 0.7 % cuprizone for 7 days, followed by 3 weeks on 0.2 % cuprizone diet. Resveratrol (250 mg/kg/day, p.o.) was given for 3 weeks starting from the second week. At the end of the experiment, animals were tested on rotarod to evaluate changes in balance and motor coordination. Mice were then sacrificed to measure the brain content of glutathione, lipid peroxidation products, adenosine triphosphate, and phospho-inhibitory subunit of nuclear factor κB-α. The activities of cytochrome oxidase and superoxide dismutase were also assessed. The gene expression of myelin basic protein, 2',3'-cyclic nucleotide 3' phosphodiesterase, oligodendrocyte transcription factor-1 (Olig1), NF-κB p65 subunit, and tumor necrosis factor-α was also estimated. Luxol fast blue/periodic acid-Schiff stained brain sections were blindly scored to assess the myelin status. Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination, improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. Interestingly, resveratrol increased Olig1 expression that is positively correlated to active remyelination. The present study may be the first to indicate a pro-remyelinative effect for resveratrol which might represent a potential additive benefit in treating MS.

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

    Directory of Open Access Journals (Sweden)

    Gabriella Lopes DE REZENDE BARBOSA

    2016-01-01

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

  15. 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)

  16. 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

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

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    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

  18. The Effects of Resveratrol Supplementation in Overweight and Obese Humans: A Systematic Review of Randomized Trials.

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    Christenson, Julia; Whitby, Serena J; Mellor, Duane; Thomas, Jackson; McKune, Andrew; Roach, Paul D; Naumovski, Nenad

    2016-09-01

    Obesity and metabolic syndrome are significant global health issues, with current public health messages predominately focused on altering dietary and physical activity behaviors. Resveratrol is a polyphenol (stilbenoid) commonly found in grapes, and human trials to date have shown conflicting and limited beneficial effects with respect to health. The aim of this study was to determine the effect of resveratrol supplementation on reducing body weight and modifying associated inflammatory markers. A systematic review was undertaken following the PRISMA guidelines and using five indexed databases (OVID MEDLINE, Cochrane Library, Web of Science, SCOPUS, and CINAHL). A search strategy was formulated to select randomized, double-blind, placebo-controlled human trials investigating the effects of resveratrol supplementation on obesity or overweight, including body weight, metabolic and inflammatory markers. Five thousand five hundred sixty-nine studies published from 1990 to November 2015 were identified, with only nine papers meeting the inclusion criteria. The studies involved 208 participants (aged 49.2 ± 8.3 years) and utilized a substantial range of resveratrol doses (75-3000 mg/day). Study durations were a minimum of 2 weeks (14-90 days). Seven studies indicated no significant change in body mass index or body weight (P > 0.05), and three studies showed no improvements in fat mass, fat volume, or abdominal fat distribution (P > 0.05). Four studies included measurements of inflammatory markers, with three of these finding resveratrol supplementation to have a significant positive effect (P > 0.05). Based on the included studies, there is currently insufficient evidence to support the recommendation of resveratrol supplements in management of obesity. However, there were significant but not entirely consistent anti-inflammatory effects after resveratrol supplementation in overweight and obese individuals.

  19. Rehabilitation Training and Resveratrol Improve the Recovery of Neurological and Motor Function in Rats after Cerebral Ischemic Injury through the Sirt1 Signaling Pathway

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    Na Shi

    2016-01-01

    Full Text Available This study was conducted to investigate the recovery of motor function in rats through the silent information regulator factor 2-related enzyme 1 (Sirt1 signal pathway-mediated rehabilitation training. Middle cerebral artery occlusion (MACO was used to induce ischemia/reperfusion injury. The rats were subjected to no treatment (model, rehabilitation training (for 21 days, resveratrol (5 mg/kg for 21 days, and rehabilitation training plus resveratrol treatment. 24 h later, They were assessed for neurobehavioral score and motor behavior score and expression of brain derived-nerve neurotrophic factor (BDNF and tyrosine kinase receptor B (TrkB. Compared with sham group, models had significantly higher neurobehavioral scores, balance beam, and rotary stick scores. Compared with the model group, rats in rehabilitation training and resveratrol groups had significantly reduced scores. Compared with rehabilitation training or resveratrol treatment alone, rehabilitation plus resveratrol further reduced the scores significantly. The percentage of cells expressing BDNF and TrkB and expression levels of BDNF and TrkB were similar between the model and sham groups, significantly increased in rehabilitation training and resveratrol groups, and further increased in rehabilitation training plus resveratrol group. These results indicate that rehabilitation raining plus resveratrol can significantly improve the recovery of motor function in rats after cerebral ischemic injury, which is likely related to the upregulation of the BDNF/TrkB signaling pathway.

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

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    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

  1. Effect of Resveratrol on the Prevention of Intra-Abdominal Adhesion Formation in a Rat Model

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    Guangbing Wei

    2016-06-01

    Full Text Available Background: Intra-abdominal adhesions are a very common complication following abdominal surgery. Our previous studies have demonstrated that the inhibition of inflammation at the sites of peritoneal injury can prevent the formation of intra-abdominal adhesions. Resveratrol is a natural extract with a broad range of anti-inflammatory effects. Therefore, we propose that resveratrol can reduce the formation of intra-abdominal adhesions after surgery. The aim of this study was to investigate the effect of resveratrol on intra-abdominal adhesion prevention in a rat model with surgery-induced peritoneal adhesions. Materials and Methods: The cecum wall and its opposite parietal peritoneum were abraded following laparotomy to induce intra-abdominal adhesion formation. Varying doses of resveratrol were administered to the animals. On the eighth day after surgery, the adhesion score was assessed using a visual scoring system. Picrosirius red staining and a hydroxyproline assay were used to assess the amount of collagen deposition in the adhesion tissues. The levels of serum interleukin-6 (IL-6, tumor necrosis factor (TNF-α, and transforming growth factor beta-1 (TGF-β1 were determined by an enzyme-linked immunosorbent assay (ELISA. Western blotting was performed to determine the protein expression of TGF-β1, fibrinogen, and α-smooth muscle actin (α-SMA in rat peritoneal adhesion tissue. Real-time RT-PCR was performed to quantify the mRNA expression of TGF-β1, fibrinogen, and α-SMA. Results: Resveratrol significantly reduced intra-abdominal adhesion formation and fibrin deposition in the rat model. Furthermore, resveratrol significantly reduced the serum levels of IL-6, TNF-α, and TGF-β1. The protein and mRNA expression of TGF-β1, fibrinogen, and α-SMA in the rat peritoneum and adhesion tissues were also down-regulated due to resveratrol intervention. Conclusion: Resveratrol can effectively prevent the formation of postoperative intra

  2. Changes in white adipose tissue metabolism induced by resveratrol in rats

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    Arias Noemí

    2011-05-01

    Full Text Available Abstract Background A remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue. Methods Sixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography. Results There was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue. Conclusions It can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.

  3. Wine Resveratrol: From the Ground Up

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    Luigi Bavaresco

    2016-04-01

    Full Text Available 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.

  4. Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic agent in an animal model, and a significant contributor to antioxidants in the European and American Diets.

    Science.gov (United States)

    Vinson, Joe A; Proch, John; Bose, Pratima; Muchler, Sean; Taffera, Pamela; Shuta, Donna; Samman, Najwa; Agbor, Gabriel A

    2006-10-18

    Chocolate today is often viewed as a food or snack with little nutritional value. The high saturated fat content of chocolate has also contributed to the belief that its consumption increases the risk of heart disease. However, recent human studies have proven that chocolate has beneficial effects on some pathogenic mechanisms of heart disease such as endothelial function and blood pressure. Although the antioxidant properties of chocolate have been known for some time, there has been no examination of its place in the U.S. diet as a source of antioxidants. This paper demonstrates that chocolate makes a significant contribution to U.S. per capita dietary antioxidants and by inference the European Community's. In the U.S. diet chocolate is the third highest daily per capita antioxidant source. An ex vivo study shows that epicatechin, a major polyphenol in chocolate and chocolate extracts, is a powerful inhibitor of plasma lipid oxidation due to polyphenols' ability to bind to lower density lipoproteins. Conversely, the fat from chocolate alone is a pro-oxidant in this model. This is also demonstrated in an in vivo human study. After consumption of dark chocolate and cocoa powder, the lower density lipoproteins isolated from plasma were protected from oxidation compared to the lipoproteins isolated after cocoa butter consumption, which were put under oxidative stress. In an animal model of atherosclerosis, cocoa powder at a human dose equivalent of two dark chocolate bars per day significantly inhibited atherosclerosis, lowered cholesterol, low-density lipoprotein, and triglycerides, raised high-density lipoprotein, and protected the lower density lipoproteins from oxidation. Chocolate has thus been shown to have potential beneficial effects with respect to heart disease.

  5. Effect of resveratrol and aerobic exercise on some cardiovascular risk factors in rats with acute myocardial infarction

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    Bahram Jamali Qarakhanlou

    2017-09-01

    Conclusion: Regular exercise and resveratrol supplementation is likely to be effective on cardiovascular risk factors and the combination of the two variables in the prevention of inflammation and will have a significant role in heart damage caused by myocardial infarction

  6. Resveratrol: anti-obesity mechanisms of action.

    Science.gov (United States)

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

    2014-11-14

    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.

  7. Elicitation of trans-resveratrol by laser resonant irradiation of table grapes

    Science.gov (United States)

    Jiménez Sánchez, J. B.; Crespo Corral, E.; Orea, J. M.; Santos Delgado, M. J.; González Ureña, A.

    2007-05-01

    Table grapes were irradiated with UV nanosecond laser pulses in searching for resonant photo-elicitation of trans-resveratrol, a known antioxidant compound naturally produced by grapevines and other plants. To this end, the irradiation time as well as the wavelength dependence of the induced trans-resveratrol content was investigated by comparing the elicitation level of this compound at two laser wavelengths. One wavelength was selected right at the maximum of the absorption band (302.1 nm, the resonant wavelength for this compound) while the second was selected (300 nm, a non-resonant wavelength) such that trans-resveratrol absorption is negligible. It was found that the resonant irradiation enhances the resveratrol content in grapes by up to six times more than that of non-resonant irradiation, the rest of the conditions being the same. This work demonstrates how selective laser excitation of fruits can open new possibilities for the development of functional foods with enhanced nutritional and beneficial properties.

  8. Resveratrol, in its natural combination in whole grape, for health promotion and disease management

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    Singh, Chandra K.; Liu, Xiaoqi; Ahmad, Nihal

    2015-01-01

    The grape antioxidant resveratrol has been a topic of intense research for the past three decades. Resveratrol and other grape ingredients, as well as whole-grape products, have shown considerable promise in health promotion and disease management. Phytochemically, whole grape represents a natural combination of resveratrol and other phytonutrients, as it contains several catechins, anthocyanins, polyphenols, and flavonols. Thus, the whole grape products or specific combinations of grape constituents provide us with the possibility of synergistic interactions leading to improved efficacy. Recent research has suggested that whole-grape products may help in maintaining heart health and protect against aging, aging-associated diseases, neurodegeneration, and some cancers. Based on the available recent literature, the grape or whole-grape products seem to be safer choices for better health and disease prevention. However, for advanced disease conditions, individual grape ingredients (such as resveratrol) or combinations of multiple ingredients together with existing therapies appear to be better approaches. Further clinical studies are needed to understand the benefits of grapes and their products in the prevention and management of specific diseases. PMID:26099945

  9. Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: a Review.

    Science.gov (United States)

    de Oliveira, Marcos Roberto; Chenet, Aline Lukasievicz; Duarte, Adriane Ribeiro; Scaini, Giselli; Quevedo, João

    2017-07-10

    Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss. Treatment with anti-depressants provides a complete remission of symptoms in approximately 50% of patients with major depression. However, these drugs may cause side effects, as sedation and weight gain. In this context, there is increasing interest in studies focusing on the anti-depressant effects of natural compounds found in the diet. Resveratrol is a polyphenolic phytoalexin (3,4',5-trihydroxystilbene; C 14 H 12 O 3 ; MW 228.247 g/mol) and has been found in peanuts, berries, grapes, and wine and induces anti-oxidant, anti-inflammatory, and anti-apoptotic effects in several mammalian cell types. Resveratrol also elicits anti-depressant effects, as observed in experimental models using animals. Therefore, resveratrol may be viewed as a potential anti-depressant agent, as well as may serve as a model of molecule to be modified aiming to ameliorate depressive symptoms in humans. In the present review, we describe and discuss the anti-depressant effects of resveratrol focusing on the mechanism of action of this phytoalexin in different experimental models.

  10. Resveratrol in prevention and treatment of common clinical conditions of aging

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    M Andrea Markus

    2008-06-01

    Full Text Available M Andrea Markus, Brian J MorrisSchool of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW, AustraliaAbstract: Resveratrol is a potent member of the class of natural, plant-derived chemicals known as polyphenols. These help explain in part why a diet high in fruit and vegetables confers health benefits and are associated with reduced risk of common complex conditions such as cardiovascular disease, cancer, diabetes, and Alzheimer’s disease. We present the latest molecular findings that account for the beneficial actions of resveratrol. The intracellular pathways activated are crucial for anti-oxidant defence, regulation of the cell cycle, mitochondrial energy production, vascular tone, oncogene suppression, and many other phenomena which if unchecked lead to morbidity and mortality from onset and progression of these various diseases. While a healthy diet and lifestyle is strongly recommended in prevention of such conditions, the future bodes well for the use of resveratrol and analogues of higher potency than the natural form for treatment of diseases that afflict humans, particularly as they age.Keywords: resveratrol, longevity, SIRT, wine, aging, cancer

  11. Resveratrol derivatives: an updated patent review (2012-2015).

    Science.gov (United States)

    Li, Chang; Xu, Xiaofei; Tao, Zhihao; Sun, Cuirong; Pan, Yuanjiang

    2016-08-04

    Resveratrol is a well-studied natural small molecule that possesses diverse bioactivities. Chemical derivation based on the resveratrol scaffold is of great importance to overcome the drawbacks of resveratrol and to improve its therapeutic potential. Continuous efforts have been established to develop resveratrol derivatives that target different therapeutic applications. This review covers patents published from 2012 to 2015. All resveratrol derivatives discussed are classified based on its derivation strategy as simple derivatives, conjugated derivatives and miscellaneous derivatives. Their therapeutic related activities are reviewed and discussed. Chemical derivation is an effective strategy to enhance the benefits of resveratrol and ameliorate its disadvantages. Recent studies on resveratrol derivatives have made great progress in the treatment of cancer and neurodegenerative diseases to name a few, demonstrating improved activity compared with resveratrol. Notably, its bioavailability was also improved in some cases. However, the 'next generation' of resveratrol derivatives still requires the development of new strategies and techniques.

  12. Resveratrol inhibits renal interstitial fibrosis in diabetic nephropathy by regulating AMPK/NOX4/ROS pathway.

    Science.gov (United States)

    He, Ting; Xiong, Jiachuan; Nie, Ling; Yu, Yanlin; Guan, Xu; Xu, Xinli; Xiao, Tangli; Yang, Ke; Liu, Liang; Zhang, Daohai; Huang, Yunjian; Zhang, Jingbo; Wang, Junping; Sharma, Kumar; Zhao, Jinghong

    2016-12-01

    Renal interstitial fibrosis is a major pathologic feature of diabetic nephropathy, while the pathogenesis and therapeutic interventions of diabetic renal interstitial fibrosis are not well established. In this study, we first demonstrated that high glucose could induce renal fibroblast (NRK-49F) cell proliferation and activation to myofibroblasts, accompanied by a significant increase in the intracellular levels of reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). ROS-mediated ERK1/2 activation was found to play a crucial role in high glucose-induced fibroblast proliferation and activation. Resveratrol, like the NOX4-targeting small interfering RNA (siRNA), markedly inhibited high glucose-induced fibroblast proliferation and activation by reducing NOX4-derived ROS production. It was then revealed that the increase in the expression of NOX4 induced by high glucose was due to the inactivation of AMP-activated protein kinase (AMPK), which could be reversed by resveratrol. Further in vivo investigation demonstrated that resveratrol treatment significantly attenuated renal fibrosis in db/db mice, accompanied by an evident increase in phospho-AMPK and decrease in NOX4. In summary, our results suggest that high glucose can directly promote renal fibroblasts proliferation and activation in a ROS-dependent manner, and resveratrol is a potential therapeutic agent against diabetic renal fibrosis via regulation of AMPK/NOX4/ROS signaling. Resveratrol inhibits high glucose-induced NRK cell activation by decreasing NOX4-derived ROS. Resveratrol inhibits high glucose-induced NOX4 expression in NRK cells via activation of AMPK. ROS-activated ERK1/2 signaling is involved in high glucose-induced NRK cell activation. Resveratrol attenuated renal fibrosis in db/db mice via regulation of AMPK/NOX4/ROS signaling.

  13. Trans-resveratrol induces a potential anti-lipogenic effect in lipopolysaccharide-stimulated enterocytes.

    Science.gov (United States)

    Etxeberria, U; Castilla-Madrigal, R; Lostao, M P; Martínez, J A; Milagro, F I

    2015-12-09

    A DNA microarray analysis was conducted in Caco-2 cells to analyse the protective effects of trans-resveratrol on enterocyte physiology and metabolism in pro-inflammatory conditions. Cells were pre-treated with 50 μΜ of trans-resveratrol and, subsequently, lipopolysaccharide (LPS) was added for 48 h. The microarray analysis revealed 121 genes differentially expressed between resveratrol-treated and non-treated cells (B> 0, is the odd thatthe gene is differentially expressed). Inhibitor of DNA binding 1 (ID1), histidine-rich glycoprotein (HRG), NADPH oxidase (NOX1) and sprouty homolog 1 (SPRY), were upregulated by LPS treatment, but significantly blocked by trans-resveratrol pre-treatment (padj< 0.05, after adjusting for Benjamini-Hocheberg procedure). Moreover, genes implicated in synthesis of lipids (z-score= -1.195) and concentration of cholesterol (z-score= -0.109), were markedly downregulated by trans-resveratrol. Other genes involved in fat turnover, but also in cell death and survival function, such as transcription factors Krüppel-like factor 5 (KLF5) and amphiregulin (AREG), were also significantly inhibited by trans-resveratrol pre-treatment. RT-qPCR-data confirmed the microarray results. Special mention deserves acyl-CoA synthetase long-chain family member 3 (ACSL3) and endothelial lipase (LIPG), which were downregulated by this stilbene and have been previously associated with fatty acid synthesis and obesity in other tissues. This study envisages that trans-resveratrol might exert an important anti-lipogenic effect at intestinal level under pro-inflammatory conditions, which has not been previously described.

  14. Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload.

    Science.gov (United States)

    Li, Wei; Wang, Yue-peng; Gao, Ling; Zhang, Peng-pai; Zhou, Qing; Xu, Quan-fu; Zhou, Zhi-wen; Guo, Kai; Chen, Ren-hua; Yang, Huang-tian; Li, Yi-gang

    2013-09-01

    To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms. Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes. H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

  15. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis

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    Xue - Fang Chen

    2013-06-01

    Full Text Available AIM: To investigate the protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis. METHODS:Subcultured human lens epithelial cell line, ultraviolet induced cell apoptosis, 20μmol/L resveratrol pretreated cell, the indicators change was observed: rate of apoptosis was detected by flow cytometry and apoptosis-related factors of caspses-3 and caspase-9 were detected by colorimetric detection, ultrastructure changes were observed under transmission electron microscope. RESULTS: Flow cytometry instrument testing found that resveratrol can suppress the apoptosis induced by ultraviolet irradiation, caspses-3 and caspase-9 content in positive control group were significantly higher than that of the negative control group at the same time period, the difference was statistically significant(P<0.05; caspses-3 and caspase-9 content in experimental group were lower than that in the positive control group at the same time, the difference was statistically significant(P<0.05. In addition, the damage of human lens epithelial cells was alleviated with the incubation time of resveratrol elongated. CONCLUSION:Resveratrol may inhibit ultraviolet-induced apoptosis of human lens epithelial cells, it has preventive function against radioactive cataract, and it can provide reliable evidence for pursuing effective medicine to prevent and treat cataract.

  17. Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells.

    Science.gov (United States)

    Sun, Zheng; Li, Hong; Shu, Xiao-Hong; Shi, Hui; Chen, Xiao-Yan; Kong, Qing-You; Wu, Mo-Li; Liu, Jia

    2012-07-01

    Glioblastoma multiforme (GBM) cells show different responses to resveratrol, for unknown reasons. Our data from human medulloblastoma cells and primary cultures of rat brain cells revealed an inverse correlation of sulfonation activity with resveratrol sensitivities, providing a clue to the underlying mechanisms of the variable sensitivities of GBM cells to resveratrol. In this study, we found that U251 cells were sensitive and LN229 cells were insensitive to resveratrol. Thus, these two cell lines were taken as comparable models for elucidating the influence of sulfonation activities on resveratrol sensitivity. HPLC showed identical resveratrol metabolic patterns in both cell lines. LC/MS and high-resolution mass MS analyses further demonstrated that resveratrol monosulfate generated by sulfotransferases (SULTs) was the major metabolite of human GBM cells. The levels of brain-associated SULT (SULT1A1, SULT1C2, and SULT4A1) expression in U251 cells were lower than those in LN229 cells, suggesting the inverse relationship of SULT-mediated sulfonation activity with high intracellular resveratrol bioavailability and resveratrol sensitivity of human GBM cells. Furthermore, immunohistochemical staining revealed reductions in expression of the three brain-associated SULTs in 72.8%, 47.5% and 66.3% of astrocytomas, respectively. Therefore, the levels of brain-associated SULTs and sulfonation activity mediated by them could be important parameters for evaluating the potential response of human GBM cells to resveratrol, and may have value in the personalized treatment of GBMs with resveratrol. © 2012 The Authors Journal compilation © 2012 FEBS.

  18. Resveratrol and Alzheimer's Disease: Mechanistic Insights.

    Science.gov (United States)

    Ahmed, Touqeer; Javed, Sehrish; Javed, Sana; Tariq, Ameema; Šamec, Dunja; Tejada, Silvia; Nabavi, Seyed Fazel; Braidy, Nady; Nabavi, Seyed Mohammad

    2017-05-01

    Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by progressive cognitive and memory deficits. The pathological hallmarks of AD include extracellular senile plaques and intracellular neurofibrillary tangles. Although several mechanisms have been used to explain the underlying pathogenesis of AD, current treatment regimens remain inadequate. The neuroprotective effects of the polyphenolic stilbene resveratrol (3,5,4'-trihydroxy-trans-stilbene) have been investigated in several in vitro and in vivo models of AD. The current review discusses the multiple potential mechanisms of action of resveratrol on the pathobiology of AD. Moreover, due to the limited pharmacokinetic parameters of resveratrol, multiple strategies aimed at increasing the bioavailability of resveratrol have also been addressed.

  19. Cellular Targets of Dietary Polyphenol Resveratrol

    Science.gov (United States)

    2006-09-01

    Resveratrol (trans-3,4 0,5-trihydroxystilbene) is a grape -derived polyphenol under intensive study for its potential in cancer pre- vention. In the case...to be slightly more sensitive to the grape -derived polyphenol thanFig. 1. Effects of resveratrol on growth of Line IV clone 1 and Line IV clone 3 human...melanoma cells [39,40]. Therefore, this grape -derived polyphenol should be further ex- plored for its potential in the prevention of human melanoma

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

    International Nuclear Information System (INIS)

    Takayanagi, Tsutomu; Okuda, Tohru; Mine, Yohei; Yokotsuka, Koki

    2004-01-01

    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)

  1. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

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    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  2. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

    Science.gov (United States)

    Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

    2008-01-01

    Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

  3. Resveratrol, Potential Therapeutic Interest in Joint Disorders: A Critical Narrative Review.

    Science.gov (United States)

    Nguyen, Christelle; Savouret, Jean-François; Widerak, Magdalena; Corvol, Marie-Thérèse; Rannou, François

    2017-01-06

    Trans-resveratrol (t-Res) is a natural compound of a family of hydroxystilbenes found in a variety of spermatophyte plants. Because of its effects on lipids and arachidonic acid metabolisms, and its antioxidant activity, t-Res is considered as the major cardioprotective component of red wine, leading to the "French Paradox" health concept. In the past decade, research on the effects of resveratrol on human health has developed considerably in diverse fields such as cancer, neurodegenerative and cardiovascular diseases, and metabolic disorders. In the field of rheumatic disorders, in vitro evidence suggest anti-inflammatory, anti-catabolic, anti-apoptotic and anti-oxidative properties of t-Res in various articular cell types, including chondrocytes and synoviocytes, along with immunomodulation properties on T and B lymphocytes. In preclinical models of osteoarthritis and rheumatoid arthritis, resveratrol has shown joint protective effects, mainly mediated by decreased production of pro-inflammatory and pro-degradative soluble factors, and modulation of cellular and humoral responses. Herein, we comprehensively reviewed evidence supporting a potential therapeutic interest of t-Res in treating symptoms related to rheumatic disorders.

  4. Resveratrol, Potential Therapeutic Interest in Joint Disorders: A Critical Narrative Review

    Directory of Open Access Journals (Sweden)

    Christelle Nguyen

    2017-01-01

    Full Text Available Trans-resveratrol (t-Res is a natural compound of a family of hydroxystilbenes found in a variety of spermatophyte plants. Because of its effects on lipids and arachidonic acid metabolisms, and its antioxidant activity, t-Res is considered as the major cardioprotective component of red wine, leading to the “French Paradox” health concept. In the past decade, research on the effects of resveratrol on human health has developed considerably in diverse fields such as cancer, neurodegenerative and cardiovascular diseases, and metabolic disorders. In the field of rheumatic disorders, in vitro evidence suggest anti-inflammatory, anti-catabolic, anti-apoptotic and anti-oxidative properties of t-Res in various articular cell types, including chondrocytes and synoviocytes, along with immunomodulation properties on T and B lymphocytes. In preclinical models of osteoarthritis and rheumatoid arthritis, resveratrol has shown joint protective effects, mainly mediated by decreased production of pro-inflammatory and pro-degradative soluble factors, and modulation of cellular and humoral responses. Herein, we comprehensively reviewed evidence supporting a potential therapeutic interest of t-Res in treating symptoms related to rheumatic disorders.

  5. Resveratrol, human health and winemaking perspectives.

    Science.gov (United States)

    Pastor, Raúl Francisco; Restani, Patrizia; Di Lorenzo, Chiara; Orgiu, Francesca; Teissedre, Pierre-Louis; Stockley, Creina; Ruf, Jean Claude; Quini, Claudia Inés; Garcìa Tejedor, Nuria; Gargantini, Raquel; Aruani, Carla; Prieto, Sebastián; Murgo, Marcelo; Videla, Rodolfo; Penissi, Alicia; Iermoli, Roberto Héctor

    2017-12-05

    Resveratrol, (3, 5, 4'-trihydroxystilbene) is a non-flavonoid polyphenol stilbene synthesized by plants when damaged by infectious diseases or ionizing radiation. Although present in more than seventy plant species, grapes and wine are the major dietary contributors of resveratrol, responsible for 98% of the daily intake. In 1992, Renaud and De Lorgeril first linked wine polyphenols, including resveratrol, to the potential health benefits ascribed to regular and moderate wine consumption (the so called "French Paradox"). Since then, resveratrol has received increasing scientific interest, leading to research on its biological actions, and to a large number of published papers, which have been collected and discussed in this review. The relatively low amounts of resveratrol measured in wine following moderate consumption, however, may be insufficient to mitigate biological damage, such as that due to oxidative stress. On this basis, the authors also highlight the importance of viticulture and the winemaking process to enhance resveratrol concentrations in wine in order to bolster potential health benefits.

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

    Directory of Open Access Journals (Sweden)

    Mozhgan Rezaie Kanavi

    2014-10-01

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

  7. Short-term high dose of quercetin and resveratrol alters aging markers in human kidney cells

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    Fatemeh Abharzanjani

    2017-01-01

    Full Text Available Background: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. Methods: Human embryonic kidney cell (HEK-293 was cultured in Dulbecco's Modified Eagle Medium (DMEM containing 100 mM (18 mg/L for 24 h. The cells were treated with resveratrol (2.5, 5, 10 μm, quercetin (3, 6, 12 μm, and combination of these (R 2.5 μm, Q 3 μm and (R 5 μm, Q 6 μm and (R 10 μm, Q 12 μm for 48 h, and then, cells were lysed to access RNA and lysate. Results: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. Conclusions: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

  8. 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.

  9. Red Wine and Resveratrol: Good for Your Heart?

    Science.gov (United States)

    Red wine and resveratrol: Good for your heart? Red wine and something in red wine called resveratrol might be heart healthy. Find out the facts, and hype, regarding red wine and its impact on your heart. By Mayo ...

  10. Melatonin Enhances Phenolics Accumulation Partially via Ethylene Signaling and Resulted in High Antioxidant Capacity in Grape Berries

    Directory of Open Access Journals (Sweden)

    Lili Xu

    2017-08-01

    Full Text Available This study assessed the primary impacts of exogenous melatonin (MT treatment on grape berry metabolism. Exogenous MT treatment increased the endogenous MT content and modified berry ripening. Transcriptomic analysis revealed that the processes of polyphenol metabolism, carbohydrate metabolism and ethylene biosynthesis and signaling were the three most significantly altered biological processes upon MT treatment. Further experiments verified that MT treatment increased the contents of total anthocyanins, phenols, flavonoids and proanthocyanidins in berries. Additionally, the contents of 18 of the 22 detected individual phenolic compounds were enhanced by MT treatment; particularly, the resveratrol content was largely increased concomitantly with the up-regulation of STS gene expression. Meanwhile, MT treatment enhanced the antioxidant capacity of berries. On the other hand, it was indicated that ethylene participated in the regulation of polyphenol metabolism and antioxidant capacity under MT treatment in grape berries. In summary, MT enhances the polyphenol content and antioxidant capacity of grape berries partially via ethylene signaling.

  11. Resveratrol Modulation of Protein Expression in parkin-Mutant Human Skin Fibroblasts: A Proteomic Approach

    Science.gov (United States)

    Gaballo, Antonio; Signorile, Anna; Tanzarella, Paola; Pacelli, Consiglia; Di Paola, Marco

    2017-01-01

    In this study, we investigated by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) analysis the effects of resveratrol treatment on skin primary fibroblasts from a healthy subject and from a parkin-mutant early onset Parkinson's disease patient. Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson's disease. Functional alteration of parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins accountable for the neurodegenerative process. The identification of proteins differentially expressed revealed that resveratrol treatment can act on deregulated specific biological process and molecular function such as cellular redox balance and protein homeostasis. In particular, resveratrol was highly effective at restoring the heat-shock protein network and the protein degradation systems. Moreover, resveratrol treatment led to a significant increase in GSH level, reduction of GSSG/GSH ratio, and decrease of reduced free thiol content in patient cells compared to normal fibroblasts. Thus, our findings provide an experimental evidence of the beneficial effects by which resveratrol could contribute to preserve the cellular homeostasis in parkin-mutant fibroblasts. PMID:29138676

  12. Resveratrol Modulation of Protein Expression in parkin-Mutant Human Skin Fibroblasts: A Proteomic Approach

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    Daniele Vergara

    2017-01-01

    Full Text Available In this study, we investigated by two-dimensional gel electrophoresis (2-DE and mass spectrometry (MS analysis the effects of resveratrol treatment on skin primary fibroblasts from a healthy subject and from a parkin-mutant early onset Parkinson’s disease patient. Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson’s disease. Functional alteration of parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins accountable for the neurodegenerative process. The identification of proteins differentially expressed revealed that resveratrol treatment can act on deregulated specific biological process and molecular function such as cellular redox balance and protein homeostasis. In particular, resveratrol was highly effective at restoring the heat-shock protein network and the protein degradation systems. Moreover, resveratrol treatment led to a significant increase in GSH level, reduction of GSSG/GSH ratio, and decrease of reduced free thiol content in patient cells compared to normal fibroblasts. Thus, our findings provide an experimental evidence of the beneficial effects by which resveratrol could contribute to preserve the cellular homeostasis in parkin-mutant fibroblasts.

  13. Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats

    Science.gov (United States)

    Navarro-Cruz, A. R.; Ramírez y Ayala, R.; Ochoa-Velasco, C.; Avila-Sosa, R.; Pérez-Fernández, S.; Morales-Medina, J. C.

    2017-01-01

    The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions. PMID:29163756

  14. 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.

  15. Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia

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    Yu-Chieh Su

    2013-01-01

    Full Text Available IL-6 and sonic hedgehog (Shh signaling molecules are considered to maintain the growth of cancer stem cells (CSCs. Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted.

  16. Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats

    Directory of Open Access Journals (Sweden)

    A. R. Navarro-Cruz

    2017-01-01

    Full Text Available The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions.

  17. Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.

    Science.gov (United States)

    Strunz, Célia Maria Cássaro; Roggerio, Alessandra; Cruz, Paula Lázara; Pacanaro, Ana Paula; Salemi, Vera Maria Cury; Benvenuti, Luiz Alberto; Mansur, Antonio de Pádua; Irigoyen, Maria Cláudia

    2017-02-01

    Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Resveratrol Protects and Restores Endothelium-Dependent Relaxation in Hypercholesterolemic Rabbit Corpus Cavernosum.

    Science.gov (United States)

    Murat, Nergiz; Korhan, Peyda; Kizer, Onur; Evcim, Sinem; Kefi, Aykut; Demir, Ömer; Gidener, Sedef; Atabey, Neşe; Esen, Ahmet Adil

    2016-01-01

    Oxidative stress dependent-decrease in nitric oxide (NO) bioavailability plays an integral role in hypercholesterolemia-induced erectile dysfunction (ED). Resveratrol has been demonstrated to exert beneficial effects against oxidative stress and improve NO bioavailability. The protective and restorative potentials of resveratrol on endothelium-dependent relaxations were evaluated in hypercholesterolemic rabbit corpus cavernosum (CC). Hypercholesterolemia was induced by administering 2% cholesterol diet (CD) (w/w) to the rabbits for 6 weeks. Two different protocols were applied to test the effects of resveratrol on hypercholesterolemia-induced ED. In Protocol-1 (P1), resveratrol was administrated to the rabbits simultaneously with CD in order to evaluate the protective effect, and for Protocol-2 (P2), resveratrol was administrated for 6 weeks after termination of CD in order to evaluate the restorative effect. Endothelium-dependent relaxations of CC were evaluated by using organ bath studies. In order to elucidate the possible molecular mechanisms, we measured endothelial NO synthase (eNOS) and phosphovasodilator-stimulated phosphoprotein (VASP) expressions and activations, NADPH oxidase, superoxide dismutase (SOD), and catalase (CAT) and glutathione peroxidase (GPx) activity in cavernosal tissues obtained at the end of the study. Resveratrol showed an improvement in the endothelium-dependent relaxation responses in vitro. We demonstrated significantly increased activatory-phosphorylation (p[S1177]-eNOS) and activated phosphovasodilator-stimulated phosphoprotein (phospho-VASP) levels, but reduced phosphorylation (p[T495]-eNOS) of eNOS and NADPH oxidase activity in the resveratrol-administered HC animals compared with hypercholesterolemic control rabbits in the P1. In the P2, resveratrol exhibited an improvement in endothelium-dependent relaxation responses and more pronounced effects on eNOS activation. Resveratrol administration, either simultaneously with HC diet

  19. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    OpenAIRE

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

    2015-01-01

    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induc...

  20. Resveratrol and Epigallocatechin-3-gallate addition to thawed boar sperm improves in vitro fertilization.

    Science.gov (United States)

    Gadani, B; Bucci, D; Spinaci, M; Tamanini, C; Galeati, G

    2017-03-01

    Thawing is one of the most delicate process after semen cryopreservation as spermatozoa pass from a dormant metabolic stage to a sudden awakening in cellular metabolism. The rapid oxygen utilization leads to an overproduction of reactive oxygen species that can damage sperm cells, thus causing a significant decrease of fertilizing potential of frozen-thawed spermatozoa. Resveratrol (Res) is a natural grape-derived phytoalexin and Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea (Camellia sinensis); both molecules are known to possess high levels of antioxidant activity. The objective of the present study was to assess the effect of different concentrations of Res (0.5, 1 or 2 mM; Experiment 1) or EGCG (25, 50 or 100 μM; Experiment 2) supplementation to thawing boar semen extender on sperm quality parameters (viability and acrosome integrity) and in vitro fertilization (IVF). Semen after thawing and dilution with three volumes of Beltsville Thawing Solution (BTS), was immediately divided in control group without antioxidants addition (CTR) and either Res or EGCG groups. Sperm viability and acrosome integrity were evaluated in CTR, Res or EGCG groups after 1 h of incubation at 37 °C. The addition of different doses of Res or EGCG to thawing extender for 1 h did not induce any effect on boar sperm viability and acrosome integrity. However, both Res and EGCG treated samples exhibited a significantly higher penetration rate compared with CTR when used for IVF. In particular the treatment with all the EGCG concentrations increased the penetration rate (P fertilization efficiency as compared to control (EGCG 25 μM: 40.3 ± 8.2 vs 26.8 ± 9.5, P fertilization. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol

    Directory of Open Access Journals (Sweden)

    Sedat Bilgiç

    2017-01-01

    Full Text Available Objective. The aim of the study was to investigate the possible protective qualities of resveratrol (RSV against the side effects of risperidone (RIS in an experimental model in rat kidneys with histologic and biochemical assessments. Materials and Methods. Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n=7 were in group 1; group 2 was given 2 mg/kg/day RIS (n=7; group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n=7; group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n=7; and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n=7. All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. Results. The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS and decreased serum creatinine (Cr, blood urea nitrogen (BUN, oxidative stress index (OSI, and total oxidant status (TOS levels significantly (p<0.05. Conclusion. This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

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

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    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

  3. Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells.

    Science.gov (United States)

    Lubbers, Justin; Lewis, Steven; Harper, Emily; Hledin, Michael P; Marquez, Gabriel A; Johnson, Alyssa E; Graves, Danelle R; Burnatowska-Hledin, Maria A

    2011-04-01

    Vasopressin-activated calcium-mobilizing (VACM-1) protein is a cul-5 gene product that forms complexes with a subclass of ubiquitin E3 ligases involved in proteasomal protein degradation. The expression of VACM-1 cDNA in the T47D breast cancer cell line inhibits growth and decreases phosphorylation of mitogen activated protein kinase. Factors that regulate expression or stability of VACM-1 protein have not been identified, however. In our search to identify drugs/substances that may control VACM-1 protein expression, we examined the effects of resveratrol (trans-3,5,4'-trihydroxystilbene), a natural component in the human diet which inhibits tumor initiation and promotion. CMV vector and VACM-1 cDNA stably transfected T47D breast cancer-derived cells were treated with resveratrol and cell growth and VACM-1 protein concentrations were measured. Since the cellular mechanism of resveratrol-dependent inhibition of cell growth also involves the regulation of estrogen receptors, the effect of 17-β-estradiol and resveratrol on ERα levels and on cell growth was examined in control and in VACM-1 cDNA transfected cells. Our results demonstrate that antiproliferative effect of resveratrol observed in the control T47D cancer cells was significantly enhanced in VACM-1 cDNA transfected T47D cells. Western blot results indicated that resveratrol increased VACM-1 protein concentration. Finally, treatment with resveratrol for 24 and 48 h attenuated 17-β-estradiol induced increase in cell growth both in control and in VACM-1 cDNA transfected cells. The effect was significantly higher in the VACM-1 cDNA transfected cells when compared to controls. These results indicate that the antiproliferative effect of resveratrol may involve induction of VACM-1/cul5.

  4. Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials.

    Science.gov (United States)

    Fogacci, Federica; Tocci, Giuliano; Presta, Vivianne; Fratter, Andrea; Borghi, Claudio; Cicero, Arrigo F G

    2018-01-23

    Results of previous clinical trials evaluating the effect of resveratrol supplementation on blood pressure (BP) are controversial. We aimed to assess the impact of resveratrol on BP through systematic review of literature and meta-analysis of available randomized, controlled clinical trials (RCTs). Literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 17th October 2017 to identify RCTs investigating the impact of resveratrol on BP. Two review authors independently extracted data on study characteristics, methods and outcomes. Overall, the impact of resveratrol on BP was reported in 17 trials. Administration of resveratrol did not significantly affect neither systolic BP [weighted mean difference (WMD): -2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I 2 =62.1%], nor diastolic BP [WMD: -0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I 2 =50.8], nor mean BP [MAP; WMD: -1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I 2 =39.5%] nor pulse pressure [PP; WMD: -0.9 95% CI:(-3.1, 1.4) mmHg; p=0.449; I 2 =19.2%]. However, significant WMDs were detected in subsets of studies categorized according to high resveratrol daily dosage (≥300 mg/day) and presence of diabetes. Meta-regression analysis revealed a positive association between systolic BP-lowering resveratrol activity (slope: 1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at baseline, while no association was detected neither between baseline BMI and MAP-lowering resveratrol activity (slope: 1.35; 95% CI: -0.22, 2.91; two-tailed p= 0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03; 95% CI: -1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated and no serious adverse events occurred among most of the eligible trials. The favourable effect of resveratrol emerging from the current meta-analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health, mostly when used in

  5. Resveratrol protects against experimental induced Reye's syndrome by prohibition of oxidative stress and restoration of complex I activity.

    Science.gov (United States)

    Abdin, Amany; Sarhan, Naglaa

    2014-09-01

    This study was designed to investigate whether resveratrol could provide protection against Reye's syndrome induced by 4-pentenoic acid in Wistar albino rats. Compared with rats with untreated Reye's syndrome, 1 h pretreatment by low dose resveratrol (10 mg/kg by oral gavage) resulted in marked amelioration in liver functions in the form of significant decrease in serum transaminases (AST, ALT) and plasma ammonia levels, shortening of prothrombin time, and increase in serum albumin levels. In addition, resveratrol prohibited oxidative stress markers, as indicated by a significant increase in GSH and decrease in MDA, with restoration of complex I activity in liver tissues. The classical histopathological presentation in Reye's syndrome of microvesicular steatosis by light microscope and mitochondria distortion by electron microscope has been improved by resveratrol pretreatment. The efficient protection by resveratrol was determined by normalization in serum levels of AST and albumin, as well as complex I activity, GSH, and MDA. In conclusion, pretreatment by resveratrol in low doses could protect against Reye's syndrome partially via prohibition of oxidative stress and restoration of complex I activity. This may provide the opportunity to reconsider aspirin therapy for infants and young children. However, the verification of such results in clinical practice remains a challenge.

  6. Danske rødvine indeholder kun lidt resveratrol

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  7. An Overview of Stress-Induced Resveratrol Synthesis in Grapes: Perspectives for Resveratrol-Enriched Grape Products

    OpenAIRE

    Mohidul Hasan; Hanhong Bae

    2017-01-01

    Resveratrol is the most important stilbene phytoalexin synthesized naturally or induced in plants, as a part of their defense mechanism. Grapes and their derivative products, including juice and wine, are the most important natural sources of resveratrol, consisting of notably higher amounts than other natural sources like peanuts. Consumption of red wine with its presence of resveratrol explained the “French Paradox”. Hence, the demand of resveratrol from grapes is increasing. Moreover, as a...

  8. Performance of Different Natural Antioxidant Compounds
in Frying Oil

    Science.gov (United States)

    Aydenız, Buket

    2016-01-01

    Summary In this study, the natural green tea extract, purified lycopene, purified resveratrol and purified γ-oryzanol were added into peanut oil and their antioxidant performances were evaluated during frying. Moreover, the sensory properties of fried dough were evaluated to determine the consumption feasibility. All natural antioxidants led to significant increase in the stability of the oil samples. The ranges of measurements in the treatment groups were as follows: free acidity 0.1–2.9 g of oleic acid per 100 g of oil, conjugated dienes 0.01–0.40 g per 100 g of oil, total polar material 8.8–73.8 g per 100 g of oil, total phenolics 0.1–4.2 mg of gallic acid equivalents per 100 g of oil, and antioxidant capacity 0.5–11.0 mM of Trolox equivalents per 100 g of oil. The fatty acid and sterol compositions indicated that antioxidant supplementation could slow the oxidative degradation of unsaturated fatty acids and reduce trans-acid formation. Frying oil enriched with purified γ-oryzanol had higher sterol levels than the other enriched oil samples. The obtained quality of oil protection was in descending order: purified γ-oryzanol, green tea extract and purified lycopene. PMID:27904389

  9. Performance of Different Natural Antioxidant Compounds in Frying Oil

    Directory of Open Access Journals (Sweden)

    Buket Aydenız

    2016-01-01

    Full Text Available In this study, the natural green tea extract, purified lycopene, purified resveratrol and purified γ-oryzanol were added into peanut oil and their antioxidant performances were evaluated during frying. Moreover, the sensory properties of fried dough were evaluated to determine the consumption feasibility. All natural antioxidants led to significant increase in the stability of the oil samples. The ranges of measurements in the treatment groups were as follows: free acidity 0.1–2.9 g of oleic acid per 100 g of oil, conjugated dienes 0.01–0.40 g per 100 g of oil, total polar material 8.8–73.8 g per 100 g of oil, total phenolics 0.1–4.2 mg of gallic acid equivalents per 100 g of oil, and antioxidant capacity 0.5–11.0 mM of Trolox equivalents per 100 g of oil. The fatty acid and sterol compositions indicated that antioxidant supplementation could slow the oxidative degradation of unsaturated fatty acids and reduce trans-acid formation. Frying oil enriched with purified γ-oryzanol had higher sterol levels than the other enriched oil samples. The obtained quality of oil protection was in descending order: purified γ-oryzanol, green tea extract and purified lycopene.

  10. Evaluation of the effects of resveratrol and bevacizumab on experimental corneal alkali burn.

    Science.gov (United States)

    Doganay, Selim; Firat, Penpe Gul; Cankaya, Cem; Kirimlioglu, Hale

    2013-03-01

    To evaluate the effects of resveratrol and bevacizumab on experimental corneal neovascularization. A corneal alkali burn was performed in 62 eyes of 31 male white Vienna rabbits. Resveratrol (group 1), dimethyl sulfoxide (group 2), bevacizumab (group 3) and 0.9% NaCl (group 4) were administered to both eyes of the rabbits by subconjunctival injection for 7 days. Corneal photos were taken at 15 days after alkali injury. Inflammatory index scores and neovascularization areas were calculated. In bevacizumab group both inflammatory index scores and the calculation of the corneal neovascularization area was significantly less than the groups. The subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit corneal alkali burn model. No effect of resveratrol to the corneal neovascularization on experimental model of the corneal alkali burn was seen at the doses of usage. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

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

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    Otis L Blanchard

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

  12. Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

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    M Andrea Markus

    Full Text Available Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.

  13. 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

  14. Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain

    Directory of Open Access Journals (Sweden)

    Maia Jr H

    2012-10-01

    Full Text Available Hugo Maia Jr,1,2 Clarice Haddad,2 Nathanael Pinheiro,3,4 Julio Casoy21Itaigara Memorial Day Hospital, 2Centro de Pesquisas e Assistência em Reprodução Humana, 3ImagePat, Pathology Laboratory, 4Department of Pathology and Forensic Medicine, Federal University of Bahia, Salvador, Bahia, BrazilBackground: The effect of resveratrol on the management of endometriosis-related pain was investigated in 12 patients who failed to obtain pain relief during use of an oral contraceptive containing drospirenone + ethinylestradiol.Methods and results: The addition of 30 mg of resveratrol to the contraceptive regimen resulted in a significant reduction in pain scores, with 82% of patients reporting complete resolution of dysmenorrhea and pelvic pain after 2 months of use. In a separate experiment, aromatase and cyclo-oxygenase-2 expression were investigated in the endometrial tissue of 42 patients submitted to laparoscopy and hysteroscopy for the management of endometriosis. Sixteen of these patients were using oral contraceptives alone prior to hospital admission, while the remaining 26 were using them in combination with resveratrol. Inhibition of both aromatase and cyclo-oxygenase-2 expression was significantly greater in the eutopic endometrium of patients using combined drospirenone + resveratrol therapy compared with the endometrium of patients using oral contraceptives alone.Conclusion: These results suggest that resveratrol potentiates the effect of oral contraceptives in the management of endometriosis-associated dysmenorrhea by further decreasing aromatase and cyclo-oxygenase-2 expression in the endometrium.Keywords: resveratrol, drospirenone, endometriosis, dysmenorrhea, cyclo-oxygenase-2

  15. Resveratrol and cancer: focus on in vivo evidence

    Science.gov (United States)

    Carter, Lindsay G; D'Orazio, John A; Pearson, Kevin J

    2014-01-01

    Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, however, comparatively fewer studies that have investigated resveratrol treatment and cancer outcomes in vivo, perhaps limited by its poor bioavailability when taken orally. Although research in cell culture has shown promising and positive effects of resveratrol, evidence from rodents and humans is inconsistent. This review highlights the in vivo effects of resveratrol treatment on breast, colorectal, liver, pancreatic, and prostate cancers. Resveratrol supplementation in animal models of cancer has shown positive, neutral as well as negative outcomes depending on resveratrol route of administration, dose, tumor model, species, and other factors. Within a specific cancer type, there is variability between studies with respect to strain, age, and sex of animal used, timing and method of resveratrol supplementation, and dose of resveratrol used to study cancer endpoints. Together, the data suggest that many factors need to be considered before resveratrol can be used for human cancer prevention or therapy. PMID:24500760

  16. Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation.

    Science.gov (United States)

    Shabani Nashtaei, M; Amidi, F; Sedighi Gilani, M A; Aleyasin, A; Bakhshalizadeh, Sh; Naji, M; Nekoonam, S

    2017-03-01

    Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5' AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μm for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and

  17. Dominant Carbons in trans- and cis-Resveratrol Isomerization.

    Science.gov (United States)

    Wang, Feng; Chatterjee, Subhojyoti

    2017-05-11

    A comprehensive analysis for isomerization of geometric isomers in the case of resveratrol (R) has been presented. As an important red wine molecule, only one geometric isomer of resveratrol, i.e., trans-R rather than cis-R, is primarily associated with health benefit. In the present study, density function theory (DFT) provides accurate descriptions of isomerization of resveratrol. The nearly planar trans-R forms a relatively rigid and less flexible conjugate network, but the nonplanar cis-R favors a more flexible structure with steric through space interaction. The calculated carbon nuclear magnetic resonance (NMR) chemical shift indicates that all carbons are different in the isomers; it further reveals that four carbon sites, i.e., C (6) , C (8) ═C (9) , and C (11) , have a significant response to the geometric isomerization. Here C (6) is related to the steric effect in cis-R, whereas C (11) may indicate the isomerization proton transfer on C (9) linking with the resorcinol ring. The excess orbital energy spectrum (EOES) confirms the NMR "bridge of interest" carbons and reveals that five valence orbitals of 34a, 35a, 46a, 55a, and 60a respond to the isomerization most significantly. The highest occupied molecular orbital (HOMO), 60a, of the isomer pair is further studied using dual space analysis (DSA) for its orbital momentum distributions, which exhibit p-electron dominance for trans-R but hybridized sp-electron dominance for cis-R. Finally, energy decomposition analysis (EDA) highlights that trans-R is preferred over cis-R by -4.35 kcal·mol -1 , due to small electrostatic energy enhancement of the attractive orbital energy with respect to the Pauli repulsive energy.

  18. Pharmacological stimulation of nuclear factor (erythroid-derived 2)-like 2 translation activates antioxidant responses.

    Science.gov (United States)

    Perez-Leal, Oscar; Barrero, Carlos Alberto; Merali, Salim

    2017-08-25

    Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of the antioxidant response, and its function is tightly regulated at the transcriptional, translational, and post-translational levels. It is well-known that Nrf2 is regulated at the protein level by proteasomal degradation via Kelch-like ECH-associated protein 1 (Keap1), but how Nrf2 is regulated at the translational level is less clear. Here, we show that pharmacological stimulation increases Nrf2 levels by overcoming basal translational repression. We developed a novel reporter assay that enabled identification of natural compounds that induce Nrf2 translation by a mechanism independent of Keap1-mediated degradation. Apigenin, resveratrol, and piceatannol all induced Nrf2 translation. More importantly, the pharmacologically induced Nrf2 overcomes Keap1 regulation, translocates to the nucleus, and activates the antioxidant response. We conclude that translational regulation controls physiological levels of Nrf2, and this can be modulated by apigenin, resveratrol, and piceatannol. Also, targeting this mechanism with novel compounds could provide new insights into prevention and treatment of multiple diseases in which oxidative stress plays a significant role. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2011-12-01

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

  20. 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

    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...

  1. Metabolic Engineering of Yeast and Plants for the Production of the Biologically Active Hydroxystilbene, Resveratrol

    Science.gov (United States)

    Jeandet, Philippe; Delaunois, Bertrand; Aziz, Aziz; Donnez, David; Vasserot, Yann; Cordelier, Sylvain; Courot, Eric

    2012-01-01

    Resveratrol, a stilbenic compound deriving from the phenyalanine/polymalonate route, being stilbene synthase the last and key enzyme of this pathway, recently has become the focus of a number of studies in medicine and plant physiology. Increased demand for this molecule for nutraceutical, cosmetic and possibly pharmaceutic uses, makes its production a necessity. In this context, the use of biotechnology through recombinant microorganisms and plants is particularly promising. Interesting results can indeed arise from the potential of genetically modified microorganisms as an alternative mechanism for producing resveratrol. Strategies used to tailoring yeast as they do not possess the genes that encode for the resveratrol pathway, will be described. On the other hand, most interest has centered in recent years, on STS gene transfer experiments from various origins to the genome of numerous plants. This work also presents a comprehensive review on plant molecular engineering with the STS gene, resulting in disease resistance against microorganisms and the enhancement of the antioxidant activities of several fruits in transgenic lines. PMID:22654481

  2. Effects of resveratrol and other wine polyphenols on the proliferation, apoptosis and androgen receptor expression in LNCaP cells.

    Science.gov (United States)

    Ferruelo, A; Romero, I; Cabrera, P M; Arance, I; Andrés, G; Angulo, J C

    2014-01-01

    To address the effect of resveratrol and other red wine polyphenols on cell proliferation, apoptosis and androgen receptor (AR) expression in human prostate cancer LNCaP cells. LNCaP cells (5 × 102) were cultured in microtiter plate modules and treated with gallic acid, tannic acid and quercetin (1, 5 and 10 μM), rutin and morin (25, 50 and 75 μM) and resveratrol (5, 10 and 25 μM). To address the extent of proliferation at 24, 48, 72 and 96 hours, a colorimetric immunoassay method was used. An activity caspase 3/7 detection assay was used to disclose apoptosis at 24, 48 and 72 hours. AR mARN levels were determined by real time RT-PCR. All polyphenols studied significantly inhibited (P<.05) cell proliferation compared to control. However, there were moderate differences between them. Resveratrol was the strongest inhibitor at different times and doses. Also, caspase-3 and caspase-7 activity was significantly higher (P<.05) than control in the presence of all the compounds, but the earlier response was achieved by resveratrol. Resveratrol, quercetin and morin were the only nutrients that significantly inhibited AR mRNA expression. Again resveratrol produced the highest inhibition (90-250 times less than control), followed by morin (67-100 times) and quercetin (55-91 times). All polyphenols studied showed important antiproliferative effects and induced apoptosis when added to LNCaP cells culture. We confirm that resveratrol, morin and quercetin may achieve such effect through reduced expression of AR. The synergistic effects of these compounds and their potential to prevent progression of hormone-dependent prostate cancer merit further study. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

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

  4. Protective effects of Resveratrol in an experimental model of abdominal aortic aneurysm induction

    Directory of Open Access Journals (Sweden)

    D. Palmieri

    2011-01-01

    Full Text Available Resveratrol (Rsv is a natural antioxidant polyphenol with vasoprotective properties. We evaluated whether Rsv affects the inflammatory response in an experimental model of elastase-induced abdominal aortic aneurysm. Thirty male rats were subjected to aneurysm induction and treated or not with Rsv. Circulating levels of CD62L-monocyte subset, monocyte CD I 43 surface expression, MMP-9 plasma activity and TNFα serum levels were lower in Rsv-treated rats. In conclusion. Rsv acts as an anti-inflammatory compound and could be of great revelance to improve the immune response in AAA patients.

  5. Commentary on resveratrol and hormesis: resveratrol--a hormetic marvel in waiting?

    Science.gov (United States)

    Marques, Francine Z; Morris, Brian J

    2010-12-01

    Hormesis is a phenomenon in which adaptive responses to low doses of otherwise-harmful factors (also called mild stressors) make cells and organisms more robust. In their review, Calabrese et al. provide evidence for resveratrol acting hormetically in different types of human cell lines. The effects of resveratrol represent a 'two-edged sword' in that it has contrasting effects at low and high doses in healthy and cancerogenous cells. What demarcates a low and a high dose needs to be clarified. Concentrations tested in cell cultures, moreover, may not be relevant to whole organisms. And data from animal models need not apply to humans. Co-morbidities should also be considered. More research is needed to understand the action of resveratrol on all cell types and conditions, and the optimum therapeutic concentration that applies to each of these. Future research needs to determine the dynamics of the effects of resveratrol in different subcellular compartments and the interactions of these. In addition, the interactions between resveratrol, environmental factors, other compounds and medications, diseases and the genetic background of the individual will need to be appreciated in order to gain a complete understanding of the hormetic response of resveratrol.

  6. Resveratrol suppresses ethanol stress in winery and bottom brewery yeast by affecting superoxide dismutase, lipid peroxidation and fatty acid profile.

    Science.gov (United States)

    Gharwalova, Lucia; Sigler, Karel; Dolezalova, Jana; Masak, Jan; Rezanka, Tomas; Kolouchova, Irena

    2017-11-03

    Mid-exponential cultures of two traditional biotechnological yeast species, winery Saccharomyces cerevisiae and the less ethanol tolerant bottom-fermenting brewery Saccharomyces pastorianus, were exposed to different concentrations of added ethanol (3, 5 and 8%) The degree of ethanol-induced cell stress was assessed by measuring the cellular activity of superoxide dismutase (SOD), level of lipid peroxidation products, changes in cell lipid content and fatty acid profile. The resveratrol as an antioxidant was found to decrease the ethanol-induced rise of SOD activity and suppress the ethanol-induced decrease in cell lipids. A lower resveratrol concentration (0.5 mg/l) even reduced the extent of lipid peroxidation in cells. Resveratrol also alleviated ethanol-induced changes in cell lipid composition in both species by strongly enhancing the proportion of saturated fatty acids and contributing thereby to membrane stabilization. Lower resveratrol concentrations could thus diminish the negative effects of ethanol stress on yeast cells and improve their physiological state. These effects may be utilized to enhance yeast vitality in high-ethanol-producing fermentations or to increase the number of yeast generations in brewery.

  7. 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

  8. Growth-rate dependency of de novo resveratrol production in chemostat cultures of an engineered Saccharomyces cerevisiae strain.

    Science.gov (United States)

    Vos, Tim; de la Torre Cortés, Pilar; van Gulik, Walter M; Pronk, Jack T; Daran-Lapujade, Pascale

    2015-09-14

    Saccharomyces cerevisiae has become a popular host for production of non-native compounds. The metabolic pathways involved generally require a net input of energy. To maximize the ATP yield on sugar in S. cerevisiae, industrial cultivation is typically performed in aerobic, sugar-limited fed-batch reactors which, due to constraints in oxygen transfer and cooling capacities, have to be operated at low specific growth rates. Because intracellular levels of key metabolites are growth-rate dependent, slow growth can significantly affect biomass-specific productivity. Using an engineered Saccharomyces cerevisiae strain expressing a heterologous pathway for resveratrol production as a model energy-requiring product, the impact of specific growth rate on yeast physiology and productivity was investigated in aerobic, glucose-limited chemostat cultures. Stoichiometric analysis revealed that de novo resveratrol production from glucose requires 13 moles of ATP per mole of produced resveratrol. The biomass-specific production rate of resveratrol showed a strong positive correlation with the specific growth rate. At low growth rates a substantial fraction of the carbon source was invested in cellular maintenance-energy requirements (e.g. 27 % at 0.03 h(-1)). This distribution of resources was unaffected by resveratrol production. Formation of the by-products coumaric, phloretic and cinnamic acid had no detectable effect on maintenance energy requirement and yeast physiology in chemostat. Expression of the heterologous pathway led to marked differences in transcript levels in the resveratrol-producing strain, including increased expression levels of genes involved in pathways for precursor supply (e.g. ARO7 and ARO9 involved in phenylalanine biosynthesis). The observed strong differential expression of many glucose-responsive genes in the resveratrol producer as compared to a congenic reference strain could be explained from higher residual glucose concentrations and higher

  9. Multiple anti-inflammatory pathways triggered by resveratrol lead to amelioration of staphylococcal enterotoxin B-induced lung injury.

    Science.gov (United States)

    Rieder, Sadiye Amcaoglu; Nagarkatti, Prakash; Nagarkatti, Mitzi

    2012-11-01

    Inhalation of the superantigen,staphylococcal enterotoxin B (SEB), leads to the activation of the host T and invariant natural killer (iNK) T cells, thereby resulting in acute lung inflammation and respiratory failure but the underlying mechanism(s) of disease remain elusive, with limited treatment options. In this study, we investigated the therapeutic effectiveness of resveratrol, a plant polyphenol, during SEB-induced lung inflammation. C57BL/6 mice were exposed to SEB (50 µg·per mouse), administered intranasally, and were treated with resveratrol (100 mg·kg(-1)) before or after SEB exposure. Lung injury was studied by measuring vascular permeability, histopathological examination, nature of infiltrating cells, inflammatory cytokine induction in the bronchoalveolar fluid (BALF), apoptosis in SEB-activated T cells and regulation of SIRT1 and NF-κB signalling pathways. Pretreatment and post-treatment with resveratrol significantly reduced SEB-induced pulmonary vascular permeability, and inflammation. Resveratrol significantly reduced lung infiltrating cells and attenuated the cytokine storm in SEB-exposed mice, which correlated with increased caspase-8-dependent apoptosis in SEB-activated T cells. Resveratrol treatment also markedly up-regulated Cd11b+ and Gr1+ myeloid-derived suppressor cells (MDSCs) that inhibited SEB-mediated T cell activation in vitro. In addition, resveratrol treatment was accompanied by up-regulation of SIRT1 and down-regulation of NF-κB in the inflammatory cells of the lungs. The current study demonstrates that resveratrol may constitute a novel therapeutic modality to prevent and treat SEB-induced lung inflammation inasmuch because it acts through several pathways to reduce pulmonary inflammation. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  10. Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

    Science.gov (United States)

    Kuroyanagi, Gen; Otsuka, Takanobu; Yamamoto, Naohiro; Matsushima-Nishiwaki, Rie; Nakakami, Akira; Mizutani, Jun; Kozawa, Osamu; Tokuda, Haruhiko

    2014-01-01

    It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation. PMID:25290095

  11. Effect of resveratrol on lipid profile: An updated systematic review and meta-analysis on randomized clinical trials.

    Science.gov (United States)

    Haghighatdoost, Fahimeh; Hariri, Mitra

    2018-03-01

    Despite the notion that resveratrol can significantly reduce plasma lipids, the result of randomized clinical trials (RCTs) on resveratrol effect and the serum lipid profile are contradictory. Our objective was to conduct a systematic review and meta-analysis on randomized clinical trials (RCTs) and assess the effect of resveratrol on lipids. ISI web of science, Ovid, PubMed/Medline, SCOPUS, and Google Scholar data bases were searched up to Jun 2017. RCTs that assessed resveratrol effects on lipid profile among adult participants were chosen. Treatment effects were considered as weighted mean difference (WMD) and the corresponding standard error (SE) in concentrations of serum lipids. To estimate the overall summary effect, we used random-effects model. The protocol was registered with PROSPERO (No. CRD42017072365). This meta-analysis was performed on twenty-one trials. Our results indicated that resveratrol can't significantly change total cholesterol (TC) (WMD = -0.08 mmol/l, 95% CI: -0.23, 0.08; P = .349, I 2  = 87.8%), low-density lipoprotein (LDL-C) (WMD: -0.04 mmol/l, 95% CI: -0.21, 0.12; P = .620, I 2  = 93.4%), and high density lipoprotein (HDL-C) (WMD: -0.01 mmol/l, 95% CI: -0.04, 0.02; P = .269, I 2  = 88.6%). Its effect on triacylglycerol (TG) (WMD: 0.58 mmol/l, 95% CI: 0.34, 0.82; P resveratrol dosage, and intervention duration could not change the results. We conclude that resveratrol does not change lipid profile concentration. Confirmation of this conclusion will require more studies exclusively on dyslipidemic patients in which the intake of lipid lowering agents is among the exclusion criteria. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Insight in the phenolic composition and antioxidative properties of Vitis vinifera leaves extracts

    Directory of Open Access Journals (Sweden)

    Ivana Generalić

    2009-01-01

    , apigenin, myricetin, quercetin, quercetin-4'-glucoside, rutin, and stilbenes (trans-resveratrol and resveratrol derivatives was confirmed in both extracts. According to the results achieved, vine leaf extracts can be considered rich natural source of polyphenols with significant antioxidant properties.

  13. Red Wine, Resveratrol and Atrial Fibrillation.

    Science.gov (United States)

    Stephan, Laura Siga; Almeida, Eduardo Dytz; Markoski, Melissa Medeiros; Garavaglia, Juliano; Marcadenti, Aline

    2017-10-30

    Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF.

  14. Resveratrol derivatives: a patent review (2009 - 2012).

    Science.gov (United States)

    Pezzuto, John M; Kondratyuk, Tamara P; Ogas, Talysa

    2013-12-01

    There is currently a wealth of information on the effects of resveratrol and its derivatives in therapeutic, cosmetic and nutraceutical patent applications. Structure-activity studies of the resveratrol scaffold provide a foundation for the development of new analogs with potent activity or other beneficial properties. Ongoing research has yielded promising results and potential use in the treatment of various diseases. This review provides analysis of patents published from January 2009 to April 2013. There is a focus on different approaches for the production of resveratrol derivatives, combinations of new derivatives with old drugs, and applications in therapeutic areas, nutraceutical compositions and cosmetics. The ability of resveratrol to interact with a disparate array of subcellular targets is uncanny. Nonetheless, even though limited or no toxicity is apparent, the molecule is not a panacea due to lack of potency and issues with bioavailability. Thus, as witnessed by a number of patents, a large assortment of derivatives have been synthesized under the guise of having superior characteristics for treating or preventing various diseases or for use as neutraceutics and cosmetics. Some of these suppositions are probably correct, but evidence-based applications are essentially nil due to a lack of commitment in terms of investing the resources necessary for the conduct of obligatory clinical trials. Current usage is largely based on anecdotes and publicity. Hopefully, at some point in time, it will be possible to follow a standard protocol with a predicable outcome.

  15. Red Wine, Resveratrol and Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Laura Siga Stephan

    2017-10-01

    Full Text Available Atrial fibrillation (AF is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF.

  16. Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats.

    Science.gov (United States)

    Abdel-Wahab, Basel A; Abdel-Wahab, Mahmoud M

    2016-05-15

    Long-term intermittent hypoxia (IH) is a characteristic hallmark of obstructive sleep apnea (OSA) and causes most of the neurological aspects of OSA, such as spatial memory and learning deficits. These deficits are accompanied by an increase in oxidative stress and inflammation in brain areas involved in cognition, such as the hippocampus, particularly in children. Resveratrol is a natural polyphenolic compound with potent antioxidant, anti-inflammatory and neuroprotective properties. The aim of this work is to study the possible protective effect of resveratrol against IH-induced neurobehavioral deficits and to investigate the possible mechanism of this protective effect in the young rat model of OSA. The effect of resveratrol (5 and 10mg/kg, orally) on anxiety, spatial memory and learning deficits in young rats exposed to IH for 6 weeks and the corresponding biochemical changes were studied. Resveratrol attenuated IH-induced anxiety and spatial memory deficits, as indicated by the elevated plus maze and Morris water maze tests, respectively, in a dose-dependent manner. In addition, resveratrol antagonized IH-induced increases in hippocampal glutamate, TBARS and 8-OHdG levels and p47Phox expression and decreases in GSH levels and GSH-Px activity in the hippocampus of IH-exposed young rats. Resveratrol ameliorates IH-induced anxiety and spatial learning deficits through multiple beneficial effects on hippocampal oxidative pathways that involve decreased expression of the p47Phox subunit of NADPH oxidase. Hence, the potential therapeutic role of resveratrol in OSA may be utilized in the near future and deserves further exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 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

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

    Science.gov (United States)

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

    2016-01-01

    Barringtonia racemosa is a medicinal plant belonging to the Lecythidaceae family. The water extract of B. racemosa leaf (BLE) has been shown to be rich in polyphenols. Despite the diverse medicinal properties of B. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking. In this study, the effect of the antioxidant-rich BLE on gene expression in HepG2 cells was investigated using microarray analysis in order to shed more light on the molecular mechanism associated with the medicinal properties of the plant. Microarray analysis showed that a total of 138 genes were significantly altered in response to BLE treatment (p Degradation III followed by VDR/RXR activation, TR/RXR activation, PXR/RXR activation and gluconeogenesis. The expression of genes that encode for enzymes involved in methylglyoxal degradation (ADH4, AKR1B10 and AKR1C2) and glycolytic process (ENO3, ALDOC and SLC2A1) was significantly regulated. Owing to the Warburg effect, aerobic glycolysis in cancer cells may increase the level of methylglyoxal, a cytotoxic compound. BLE has the potential to be developed into a novel chemopreventive agent provided that the cytotoxic effects related to methylglyoxal accumulation are minimized in normal cells that rely on aerobic glycolysis for energy supply.

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

    Directory of Open Access Journals (Sweden)

    Kin Weng Kong

    2016-08-01

    Full Text Available Background Barringtonia racemosa is a medicinal plant belonging to the Lecythidaceae family. The water extract of B. racemosa leaf (BLE has been shown to be rich in polyphenols. Despite the diverse medicinal properties of B. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking. Methods In this study, the effect of the antioxidant-rich BLE on gene expression in HepG2 cells was investigated using microarray analysis in order to shed more light on the molecular mechanism associated with the medicinal properties of the plant. Results Microarray analysis showed that a total of 138 genes were significantly altered in response to BLE treatment (p < 0.05 with a fold change difference of at least 1.5. SERPINE1 was the most significantly up-regulated gene at 2.8-fold while HAMP was the most significantly down-regulated gene at 6.5-fold. Ingenuity Pathways Analysis (IPA revealed that “Cancer, cell death and survival, cellular movement” was the top network affected by the BLE with a score of 44. The top five canonical pathways associated with BLE were Methylglyoxal Degradation III followed by VDR/RXR activation, TR/RXR activation, PXR/RXR activation and gluconeogenesis. The expression of genes that encode for enzymes involved in methylglyoxal degradation (ADH4, AKR1B10 and AKR1C2 and glycolytic process (ENO3, ALDOC and SLC2A1 was significantly regulated. Owing to the Warburg effect, aerobic glycolysis in cancer cells may increase the level of methylglyoxal, a cytotoxic compound. Conclusions BLE has the potential to be developed into a novel chemopreventive agent provided that the cytotoxic effects related to methylglyoxal accumulation are minimized in normal cells that rely on aerobic glycolysis for energy supply.

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

    Science.gov (United States)

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

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Resveratrol treatment as an adjunct to pharmacological management in type 2 diabetes mellitus--systematic review and meta-analysis.

    Science.gov (United States)

    Hausenblas, Heather A; Schoulda, Jennifer A; Smoliga, James M

    2015-01-01

    The red wine polyphenol, resveratrol, is highly effective in treating type 2 diabetes mellitus (T2DM) in animal models, but there is no consensus regarding its efficacy in humans. We conducted a systematic review, which included searches in nine scholarly databases and six clinical trial registries, and identified randomized controlled clinical trials whereby resveratrol was used as an adjunct to pharmaceutical interventions in T2DM. Meta-analysis on clinical parameters was performed for available data. Of 764 articles originally identified, data from six unique datasets, examining a total of 196 T2DM patients (104 resveratrol, 92 control/placebo) ultimately met inclusion criteria. Statistically significant (p fasting glucose, homeostatic model assessment of insulin resistance, diastolic blood pressure, insulin, triglycerides, LDL, or HDL cholesterol. No major adverse events were reported and side effects of resveratrol were not different than placebo/control. Though limitations in sample size and treatment duration preclude definitive changes in clinical practice, significant improvements in multiple cardiometabolic biomarkers and an excellent safety profile support resveratrol as a leading candidate as an adjunct to pharmacological management of T2DM. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Resveratrol supplementation and plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mohammadi-Sartang, Mohsen; Mazloom, Zohreh; Sohrabi, Zahra; Sherafatmanesh, Saeed; Barati-Boldaji, Reza

    2017-03-01

    The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent. Our objective was to elucidate the role of resveratrol supplementation on adipokines through a systematic review and a meta-analysis of available randomized placebo-controlled trials (RCTs). 1 The search included PubMed-MEDLINE, SCOPUS and ISI web of sciences database till up to 6th November 2016. Weight mean differences (WMD) 2 were calculated for net changes in adipokines using fixed-effects or random-effects models; meta-regression analysis and publication bias were conducted in accordance with standard methods. Nine RCTs with 11 treatment arms were eligible for inclusion in this systematic review and meta-analysis. Meta-analysis of data from 10 treatment arms showed a significant change in plasma adiponectin concentrations following resveratrol supplementation (WMD: 1.10μg/ml, 95%CI: 0.88, 1.33, presveratrol supplementation (WMD: 3.77ng/ml, 95% CI: -2.28, 9.83, p=0.222; Q=8.00, I 2 =50.01%). Resveratrol significantly improves adiponectin but does not affect leptin concentrations. Additional studies are required to further evaluate the potential benefits of resveratrol on adipokines in humans. Copyright © 2017. Published by Elsevier Ltd.

  3. 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.

  4. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    OpenAIRE

    Audrey E. McCalley; Simon Kaja; Andrew J. Payne; Peter Koulen

    2014-01-01

    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 ...

  5. Biological Mechanisms by Which Antiproliferative Actions of Resveratrol Are Minimized.

    Science.gov (United States)

    Ho, Yih; Lin, Yu-Syuan; Liu, Hsuan-Liang; Shih, Ya-Jung; Lin, Shin-Ying; Shih, Ai; Chin, Yu-Tang; Chen, Yi-Ru; Lin, Hung-Yun; Davis, Paul J

    2017-09-21

    Preclinical and clinical studies have offered evidence for protective effects of various polyphenol-rich foods against cardiovascular diseases, neurodegenerative diseases, and cancers. Resveratrol is among the most widely studied polyphenols. However, the preventive and treatment effectiveness of resveratrol in cancer remain controversial because of certain limitations in existing studies. For example, studies of the activity of resveratrol against cancer cell lines in vitro have often been conducted at concentrations in the low μM to mM range, whereas dietary resveratrol or resveratrol-containing wine rarely achieve nM concentrations in the clinic. While the mechanisms underlying the failure of resveratrol to inhibit cancer growth in the intact organism are not fully understood, the interference by thyroid hormones with the anticancer activity of resveratrol have been well documented in both in vitro and xenograft studies. Thus, endogenous thyroid hormones may explain the failure of anticancer actions of resveratrol in intact animals, or in the clinic. In this review, mechanisms involved in resveratrol-induced antiproliferation and effects of thyroid hormones on these mechanisms are discussed.

  6. Biological Mechanisms by Which Antiproliferative Actions of Resveratrol Are Minimized

    Directory of Open Access Journals (Sweden)

    Yih Ho

    2017-09-01

    Full Text Available Preclinical and clinical studies have offered evidence for protective effects of various polyphenol-rich foods against cardiovascular diseases, neurodegenerative diseases, and cancers. Resveratrol is among the most widely studied polyphenols. However, the preventive and treatment effectiveness of resveratrol in cancer remain controversial because of certain limitations in existing studies. For example, studies of the activity of resveratrol against cancer cell lines in vitro have often been conducted at concentrations in the low μM to mM range, whereas dietary resveratrol or resveratrol-containing wine rarely achieve nM concentrations in the clinic. While the mechanisms underlying the failure of resveratrol to inhibit cancer growth in the intact organism are not fully understood, the interference by thyroid hormones with the anticancer activity of resveratrol have been well documented in both in vitro and xenograft studies. Thus, endogenous thyroid hormones may explain the failure of anticancer actions of resveratrol in intact animals, or in the clinic. In this review, mechanisms involved in resveratrol-induced antiproliferation and effects of thyroid hormones on these mechanisms are discussed.

  7. 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

  8. Resveratrol suppresses prostaglandin F(2α)-induced osteoprotegerin synthesis in osteoblasts: inhibition of the MAP kinase signaling.

    Science.gov (United States)

    Kuroyanagi, Gen; Tokuda, Haruhiko; Matsushima-Nishiwaki, Rie; Kondo, Akira; Mizutani, Jun; Kozawa, Osamu; Otsuka, Takanobu

    2014-01-15

    Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses various beneficial properties for human health. In the present study, we investigated the mechanism underlying the effects of prostaglandin F2α (PGF2α) on osteoprotegerin (OPG) synthesis and of resveratrol on the OPG synthesis in osteoblast-like MC3T3-E1 cells. PGF2α stimulated both the release of the OPG protein and the expression of OPG mRNA. Treatment with PD98059, SB203580 and SP600125, specific inhibitors of MEK1/2, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) all suppressed the OPG release induced by PGF2α. Resveratrol also significantly reduced the PGF2α-stimulated OPG release and the mRNA levels of OPG. Similarly, treatment with SRT1720, an activator of SIRT1, also suppressed the PGF2α-stimulated OPG release. Resveratrol and SRT1720 both attenuated the phosphorylation of p44/p42 MAP kinase, MEK1/2, Raf-1, p38 MAP kinase and SAPK/JNK induced by PGF2α. These findings strongly suggest that resveratrol suppresses PGF2α-stimulated OPG synthesis by inhibiting the MAP kinase pathways in osteoblasts, and that the effect is mediated via SIRT1 activation. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Heiduschka, G.; Lill, C.; Brunner, M.; Thurnher, D.; Seemann, R.; Schmid, R.; Houben, R.; Bigenzahn, J.

    2014-01-01

    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.) [de

  10. Synergistic Association of Valproate and Resveratrol Reduces Brain Injury in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Lara Faggi

    2018-01-01

    Full Text Available Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275, respectively, an activator of the AMP-activated kinase (AMPK-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs, synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker. In cortical neurons previously exposed to oxygen glucose deprivation (OGD, valproate elicited neuroprotection at 100 nmol/mL concentration when used alone and at 1 nmol/mL concentration when associated with resveratrol (3 nmol/mL. Resveratrol and valproate restored the acetylation of histone H3 (K9/18, and they reduced the RelA(K310 acetylation and the Bim level in neurons exposed to OGD. Chromatin immunoprecipitation analysis showed that the synergistic drug association impaired the RelA binding to the Bim promoter, as well as the promoter-specific H3 (K9/18 acetylation. In mice subjected to 60 min of middle cerebral artery occlusion (MCAO, the association of resveratrol 680 µg/kg and valproate 200 µg/kg significantly reduced the infarct volume as well as the neurological deficits. The present study suggests that valproate and resveratrol may represent a promising ready-to-use strategy to treat post-ischemic brain damage.

  11. In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery.

    Science.gov (United States)

    Jose, S; Anju, S S; Cinu, T A; Aleykutty, N A; Thomas, S; Souto, E B

    2014-10-20

    Resveratrol is a potent anticancer. However, because of its low half-life (particle size and zeta potential of the optimized formulation (drug-lipid ratio of 1:10) were 248.30 ± 3.80nm and -25.49 ± 0.49mV, respectively. The particle size and the encapsulation efficiency (EE) increased when varying the drug-lipid ratio from 1:5 to 1:15. Scanning electron microscopic (SEM) analysis showed that SLN were spherical in shape and had a smooth surface. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses revealed that the matrix of drug-loaded SLN was in disordered crystalline phase. The in vitro release study in phosphate buffer pH 7.4 followed a sustained release pattern. The drug release data was found to fit best into Higuchi kinetic model suggesting the diffusion controlled mechanism of drug release. The cytotoxicity assay (MAT) showed that SLN were equally effective (P<0.5) as free resveratrol, as an anti-tumor agent. The in vivo biodistribution study using Wistar rats demonstrated that SLN could significantly (P<0.001) increase the brain concentration of resveratrol (17.28 ± 0.6344 μg/g) as compared to free resveratrol (3.45 ± 0.3961 μg/g). The results showed that our resveratrol-loaded SLN serve as promising therapeutic systems to treat neoplastic diseases located in the brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. An Overview of Stress-Induced Resveratrol Synthesis in Grapes: Perspectives for Resveratrol-Enriched Grape Products.

    Science.gov (United States)

    Hasan, Mohidul; Bae, Hanhong

    2017-02-14

    Resveratrol is the most important stilbene phytoalexin synthesized naturally or induced in plants, as a part of their defense mechanism. Grapes and their derivative products, including juice and wine, are the most important natural sources of resveratrol, consisting of notably higher amounts than other natural sources like peanuts. Consumption of red wine with its presence of resveratrol explained the "French Paradox". Hence, the demand of resveratrol from grapes is increasing. Moreover, as a natural source of resveratrol, grapes became very important in the nutraceutical industry for their benefits to human health. The accumulation of resveratrol in grape skin, juice, and wine has been found to be induced by the external stimuli: microbial infection, ultrasonication (US) treatment, light-emitting diode (LED), ultra violet (UV) irradiation, elicitors or signaling compounds, macronutrients, and fungicides. Phenylalanine ammonia lyase, cinnamate-4-hydroxylase, coumaroyl-CoA ligase, and stilbene synthase play a key role in the synthesis of resveratrol. The up-regulation of those genes have the positive relationship with the elicited accumulation of resveratrol. In this review, we encapsulate the effect of different external stimuli (biotic and abiotic stresses or signaling compounds) in order to obtain the maximum accumulation of resveratrol in grape skin, leaves, juice, wine, and cell cultures.

  13. An Overview of Stress-Induced Resveratrol Synthesis in Grapes: Perspectives for Resveratrol-Enriched Grape Products

    Directory of Open Access Journals (Sweden)

    Mohidul Hasan

    2017-02-01

    Full Text Available Resveratrol is the most important stilbene phytoalexin synthesized naturally or induced in plants, as a part of their defense mechanism. Grapes and their derivative products, including juice and wine, are the most important natural sources of resveratrol, consisting of notably higher amounts than other natural sources like peanuts. Consumption of red wine with its presence of resveratrol explained the “French Paradox”. Hence, the demand of resveratrol from grapes is increasing. Moreover, as a natural source of resveratrol, grapes became very important in the nutraceutical industry for their benefits to human health. The accumulation of resveratrol in grape skin, juice, and wine has been found to be induced by the external stimuli: microbial infection, ultrasonication (US treatment, light-emitting diode (LED, ultra violet (UV irradiation, elicitors or signaling compounds, macronutrients, and fungicides. Phenylalanine ammonia lyase, cinnamate-4-hydroxylase, coumaroyl-CoA ligase, and stilbene synthase play a key role in the synthesis of resveratrol. The up-regulation of those genes have the positive relationship with the elicited accumulation of resveratrol. In this review, we encapsulate the effect of different external stimuli (biotic and abiotic stresses or signaling compounds in order to obtain the maximum accumulation of resveratrol in grape skin, leaves, juice, wine, and cell cultures.

  14. Resveratrol induces pro-oxidant effects and time-dependent resistance to cytotoxicity in activated hepatic stellate cells.

    Science.gov (United States)

    Martins, Leo A Meira; Coelho, Bárbara P; Behr, Guilherme; Pettenuzzo, Letícia F; Souza, Izabel C C; Moreira, José Cláudio F; Borojevic, Radovan; Gottfried, Carmem; Guma, Fátima Costa Rodrigues

    2014-03-01

    Resveratrol (RSV) is known for its antioxidant properties; however, this compound has been proposed to have cytotoxic and pro-oxidant effects depending on its concentration and time of exposure. We previously reported the cell cycle arrest effect of low doses of RSV in GRX cells, an activated hepatic stellate cell model. Here, we evaluated the effects of RSV treatment (0.1-50 μM) for 24 and 120 h on GRX viability and oxidative status. Only treatment with 50 μM of RSV reduced the amount of live cells. However, even low doses of RSV induced an increased reactive species production at both treatment times. While being diminished within 24 h, RSV induced an increase in the SOD activity in 120 h. The cellular damage was substantially increased at 24 h in the 50 μM RSV-treated group, as indicated by the high lipoperoxidation, which may be related to the significant cell death and low proliferation. Paradoxically, this cellular damage and lipoperoxidation were considerably reduced in this group after 120 h of treatment while the surviving cells proliferated. In conclusion, RSV induced a dose-dependent pro-oxidant effect in GRX cells. The highest RSV dose induced oxidative-related damage, drastically reducing cell viability; but this cytotoxicity seems to be attenuated during 120 h of treatment.

  15. 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.

  16. Resveratrol cocrystals with enhanced solubility and tabletability.

    Science.gov (United States)

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

    2016-07-25

    Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Morita Yoshihiro

    2012-02-01

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

  18. Red Wine, Resveratrol and Atrial Fibrillation

    OpenAIRE

    Stephan, Laura Siga; Almeida, Eduardo Dytz; Markoski, Melissa Medeiros; Garavaglia, Juliano; Marcadenti, Aline

    2017-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as a...

  19. Resveratrol: A novel type of topoisomerase II inhibitor.

    Science.gov (United States)

    Lee, Joyce H; Wendorff, Timothy J; Berger, James M

    2017-12-22

    Resveratrol, a polyphenol found in various plant sources, has gained attention as a possible agent responsible for the purported health benefits of certain foods, such as red wine. Despite annual multi-million dollar market sales as a nutriceutical, there is little consensus about the physiological roles of resveratrol. One suggested molecular target of resveratrol is eukaryotic topoisomerase II (topo II), an enzyme essential for chromosome segregation and DNA supercoiling homeostasis. Interestingly, resveratrol is chemically similar to ICRF-187, a clinically approved chemotherapeutic that stabilizes an ATP-dependent dimerization interface in topo II to block enzyme activity. Based on this similarity, we hypothesized that resveratrol may antagonize topo II by a similar mechanism. Using a variety of biochemical assays, we find that resveratrol indeed acts through the ICRF-187 binding locus, but that it inhibits topo II by preventing ATPase domain dimerization rather than stabilizing it. This work presents the first comprehensive analysis of the biochemical effects of both ICRF-187 and resveratrol on the human isoforms of topo II, and reveals a new mode for the allosteric regulation of topo II through modulation of ATPase status. Natural polyphenols related to resveratrol that have been shown to impact topo II function may operate in a similar manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  1. Resveratrol production in hairy root culture of peanut, Arachis ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-10-20

    Oct 20, 2008 ... hypogaea L.) hairy roots and also showed varying effects on the growth and resveratrol production in hairy root cultures. ... (7.6 g/l) and resveratrol production (1.5 mg/g) in hairy root of peanut. Our results demonstrate that the .... and proliferation of human retinal pigment epithelial cells via extracellular ...

  2. Photo-induced chemical reaction of trans-resveratrol.

    Science.gov (United States)

    Zhao, Yue; Shi, Meng; Ye, Jian-Hui; Zheng, Xin-Qiang; Lu, Jian-Liang; Liang, Yue-Rong

    2015-03-15

    Photo-induced chemical reaction of trans-resveratrol has been studied. UV B, liquid state and sufficient exposure time are essential conditions to the photochemical change of trans-resveratrol. Three principal compounds, cis-resveratrol, 2,4,6-phenanthrenetriol and 2-(4-hydroxyphenyl)-5,6-benzofurandione, were successively generated in the reaction solution of trans-resveratrol (0.25 mM, 100% ethanol) under 100 μW cm(-2) UV B radiation for 4h. cis-Resveratrol, originated from isomerization of trans-resveratrol, resulted in 2,4,6-phenanthrenetriol through photocyclisation reaction meanwhile loss of 2 H. 2,4,6-Phenanthrenetriol played a role of photosensitizer producing singlet oxygen in the reaction pathway. The singlet oxygen triggered [4+2] cycloaddition reaction of trans-resveratrol, and then resulted in the generation of 2-(4-hydroxyphenyl)-5,6-benzofurandione through photorearrangement and oxidation reaction. The singlet oxygen reaction was closely related to the substrate concentration of trans-resveratrol in solution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Resveratrol, a natural phytoalexin: A therapeutic promise for ...

    African Journals Online (AJOL)

    Resveratrol, a natural phytoalexin, has demonstrated a wide variety of biological activities, which make it a good candidate for treatment of diabetes mellitus. The present study was aimed to evaluate the properties of resveratrol (RSV) as an antidiabetic agent in streptozotocinnicotinamide (STZ-NIC) induced Type2 diabetes ...

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

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    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.

  5. 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.

  6. Physiological uptake and retention of radiolabeled resveratrol loaded gold nanoparticles (99mTc-Res-AuNP) in colon cancer tissue.

    Science.gov (United States)

    Kamal, Rozy; Chadha, Vijayta D; Dhawan, D K

    2018-01-31

    When tagged with a suitable radionuclide, the cancer targeting properties of trans-resveratrol could be utilized to locate cancerous sites in the body using radionuclide imaging technique. However, the polyphenol due to its rapid and extensive metabolism exhibits low bioavailability in vivo. The study was designed to enhance the cancer targeting efficacy of radiolabeled resveratrol using nano-based technology. Technetium-99m labeled resveratrol loaded gold nanoparticles (Res-AuNP) were synthesized, characterized and evaluated for their cancer targeting efficacy in HT29 colon cancer cells and in animal cancer model. Results of various investigations were compared to corresponding results obtained for 99m Tc-AuNP and 99m Tc-resveratrol. Cancer cell internalization observed for 99m Tc-Res-AuNP was significantly higher than that of 99m Tc-AuNP and 99m Tc-resveratrol. Also, a gradual rise in target to nontarget uptake with time was observed following i.v. administration of 99m Tc-Res-AuNP to colon tumor bearing rats, demonstrating better in vivo targeting of colon adenocarcinoma with 99m Tc-Res-AuNP when compared to 99m Tc-resveratrol. Copyright © 2018. Published by Elsevier Inc.

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

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    Seyed Jalal Hosseinimehr

    2014-01-01

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

  8. Resveratrol vs. calorie restriction: data from rodents to humans.

    Science.gov (United States)

    Lam, Yan Y; Peterson, Courtney M; Ravussin, Eric

    2013-10-01

    Calorie restriction extends lifespan and confers metabolic benefits similar to the effect of lifestyle interventions. Poor compliance to long-term dietary restriction, however, hinders the success of this approach. Evidence is now persuasive for a role of resveratrol supplementation (a polyphenol in red grapes) as potential alternative to calorie restriction. This review summarizes the latest literature on the effects and the molecular mechanisms by which calorie restriction and resveratrol confer health benefits. Resveratrol activates SIRT1 and the associated improvement in energy utilization and insulin sensitivity closely resembles the benefits of calorie restriction. Current data largely support resveratrol as a potential calorie restriction mimetic to improve metabolic and probably functional health. Future studies which characterize the bioavailability and efficacy of resveratrol supplementation are critical to provide evidence for its long-term health benefits. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    Science.gov (United States)

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

    2015-01-01

    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

  10. Implications of Resveratrol on Glucose Uptake and Metabolism.

    Science.gov (United States)

    León, David; Uribe, Elena; Zambrano, Angara; Salas, Mónica

    2017-03-07

    Resveratrol-a polyphenol of natural origin-has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes.

  11. Resveratrol Increases Serum BDNF Concentrations and Reduces Vascular Smooth Muscle Cells Contractility via a NOS-3-Independent Mechanism

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    Michał Wiciński

    2017-01-01

    Full Text Available Resveratrol is a polyphenol that presents both antineuroinflammatory properties and the ability to interact with NOS-3, what contributes to vasorelaxation. Brain-derived neurotrophic factor (BNDF, a molecule associated with neuroprotection in many neurodegenerative disorders, is considered as an important element of maintaining stable cerebral blood flow. Vascular smooth muscle cells (VSMCs are considered to be an important element in the pathogenesis of neurodegeneration and a potential preventative target by agents which reduce the contractility of the vessels. Our main objectives were to define the relationship between serum and long-term oral resveratrol administration in the rat model, as well as to assess the effect of resveratrol on phenylephrine- (PHE- induced contraction of vascular smooth muscle cells (VSMCs. Moreover, we attempt to define the dependence of contraction mechanisms on endothelial NO synthase. Experiments were performed on Wistar rats (n=17 pretreated with resveratrol (4 weeks; 10 mg/kg p.o. or placebo. Serum BDNF levels were quantified after 2 and 4 weeks of treatment with ELISA. Contraction force was measured on isolated and perfused tail arteries as the increase of perfusion pressure with a constant flow. Values of serum BNDF in week 0 were 1.18±0.12 ng/mL (treated and 1.17±0.13 ng/mL (control (p = ns. After 2 weeks of treatment, BDNF in the treatment group was higher than in controls, 1.52±0.23 ng/mL and 1.24±0.13 ng/mL, respectively. (p=0.02 Following 4 weeks of treatment, BDNF values were higher in the resveratrol group compared to control 1.64±0.31 ng/mL and 1.32±0.26 ng/mL, respectively (p=0.031. EC50 values obtained for PHE in resveratrol pretreated arteries were significantly higher than controls (5.33±1.7 × 10−7 M/L versus 4.53±1.2 × 10−8 M/L, p<0.05. These results show a significant increase in BDNF concentration in the resveratrol pretreated group. The reactivity of resistant

  12. Resveratrol, 4' Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health.

    Science.gov (United States)

    Lephart, Edwin D

    2017-06-03

    Phytochemicals are botanical compounds used in dermatology applications as cosmeceuticals to improve skin health. Resveratrol and equol are two of the best-known polyphenolic or phytoestrogens having similar chemical structures and some overlapping biological functions to 17β-estradiol. Human skin gene expression was reviewed for 28 different biomarkers when resveratrol, 4' acetoxy resveratrol (4AR), R -equol, racemic equol or S -equol were tested. Sirtuin 1 activator (SIRT 1) was stimulated by resveratrol and 4AR only. Resveratrol, R -equol and racemic equol were effective on the aging biomarkers proliferating cell nuclear factor (PCNA), nerve growth factor (NGF), 5α-reductase and the calcium binding proteins S100 A8 and A9. Racemic equol and 4AR displayed among the highest levels for the collagens, elastin and tissue inhibitor of the matrix metalloproteinase 1 (TIMP 1). S -equol displayed the lowest level of effectiveness compared to the other compounds. The 4AR analog was more effective compared to resveratrol by 1.6-fold. R -equol and racemic equol were almost equal in potency displaying greater inhibition vs. resveratrol or its 4' analog for the matrix metalloproteinases (MMPs), but among the inflammatory biomarkers, resveratrol, 4AR, R -equol and racemic equol displayed high inhibition. Thus, these cosmeceuticals display promise to improve dermal health; however, further study is warranted to understand how phytochemicals protect/enhance the skin.

  13. 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 ...

  14. Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock.

    Science.gov (United States)

    Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B; Baur, Joseph A; Sims, Carrie A

    2015-08-01

    Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer's (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood urea nitrogen, and serum creatinine values did not differ between resuscitation strategies. Resuscitation with RSV significantly restored renal mitochondrial

  15. Resveratrol induces sumoylated COX-2-dependent anti-proliferation in human prostate cancer LNCaP cells.

    Science.gov (United States)

    Cheng, Tsai-Mu; Chin, Yu-Tang; Ho, Yih; Chen, Yi-Ru; Yang, Yung-Ning; Yang, Yu-Chen; Shih, Ya-Jang; Lin, Ting-I; Lin, Hung-Yun; Davis, Paul J

    2018-02-01

    Cyclooxygenase (COX)-2 has been implicated in cancer development. However, resveratrol-induced nuclear accumulation of COX-2 enhances p53-dependent anti-proliferation in different types of cancers. Treatment with resveratrol leads to phosphorylation and nuclear translocation of mitogen-activated protein kinase (ERK1/2), and accumulation of nuclear COX-2 to complex with pERK1/2 and p53. The consequence is Ser-15 phosphorylation of p53 (pSer15-p53), and induction of anti-proliferation in cancer cells. We investigated the mechanisms by which resveratrol-inducible COX-2 facilitates p53-dependent anti-proliferation in prostate cancer LNCaP cells. Resveratrol treatment caused nuclear accumulation and complexing of ERK1/2, pSer15-p53 and COX-2 which was activated ERK1/2-dependent. Knockdown of SUMO-1 by shRNA also reduced nuclear accumulation of COX-2. Inhibition of nuclear accumulation by the COX-2 specific inhibitor, NS-398, inhibited co-localization of nuclear COX-2 and SUMO-1. Similar results were observed in the PD98059-treated cells. Finally, inhibition of SUMO-1 expression also reduced resveratrol-induced expression of pro-apoptotic genes but increased the expression of proliferative genes. In summary, these results demonstrate that inducible COX-2 associates with phosphorylated ERK1/2 to induce the phosphorylation of Ser-15 in p53 and then complexes with p53 and SUMO-1 which binds to p53-responsive pro-apoptotic genes to enhance their expression. The inhibition of COX-2 expression and activity significantly blocks the pro-apoptotic effect of resveratrol. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

    Directory of Open Access Journals (Sweden)

    Borhane Annabi

    2012-01-01

    Full Text Available The occurrence of a functional relationship between the release of metalloproteinases (MMPs and the expression of cyclooxygenase (COX-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB, increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA, a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1.

  17. Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: an in vitro approach.

    Directory of Open Access Journals (Sweden)

    Diana Serra

    Full Text Available Many advances have been recently made focused on the valuable help of dietary polyphenols in chronic inflammatory diseases. On the other hand, current treatment options for intestinal bowel disease patients are unsatisfying and, for this reason, it is estimated that many patients use dietary supplements to achieve extra benefits.The aim of this work was to analyze under a mechanistic perspective the anti-inflammatory potential of resveratrol, a natural polyphenolic compound, and to compare it with a pharmaceutical agent, 5-aminosalicylic acid, using the intestinal HT-29 cell line, as a cellular model.In the present study, HT-29 colon epithelial cells were pre-treated with 25 µM resveratrol and/or 500 µM 5-aminosalicylic acid and then exposed to a combination of cytokines (IL-1α, TNF-α, IFN-γ for a certain period of time. Our data showed that resveratrol, used in a concentration 20 times lower than 5-aminosalicylic acid, was able to significantly reduce NO and PGE2 production, iNOS and COX-2 expression and reactive oxidant species formation induced by the cytokine challenge. However, as already verified with 5-aminosalicylic acid, in spite of not exhibiting any effect on IkB-α degradation, resveratrol down-regulated JAK-STAT pathway, decreasing the levels of activated STAT1 in the nucleus. Additionally, resveratrol decreased the cytokine-stimulated activation of SAPK/JNK pathway but did not counteract the cytokine-triggered negative feedback mechanism of STAT1, through p38 MAPK.Taken together, our results show that resveratrol may be considered a future nutraceutical approach, promoting remission periods, limiting the inflammatory process and preventing colorectal cancer, which is common in these patients.

  18. Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats

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    Sevtap Aydın

    2016-12-01

    Full Text Available Background: The increases of free radicals have been proposed to be involved in the pathogenesis of sepsis, which leads to multiple-organ dysfunction syndromes. The uses of antioxidants as a complementary tool in the medical care of oxidative stress-related diseases have attracted attention of researchers. Resveratrol (RV has suggested being antioxidant, anti-proliferative, and anti-inflammatory effects in various experimental models and clinical settings. Aims: This study was undertaken to evaluate the protective effects of RV on oxidative DNA damage induced by sepsis in the liver and kidney tissues of Wistar albino rats. Study Design: Animal experimentation. Methods: Four experimental groups consisting of eight animals for each was created using a total of thirty-two male Wistar albino rats. Sham group was given 0.5 mL of saline intra-peritoneal (ip only following laparatomy. Sepsis group was given 0.5 mL saline ip only following the induction of sepsis. RV-treated group was given a dose of 100 mg/kg ip RV in 0.5 mL saline following laparatomy. RV-treated sepsis group was given 100 mg/kg ip RV in 0.5 mL saline following the induction of sepsis. A model of sepsis was created by cecal ligation and puncture technique. In the liver and kidney tissues, oxidative stress parameters (malondialdehyde (MDA, reduced glutathione (GSH, superoxide dismutase (SOD, glutathione peroxidase (GPX and a proinflammatory cytokine (tumor necrosis factor alpha (TNF-alpha, were evaluated spectrophotometrically and DNA damage was determined by the alkaline single cell gel electrophoresis (comet assay technique using formamidopyrimidine DNA glycosylase protein. Results: In the RV-treated sepsis group, the levels of MDA and TNF-alpha were lower and GSH levels, SOD and GPX activities were higher than in the septic rats (p<0.05. RV treatment significantly reduced the sepsis-induced oxidative DNA damage in the liver and kidney cells (p<0.05. Conclusion: It is suggested that

  19. Physicochemical properties and antioxidant activities of Korean traditional alcoholic beverage, yakju, enriched with mulberry.

    Science.gov (United States)

    Kwak, Eun Jung; Lee, Ji Yeon; Choi, Il Sook

    2012-07-01

    Mulberry fruits (Morus alba L.), rich in health beneficial compounds such as polyphenols, flavonoids, and anthocyananis, have traditionally been used as nutritional foodstuffs and fork medicines. In this study, physicochemical properties and antioxidant activities of a traditional Korean alcoholic beverage ``yakju'' enriched with mulberry were evaluated. The beverage was enriched with smoothies prepared from Korean mulberry cultivars of Cheongilppong (CP), Suwonppong (SP), and Daesungppong (DP). In comparison to the control, an increase in alcohol content and total acidity and a decrease in sugar level in yakju enriched with mulberry were observed during 15 d of fermentation. The total polyphenol and total flavonoid content increased in the following order: DP yakju > SP yakju > CP yakju > control yakju. In contrast, the anthocyanin content decreased during the fermentation periods. The trans-resveratrol content of mulberry yakju increased during the fermentation and the resveratrol content of DP yakju (0.24 mg/L) was significantly higher than that of SP yakju (0.21 mg/L) and CP yakju (0.14 mg/L) on the 15th day of fermentation (P traditional Korean alcoholic beverage ``yakju'' enriched with mulberry were investigated. This analysis is important for the potential applications of mulberry yakju as functional alcoholic drinks. © 2012 Institute of Food Technologists®

  20. 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.

  1. Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol.

    Science.gov (United States)

    Zahlten, Janine; Kim, Ye-Ji; Doehn, Jan-Moritz; Pribyl, Thomas; Hocke, Andreas C; García, Pedro; Hammerschmidt, Sven; Suttorp, Norbert; Hippenstiel, Stefan; Hübner, Ralf-Harto

    2015-06-01

    Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide. During pneumococcal pneumonia, the human airway epithelium is exposed to large amounts of H2O2 as a product of host and pathogen oxidative metabolism. Airway cells are known to be highly vulnerable to oxidant damage, but the pathophysiology of oxidative stress induced by S. pneumoniae and the role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant systems of the host are not well characterized. For gluthation/gluthathion disulfide analysis BEAS-2B cells, primary broncho-epithelial cells (pBEC), explanted human lung tissue and mouse lungs were infected with different S. pneumoniae strains (D39, A66, R6x, H2O2/pneumolysin/LytA- deficient mutants of R6x). Cell death was proven by LDH assay and cell viability by IL-8 ELISA. The translocation of Nrf2 and the expression of catalase were shown via Western blot. The binding of Nrf2 at the catalase promoter was analyzed by ChIP. We observed a significant induction of oxidative stress induced by S. pneumoniae in vivo, ex vivo, and in vitro. Upon stimulation, the oxidant-responsive transcription factor Nrf2 was activated, and catalase was upregulated via Nrf2. The pneumococci-induced oxidative stress was independent of S. pneumoniae-derived H2O2 and pneumolysin but depended on the pneumococcal autolysin LytA. The Nrf2 inducer resveratrol, as opposed to catalase, reversed oxidative stress in lung epithelial cells. These observations indicate a H2O2-independent induction of oxidative stress in lung epithelial cells via the release of bacterial factors of S. pneumoniae. Resveratrol might be an option for prevention of acute lung injury and inflammatory responses observed in pneumococcal pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

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    Devaraj Ezhilarasan

    2014-09-01

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

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

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    Avni Kılıç

    2016-06-01

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

  4. Resveratrol, piperine and apigenin differ in their NADPH-oxidase inhibitory and reactive oxygen species-scavenging properties.

    Science.gov (United States)

    Whitehouse, Scott; Chen, Pei-Lin; Greenshields, Anna L; Nightingale, Mat; Hoskin, David W; Bedard, Karen

    2016-11-15

    Many plant-derived chemicals have been studied for their potential benefits in ailments including inflammation, cancer, neurodegeneration, and cardiovascular disease. The health benefits of phytochemicals are often attributed to the targeting of reactive oxygen species (ROS). However, it is not always clear whether these agents act directly as antioxidants to remove ROS, or whether they act indirectly by blocking ROS production by enzymes such as NADPH oxidase (NOX) enzymes, or by influencing the expression of cellular pro- and anti- oxidants. Here we evaluate the pro- and anti-oxidant and NOX-inhibiting qualities of four phytochemicals: celastrol, resveratrol, apigenin, and piperine. This work was done using the H661 cell line expressing little or no NOX, modified H661 cells expressing NOX1 and its subunits, and an EBV-transformed B-lymphoblastoid cell line expressing endogenous NOX2. ROS were measured using Amplex Red and nitroblue tetrazolium assays. In addition, direct ROS scavenging of hydrogen peroxide or superoxide generated were measured using Amplex Red and methyl cypridina luciferin analog (MCLA). Of the four plant-derived compounds evaluated, only celastrol displayed NOX inhibitory activities, while celastrol and resveratrol both displayed ROS scavenging activity. Very little impact on ROS was observed with apigenin, or piperine. The results of this study reveal the differences that exist between cell-free and intracellular pro-oxidant and antioxidant activities of several plant-derived compounds. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. 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.

  6. Genotoxic, radioprotective and radiosensitizing effect of curcumin and trans-resveratrol in vitro cultures of human lymphocytes

    International Nuclear Information System (INIS)

    Fisher, V.A.; Tirsa Muñoz, B.; Sebastià, N.; Gómez-Cabrero, L.; La Parra, V.; Hervás, D.; Rodrigo, R.; Villaescusa, J.I.; Soriano, J.M.; Montoro, A.

    2015-01-01

    Curcumin and trans-resveratrol are natural polyphenol compounds. Curcumin is obtained from the rhizomes of the Curcumin plant (Curcuma longa), while trans-resveratrol is found in grapes, blackberries and other types of berry. These compounds have antioxidant, anti-inflammatory, immunostimulant and anticarcinogenic properties among others. In addition, they are also known for their radiomodulating properties since they are capable of providing radioprotection or radiosensitization for normal or tumours cells depending on different factors. This dual action may be the result of their properties, such as free radicals scavenging, as well as their influence on cell cycle checkpoints or control mechanisms. These are activated in response to the genetic damage induced by radiation. Despite the many beneficial properties attributed to these polyphenol compounds, some studies suggest that they are able to be genotoxic agents for some cellular lines. The results obtained indicate that both compounds possess a radioprotective effect on the lymphocytes of peripheral blood in the quiescent phase of the cellular cycle (G0). Nevertheless, they are capable of induce radiosensitivity on these type of cells in the growth phase (G2), and in addition, a different genotoxic effect can be seen according to the concentration of each compound. This study suggests, therefore, that curcumin and trans-resveratrol are able to exert a triple effect, genotoxic, radioprotective and radiosensitizing on in vitro cultures of human lymphocytes depending on the study parameters. [es

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

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    Brigitte Gonthier

    2012-01-01

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

  8. Resveratrol Interferes with Fura-2 Intracellular Calcium Measurements.

    Science.gov (United States)

    Kopp, Richard F; Leech, Colin A; Roe, Michael W

    2014-03-01

    Resveratrol, a naturally occurring polyphenol found in some fruits and especially in grapes, has been reported to provide diverse health benefits. Resveratrol's mechanism of action is the subject of many investigations, and some studies using the ratiometric calcium indicator Fura-2 suggest that it modulates cellular calcium responses. In the current study, contradictory cellular calcium responses to resveratrol applied at concentrations exceeding 10 μM were observed during in vitro imaging studies depending on the calcium indicator used, with Fura-2 indicating an increase in intracellular calcium while Fluo-4 and the calcium biosensor YC3.60 indicated no response. When cells loaded with Fura-2 were treated with 100 μM resveratrol, excitation at 340 nm resulted in a large intensity increase at 510 nm, but the expected concurrent decline with 380 nm excitation was not observed. Pre-treatment of cells with the calcium chelator BAPTA-AM did not prevent a rise in the 340/380 ratio when resveratrol was present, but it did prevent an increase in 340/380 when ATP was applied, suggesting that the resveratrol response was an artifact. Cautious data interpretation is recommended from imaging experiments using Fura-2 concurrently with resveratrol in calcium imaging experiments.

  9. Resveratrol as MDR reversion molecule in breast cancer: An overview.

    Science.gov (United States)

    Alamolhodaei, Nafiseh Sadat; Tsatsakis, Aristidis M; Ramezani, Mohammad; Hayes, A Wallace; Karimi, Gholamreza

    2017-05-01

    Breast cancer is the most common cause of cancer mortality among women worldwide; therefore, a strategy to defeat breast cancer is an extremely important medical issue. One of the major challenges in this regard is multidrug resistance (MDR). Resveratrol, a well-known phytoestrogen, may be helpful as part of an overall strategy to defeat breast cancer. The mixed agonist and antagonist role of resveratrol for the estrogen receptor makes it a controversial but interesting molecule in cancer therapy, especially in hormone dependent cancers. Several in vitro investigations have suggested that resveratrol can reverse multidrug resistance. However, poor bioavailability of resveratrol is a potential limitation for resveratrol treatment and cancer outcome in vivo. Fortunately, combination therapy with other selected compounds improves resveratrol's bioavailability and/or a delay in its metabolism. This review summaries the available published literature dealing with the effects of resveratrol on multidrug resistance in cancer and more specifically, breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy

    Science.gov (United States)

    Armour, Sean M.; Baur, Joseph A.; Hsieh, Sherry N.; Land-Bracha, Abigail; Thomas, Sheila M.; Sinclair, David A.

    2009-01-01

    Resveratrol is a plant-derived polyphenol that promotes health and disease resistance in rodent models, and extends lifespan in lower organisms. A major challenge is to understand the biological processes and molecular pathways by which resveratrol induces these beneficial effects. Autophagy is a critical process by which cells turn over damaged components and maintain bioenergetic requirements. Disruption of the normal balance between pro- and anti-autophagic signals is linked to cancer, liver disease, and neurodegenerative disorders. Here we show that resveratrol attenuates autophagy in response to nutrient limitation or rapamycin in multiple cell lines through a pathway independent of a known target, SIRT1. In a large-scalein vitro kinase screen we identified p70 S6 kinase (S6K1) as a target of resveratrol. Blocking S6K1 activity by expression of a dominant-negative mutant or RNA interference is sufficient to disrupt autophagy to a similar extent as resveratrol. Furthermore, co-administration of resveratrol with S6K1 knockdown does not produce an additive effect. These data indicate that S6K1 is important for the full induction of autophagy in mammals and raise the possibility that some of the beneficial effects of resveratrol are due to modulation of S6K1 activity. PMID:20157535

  11. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy.

    Science.gov (United States)

    Armour, Sean M; Baur, Joseph A; Hsieh, Sherry N; Land-Bracha, Abigail; Thomas, Sheila M; Sinclair, David A

    2009-06-03

    Resveratrol is a plant-derived polyphenol that promotes health and disease resistance in rodent models, and extends lifespan in lower organisms. A major challenge is to understand the biological processes and molecular pathways by which resveratrol induces these beneficial effects. Autophagy is a critical process by which cells turn over damaged components and maintain bioenergetic requirements. Disruption of the normal balance between pro- and anti-autophagic signals is linked to cancer, liver disease, and neurodegenerative disorders. Here we show that resveratrol attenuates autophagy in response to nutrient limitation or rapamycin in multiple cell lines through a pathway independent of a known target, SIRT1. In a large-scalein vitro kinase screen we identified p70 S6 kinase (S6K1) as a target of resveratrol. Blocking S6K1 activity by expression of a dominant-negative mutant or RNA interference is sufficient to disrupt autophagy to a similar extent as resveratrol. Furthermore, co-administration of resveratrol with S6K1 knockdown does not produce an additive effect. These data indicate that S6K1 is important for the full induction of autophagy in mammals and raise the possibility that some of the beneficial effects of resveratrol are due to modulation of S6K1 activity.

  12. mTOR: more targets of resveratrol

    DEFF Research Database (Denmark)

    Widlund, Anne Lykkegaard; Vang, Ole; Baur, Joseph

    2013-01-01

    Resveratrol (RSV) is a natural polyphenol produced by plants and is proposed to have multiple beneficial effects on health. In recent years, the interest in this molecule has increased nearly exponentially following the major findings that RSV (I) is chemo-preventive in some cancer models, (II......) is cardio-protective and (III) has positive effects on metabolism in mammals and increases lifespan in lower organisms. Mechanistic target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. As a part of the mTORC1 and mTORC2 complexes, the mTOR kinase...

  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. 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.

    Science.gov (United States)

    Bulku, Elida; Zinkovsky, Daniel; Patel, Payal; Javia, Vishal; Lahoti, Tejas; Khodos, Inna; Stohs, Sidney J; Ray, Sidhartha D

    2010-01-01

    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 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 combination of

  15. 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

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

    DEFF Research Database (Denmark)

    Mojsoska, Biljana; Xu, Jin

    2013-01-01

    was developed to obtain high-purity anthocyanins in the extract. The antioxidative activity of the extract, the anthocyanin-rich fraction (AF) was determined by 1,1-diphenyl-2-picrylhydrazyl radical and ferric-reducing ability of plasma along with resveratrol as a reference. The immunomodulation properties were......, whereas AF only had a slight effect in reducing IL-10. These results demonstrated that there was no major relationship between the antioxidative effect and immunomodulation capacities of AF and resveratrol. The immunomodulatory activity of the extract is associated with bioactive compounds in Aronia other......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...

  17. Resveratrol reduces prostaglandin E1-stimulated osteoprotegerin synthesis in osteoblasts: suppression of stress-activated protein kinase/c-Jun N-terminal kinase.

    Science.gov (United States)

    Yamamoto, Naohiro; Otsuka, Takanobu; Kuroyanagi, Gen; Kondo, Akira; Kainuma, Shingo; Nakakami, Akira; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Tokuda, Haruhiko

    2015-01-01

    Resveratrol, a natural polyphenol mainly existing in red grapes and berries, possesses beneficial effects on human being. We have previously reported that prostaglandin E1 (PGE1) stimulates vascular endothelial growth factor synthesis via activation of p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) but not p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the PGE1-effect on osteoprotegerin (OPG) synthesis and the effect of resveratrol on the synthesis in MC3T3-E1 cells. PGE1 induced the expression levels of OPG mRNA and stimulated the OPG release. Resveratrol significantly reduced the PGE1-induced OPG release and the mRNA expression. SRT1720, an activator of SIRT1, suppressed the release of OPG. The protein levels of SIRT1 were not up-regulated by resveratrol with or without PGE1. Both SB203580 and SP600125, a specific p38 MAP kinase inhibitor and a specific SAPK/JNK inhibitor, respectively, but not PD98059, a specific MEK inhibitor, reduced the PGE1-stimulated OPG release. Resveratrol or SRT1720 failed to affect the phosphorylation of p38 MAP kinase. On the contrary, PGE1-induced phosphorylation of SAPK/JNK was significantly attenuated by both resveratrol and SRT1720. Our results strongly suggest that resveratrol inhibits PGE1-stimulated OPG synthesis via suppressing SAPK/JNK but not p38 MAP kinase in osteoblasts. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice.

    Directory of Open Access Journals (Sweden)

    Ellen Gerhardt

    Full Text Available Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD and Parkinson's disease (PD. Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD.

  19. The effects of dietary phenolic compounds on cytokine and antioxidant production by A549 cells.

    Science.gov (United States)

    Gauliard, Benoit; Grieve, Douglas; Wilson, Rhoda; Crozier, Alan; Jenkins, Carol; Mullen, William D; Lean, Michael

    2008-06-01

    Levels of inflammatory cytokines are raised in chronic obstructive pulmonary disease (COPD). A diet rich in antioxidant vitamins may protect against the development of COPD. This study examined the effects of phenolic compounds and food sources on cytokine and antioxidant production by A549 cells. The effects of the following phenolic compounds on basal and interleukin (IL)-1-stimulated release of IL-8, IL-6, and reduced glutathione (GSH) were examined: resveratrol; Bouvrage, a commercially available raspberry juice (Ella Drinks Ltd., Alloa, Clacksmannanshire, UK); and quercetin 3'-sulfate. Purification of the raspberry juice by high-performance liquid chromatography gave three fractions: Fraction 1 contained phenolic acid and vitamin C, Fraction 2 contained flavonoids and ellagic acid, and Fraction 3 contained anthocyanins and ellagitannins. IL-8 production was increased in the presence of IL-1 (165 vs. 6,011 pg/mL, P or =50 micromol/mL significantly inhibited IL-8 and IL-6 production. Similar findings were made with raspberry juice at concentrations > or =25 microL/mL, and Fractions 1 and 3 were best able to inhibit IL-8 production. Quercetin 3'-sulfate, at 25 micromol/mL, inhibited IL-8 and IL-6 production. The changes observed in IL-8 were paralleled by changes in tumor necrosis factor-alpha. Thus, phenolic compounds can significantly alter cytokine and antioxidant production.

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

    Directory of Open Access Journals (Sweden)

    Zhenwen Zhang

    2011-03-01

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

  1. Synthetic resveratrol-curcumin hybrid derivative inhibits mitosis progression in estrogen positive MCF-7 breast cancer cells.

    Science.gov (United States)

    de Freitas Silva, Matheus; Coelho, Letícia Ferreira; Guirelli, Isadora Mitestainer; Pereira, Rodrigo Machado; Ferreira-Silva, Guilherme Álvaro; Graravelli, Graciana Y; Horvath, Renato de Oliveira; Caixeta, Ester Siqueira; Ionta, Marisa; Viegas, Claudio

    2018-03-02

    Curcumin (1) and resveratrol (2) are bioactive natural compounds that display wide pharmacological properties, including antitumor activity. However, their clinical application has been limited due to their low solubility and bioavailability. Nevertheless, independent studies have considered these compounds as interesting prototypes for developing new chemical structures useful for anticancer therapy. Here in, we report the synthesis of novel curcumin-like hydrazide analogues (3a and 3b), and a series of curcumin-resveratrol hybrid compounds (4a-f), and the evaluation of their cytotoxic potential on three tumor cell lines MCF-7 (breast), A549 (lung), and HepG2 (liver). Cell viability was significantly reduced in all tested cell lines when compounds 4c-4e were used. The IC 50 values for these compounds on MCF-7 cells were lower than those for curcumin, resveratrol, or curcumin combined with resveratrol. We evidenced that 4c promoted a drastic increase of G2/M population. The accumulation of cells in mitosis onset in treated cultures was due to, at least in part, the ability of 4c to modulate nuclear kinase proteins, which orchestrate important events in mitosis progression. We have also observed significant reduction of the relative RNAm abundance of CCNB1, PLK1, AURKA, AURKB in samples treated with 4c, with concomitant increase of CDKN1A (p21). Thus, compound 4c is a promising multi-target antitumor agent that should be considered for further in vivo studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Inhibition of human chronic myelogenous leukemia K562 cell growth following combination treatment with resveratrol and imatinib mesylate.

    Science.gov (United States)

    Wang, X J; Li, Y H

    2015-06-11

    To investigate the effect of treatment with resveratrol combined with imatinib mesylate on human chronic myelogenous leukemia K562 cell growth inhibition and apoptosis, in vitro cultured human chronic myelogenous leukemia K562 cells were incubated with different concentrations of resveratrol and imatinib mesylate when the cells were in the logarithmic phase. Next, the cell growth inhibition was evaluated using the MTT assay and cellular morphology observation. Apoptosis was determined using Annexin V fluorescein isothiocyanate/propidium iodide double staining. The results demonstrated that treatment with resveratrol (concentration-dependent) and imatinib mesylate showed significantly greater inhibition of K562 cell growth and a higher apoptosis rate of K562 cells than imatinib mesylate medication alone and the control group (P imatinib mesylate medication alone group showed significant inhibition of K562 cell growth and apoptosis rate of K562 cells compared to the control group (P imatinib mesylate and resveratrol are potent drug treatments for human chronic myelogenous leukemia, offering a promising means of inhibiting cell growth and apoptosis.

  3. Resveratrol in Patients with Minimal Hepatic Encephalopathy

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    Giulia Malaguarnera

    2018-03-01

    Full Text Available Background: Minimal Hepatic Encephalopathy (MHE is characterized by an impairment of social interaction, emotional behavior, sleep disorders, physical and mental symptoms, and diminished Quality of Life (QoL. The aim of our study is evaluating the potential liver health promoting a perspective of Resveratrol (RV activities and evaluate whether RV treatment may improve health related quality of life (HRQL and reduce depression and anxiety in patients with MHE. Methods: We evaluated depression using the Beck Depression Inventory test, anxiety with State-trait anxiety inventory test, quality of life through SF-36 test, and ammonia serum levels in 70 MHE patients that were randomized into two groups. Results: In the comparison between RV group and placebo group we observed a decrease in Back Depression Inventory (BDI (p < 0.001, in State-trait anxiety inventory (STAI (p < 0.001, and improve in physical function (p < 0.001, in role physical (p < 0.05, in body pain (p < 0.05, in general health (p < 0.001, in vitality (p < 0.05, and in social function (p < 0.001. Conclusions: Resveratrol showed efficacy in the treatment of depression, anxiety, and ammonia serum levels, and improved the quality of life Of MHE patients.

  4. Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring

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    Masato Tanaka

    2017-03-01

    Full Text Available Resveratrol (3,5,4-trihydroxystilbene is a natural polyphenolic compound found in grapes and red wine and has been shown to exert protective effects on the liver preventing lipid accumulation induced by a high-fat diet. However, no studies have shown that the nutritional resveratrol intake by the parental generation has modified lipogenesis in an adult offspring. The aim of this study was to investigate whether maternal resveratrol intake during lactation affects lipogenesis in adult male rat offspring, and if it does, what is the molecular mechanistic basis. Six male pups born from mothers given a control diets during lactation (CC group and six male pups born from mothers given a control diet as well as resveratrol during lactation (CR group were fed a standard diet until sacrifice at 36 weeks. Adult male offspring from mothers given resveratrol during lactation (CR group had lower body weight from the fourth week of lactation until adulthood, but no significant change was observed in the relative food intake. Low levels of plasma triacylglycerol were found in the CR group compared to the CC group. Histopathological analysis of the livers of adult male rat offspring revealed lipid accumulation in hepatocytes in the CC group, whereas lipid droplets were rare in the CR group. Hepatic protein levels of AMPK-phosphorylated at ser403, Sirt1, and Nampt in the CR group were upregulated significantly compared to the CC group. These results indicated the maternal resveratrol intake during lactation-induced activation of AMPK through Sirt1 upregulation. In this study, significant upregulation of the levels of precursor of sterol regulatory element binding protein-1c (SREBP-1c and downregulation of the ratio of active-SREBP-1c/precusor-SREBP-1c were observed in the CR group compared to the CC group. These results suggested that proteolytic processing of SREBP-1c was suppressed by AMPK in the livers of the CR group. It is well known that SREBP-1c

  5. Resveratrol Inhibits Cisplatin-Induced Epithelial-to-Mesenchymal Transition in Ovarian Cancer Cell Lines

    Science.gov (United States)

    Baribeau, Sébastien; Chaudhry, Parvesh; Parent, Sophie; Asselin, Éric

    2014-01-01

    Background Many patients diagnosed with ovarian cancer experience recurrence and metastasis, two aspects that will often cause their demise. Epithelial-to-mesenchymal transition (EMT) is a key process involved in cancer progression. With increasing evidence linking Cisplatin and EMT, we wanted to identify a compound able to counter EMT progression when cancer cells are treated with Cisplatin. Methodology/Principal Findings Cell death was evaluated by cytometry with Annexin V/PI staining in A2780 and A2780CP cells. Ovarian cancer cell lines were treated with Cisplatin (24 h, 10 µM) and different concentrations of Resveratrol to evaluate its effect on Cisplatin-induced EMT using Western Blot and RT-PCR analysis. Morphological studies and wound healing assay to evaluate cell motility were performed using 72 h Cisplatin treatment with A2780 and A2780CP cells. Densitometry was done on Western Blot and PCR results, and statistical significance was determined using One-Way ANOVA followed by Tukey post-hoc test. Our results show that Cisplatin induced EMT-associated morphological changes in the A2780 ovarian cancer cell line and to a lesser extent in its Cisplatin-resistant counterpart A2780CP. Resveratrol caused cell death in A2780 and A2780CP cell lines in an apoptotic-independent manner. Resveratrol inhibited Cisplatin-induced Snail expression by reducing the Erk pathway activation, reverted morphological changes induced by Cisplatin and decreased cell migration. Conclusions These results indicate that Resveratrol has interesting potential to prevent Cisplatin-induced EMT in ovarian cancer cells. By increasing cell death, it also represents an inviting approach as adjuvant therapy to be used with chemotherapy. Using Erk pathway inhibitors could also prove helpful in ovarian cancer treatment to reduce the risk of metastasis. PMID:24466305

  6. Cellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved osseointegration

    Science.gov (United States)

    Pandele, A. M.; Neacsu, P.; Cimpean, A.; Staras, A. I.; Miculescu, F.; Iordache, A.; Voicu, S. I.; Thakur, V. K.; Toader, O. D.

    2018-04-01

    Covalent immobilization of resveratrol onto cellulose acetate polymeric membranes used as coating on a Mg-1Ca-0.2Mn-0.6Zr alloy is presented for potential application in the improvement of osseointegration processes. For this purpose, cellulose acetate membrane is hydrolysed in the presence of potassium hydroxide, followed by covalent immobilization of aminopropyl triethoxy silane. Resveratrol was immobilized onto membranes using glutaraldehyde as linker. The newly synthesised functional membranes were thoroughly characterized for their structural characteristics determination employing X-ray photoelectron spectroscopy (XPS), infrared spectroscopy (FT-IR), Raman spectroscopy, thermogravimetric analysis (TGA/DTG) and scanning electron microscopy (SEM) techniques. Subsequently, in vitro cellular tests were performed for evaluating the cytotoxicity biocompatibility of synthesized materials and also the osseointegration potential of obtained derivatised membrane material. It was demonstrated that both polymeric membranes support viability and proliferation of the pre-osteoblastic MC3T3-E1 cells, thus providing a good protection against the potential harmful effects of the compounds released from coated alloys. Furthermore, cellulose acetate membrane functionalized with resveratrol exhibits a significant increase in alkaline phosphatase activity and extracellular matrix mineralization, suggesting its suitability to function as an implant surface coating for guided bone regeneration.

  7. Design, synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol.

    Science.gov (United States)

    Du, Cheng; Dong, Ming-Hui; Ren, Yu-Jie; Jin, Lu; Xu, Cheng

    2017-09-01

    A new series of resveratrol heterocyclic analogs (4a-m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure-activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC 50  = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC 50  = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4'-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F 1 -ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.

  8. Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults - A randomized controlled trial.

    Science.gov (United States)

    Huhn, Sebastian; Beyer, Frauke; Zhang, Rui; Lampe, Leonie; Grothe, Jana; Kratzsch, Jürgen; Willenberg, Anja; Breitfeld, Jana; Kovacs, Peter; Stumvoll, Michael; Trampel, Robert; Bazin, Pierre-Louis; Villringer, Arno; Witte, A Veronica

    2018-03-13

    The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie-restriction mimicking effects. However, the evidence based on human interventional studies is scarce. We therefore aimed to determine the effects of resveratrol on memory performance, and to identify potential underlying mechanisms using a broad array of blood-based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra-high field magnetic resonance imaging (UHF-MRI). In this double-blind, randomized controlled trial, 60 elderly participants (60-79 years) with a wide body-mass index (BMI) range of 21-37 kg/m 2 were randomized to receive either resveratrol (200 mg/day) or placebo for 26 weeks (registered at ClinicalTrials.gov: NCT02621554). Baseline and follow-up assessments included the California Verbal Learning Task (CVLT, main outcome), the ModBent task, anthropometry, markers of glucose and lipid metabolism, inflammation and neurotrophins derived from fasting blood, multimodal neuroimaging at 3 and 7 T, and questionnaires to assess confounding factors. Multivariate repeated-measures ANOVA did not detect significant time by group effects for CVLT performance. There was a trend for preserved pattern recognition memory after resveratrol, while performance decreased in the placebo group (n.s., p = 0.07). Further exploratory analyses showed increases in both groups over time in body fat, cholesterol, fasting glucose, interleukin 6, high sensitive C-reactive protein, tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum, as well as decreases in physical activity, brain-derived neurotrophic factor and insulin-like growth factor 1 at follow-up, which were partly more pronounced after resveratrol. This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range. A non-significant trend

  9. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

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    Teng Ma

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

  10. Implications of Resveratrol on Glucose Uptake and Metabolism

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    David León

    2017-03-01

    Full Text Available Resveratrol—a polyphenol of natural origin—has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes.

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

    Science.gov (United States)

    Ma, Teng; Tan, Meng-Shan; Yu, Jin-Tai; Tan, Lan

    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 vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD. PMID:25525597

  12. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol.

    Science.gov (United States)

    Takeda, Mamoru; Takehana, Shiori; Sekiguchi, Kenta; Kubota, Yoshiko; Shimazu, Yoshihito

    2016-10-11

    Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  13. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

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    Mamoru Takeda

    2016-10-01

    Full Text Available Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  14. Diabetes-induced renal failure is associated with tissue inflammation and neutrophil gelatinase-associated lipocalin: Effects of resveratrol

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    Koca Halit B.

    2016-01-01

    Full Text Available Diabetes mellitus is a chronic inflammatory disease characterized by high blood glucose levels due to the absence of secretion of insulin or its inefficient use in the body. In this study, we investigated how resveratrol administration affects the renal functions and pro-inflammatory signaling pathway components in streptozotocin-induced diabetes in male Wistar rats. Rats were randomly divided into four groups: (1 control/vehicle; (2 control/20 mg/kg resveratrol; (3 diabetic/vehicle; and (4 diabetic/20 mg/kg resveratrol. In addition to renal glucose, lipid, angiopoietin-1 (ANG-1, asymmetric dimethylarginine (ADMA, erythropoietin (EPO, malondialdehyde (MDA and neutrophil gelatinase-associated lipocalin (NGAL content, the gene expressions of pro-inflammatory markers, including inducible nitric oxide synthase (iNOS, nuclear factor kappa B (NF-κB, nuclear factor (erythroid-derived 2 like-2 (Nrf2, and the protein contents of interleukins-1β,6,8 (IL-1β,6,8 and tumor necrosis factor-α (TNF-α were analyzed using qRT-PCR and ELISA, respectively. The rats in the diabetes group demonstrated significantly lower terminal body weight and renal ANG-1, but significantly higher renal glucose, cholesterol, triglyceride, ADMA and MDA concentrations. Diabetes triggered inflammation in kidney tissues, reflected as an increase in NGAL level. The renal inflammation observed in the diabetes group was associated with significant upregulation of components of the pro-inflammatory pathway, iNOS, NF-κB, Nrf2, IL-1β, IL-6, IL-8 and TNF-α. To some extent, resveratrol administration reversed the diabetes-induced changes in renal tissues, suggesting that resveratrol partially protected from diabetes-induced renal failure due to its restorative activities in tissue inflammation.

  15. Resveratrol, a component of wine and grapes, in the prevention of kidney disease.

    Science.gov (United States)

    Bertelli, Alberto A E; Migliori, Massamiliano; Panichi, Vincenzo; Origlia, Nicola; Filippi, Cristina; Das, Dipak K; Giovannini, Luca

    2002-05-01

    Ischemia is an inciting factor in 50% of incidences of acute renal failure, and it increases the risk of organ rejection after renal transplantation. We have previously demonstrated that resveratrol (RSV) reduces ischemia-reperfusion (I/R) injury of rat kidney both by antioxidant and anti-inflammatory mechanisms. However, a clear morphological demonstration of this activity has not been made. To answer this question we have performed a new set of experiments following the experimental protocol reported below to investigate the effects of I/R injury and RSV pretreatment on kidney morphology by computerized morphometric analysis. Both renal arteries were clamped for 40 minutes in 40 male Wistar rats (b.w. 220 +/- 20 g); 20 rats were pretreated with RSV 1 microM e.v. 40 minutes before clamping. All animals were reperfused for 24 hours and then sacrificed. Histological examination showed tissue conservation in treated rats. I/R-induced glomerular collapse (as revealed by mean glomerular volume and glomerular shape factor) was significantly reduced by RSV pretreatment. Capillary tuft/Bowman's capsule area ratio was enhanced in the I/R group suggesting tubular hypertension. RSV pre-treatments significantly reduced this parameter to the control value. The number of platelet clots in the capillary tuft and tubular necrosis were also reduced by RSV versus I/R group. L-NAME administration worsened both functional and structural damage. Finally, cGMP urinary levels were markedly reduced from 12.1 +/- 8.4 nmol/day to 0.10 +/- 0.10 nmol/day in the I/R group. RSV provided cGMP (5.01 +/- 1.5 nmol/day, P < 0.05). As expected, L-NAME administration significantly reduced cGMP in urine (0.71 +/- 0.6 nmol/day). The present study confirms the protective effect of RSV pretreatment in I/R injury of rat kidney and suggests multiple mechanisms of action.

  16. Beneficial effects of Resveratrol, present in grapes in the prevention and treatment of heart disease and failure

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    Ali Movahed

    2015-04-01

    Full Text Available Resveratrol (3, 5, 4- trihydroxystilbene is one of the natural polyphenolic bioactive compounds synthesized by plants to serve many functions, especially defense against fungal infections, environmental stresses and UV radiation. It is found mainly in grapes, green tea, peanuts and berries. This compound has recently received increased attention in medical research, due to its effects on prevention and treatment of many diseases, including cancer, cardiovascular disease, and metabolic syndrome. Over the past two decades, researchers from all over the world studied the beneficial effects of resveratrol against cardiovascular diseases and heart failure in different animal models. Importantly, the results of these studies have been promising and recently this knowledge has been translated into examining the efficacy of resveratrol in humans with heart failure. Since heart failure continues to be a significant cause of cardiovascular mortality in the developed and also developing countries, and despite different medicines available for the treatment of such common chronic systemic diseases, preventive measures to be necessary to combat the incidence of heart problems. In this review article the protective effects of resveratrol and its mechanisms of action on different metabolic pathways with respect to heart disease and failure will be discussed.

  17. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Sahebkar, Amirhossein

    2013-12-01

    A systematic review and meta-analysis of available evidence was conducted to obtain a conclusive result on the lipid-modulating effects of resveratrol. Seven randomized controlled trials with a total of 282 subjects (141 in each group) met the eligibility criteria. Overall, resveratrol supplementation had no significant effect on any of the lipid parameters assessed: total cholesterol (weighted mean difference [WMD] -8.70; 95% confidence interval [95% CI] -21.54-4.14; P = 0.18), low-density lipoprotein cholesterol (WMD -3.22; 95% CI -12.56-6.12); P = 0.50), high-density lipoprotein cholesterol (WMD -0.26; 95% CI -4.25-3.73; P = 0.90), and triglycerides (WMD -4.30; 95% CI -20.22-11.63; P = 0.60). These results were robust in sensitivity analysis and were not dependent on the resveratrol dose, the duration of supplementation, or the cardiovascular risk status of the population studied. While future large-scale, well-designed trials are warranted, the current evidence suggests that mechanisms other than hypolipidemic effects account for the established cardioprotective properties of resveratrol. © 2013 International Life Sciences Institute.

  18. Resveratrol and Pterostilbene Exhibit Anticancer Properties Involving the Downregulation of HPV Oncoprotein E6 in Cervical Cancer Cells

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    Kaushiki Chatterjee

    2018-02-01

    Full Text Available Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents in targeting cervical cancer cells, having low IC50 values in the µM range. They decrease clonogenic survival, reduce cell migration, arrest cells at the S-phase, and reduce the number of mitotic cells. These findings were significant, with pterostilbene often being more effective than resveratrol. Resveratrol and to a greater extent pterostilbene downregulates the HPV oncoprotein E6, induces caspase-3 activation, and upregulates p53 protein levels. Results point to a mechanism that may involve the downregulation of the HPV E6 oncoprotein, activation of apoptotic pathways, and re-establishment of functional p53 protein, with pterostilbene showing greater efficacy than resveratrol.

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

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    Caroline Peres Klein

    2016-01-01

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

  20. Resveratrol plays important role in protective mechanisms in renal disease - mini-review

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    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.

  1. 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.

  2. Pallidol, a resveratrol dimer from red wine, is a selective singlet oxygen quencher

    International Nuclear Information System (INIS)

    He Shan; Jiang Liyan; Wu Bin; Pan Yuanjiang; Sun Cuirong

    2009-01-01

    Pallidol is a naturally occurring resveratrol dimer from red wine with antioxidant and antifungal activities. In this report, with the use of the EPR spin-trapping technique, the scavenging and quenching effects of pallidol on reactive oxygen species (ROS) were investigated. The results demonstrated that pallidol showed strong quenching effects on singlet oxygen at very low concentrations, but it was ineffective to scavenge hydroxyl radicals or superoxide anions. Further kinetic study revealed that the reaction of pallidol with singlet oxygen had an extremely high rate constant (k a = 1.71 x 10 10 ). Therefore, pallidol is a potent and selective singlet oxygen quencher in aqueous systems. It may be used in singlet oxygen-mediated diseases as a pharmacological agent, which may contribute to the health beneficial effects of red wine.

  3. Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds

    International Nuclear Information System (INIS)

    Bisht, Kavita; Wagner, Karl-Heinz; Bulmer, Andrew C.

    2010-01-01

    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.

  4. Highly Efficient Biotransformation of Polydatin to Resveratrol by Snailase Hydrolysis Using Response Surface Methodology Optimization

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    Lian-Xue Zhang

    2013-08-01

    Full Text Available Resveratrol (RV, a dietary antioxidant polyphenolic compound found in grapes and red wine, exerts a wide variety of pharmacological activities. However, lower content in plants compared with polydatin (PD, the glucoside of RV limits its application in the food and pharmaceutical industries. In this paper, we carried out efficient biotransformation of PD to RV with 100% conversion yield by snailase hydrolysis. Moreover, response surface methodology (RSM was used to optimize the effects of the reaction temperature, enzyme load, and reaction time on the conversion process. Validation of the RSM model was verified by the good agreement between the experimental and the predicted RV yield values. The optimum preparation conditions were as follows: temperature of 62.0 °C, enzyme load of 6.6%, and reaction time of 96 min. The proposed method may be highly applicable for the enzymatic preparation of RV for medicinal purposes.

  5. Role of resveratrol in the management of insulin resistance and related conditions: Mechanism of action.

    Science.gov (United States)

    Abbasi Oshaghi, Ebrahim; Goodarzi, Mohammad Taghi; Higgins, Victoria; Adeli, Khosrow

    2017-06-01

    Resveratrol (RES), a well-known antioxidant, is present in numerous plant species and, as a result, is easily obtained through dietary intake of plant-based foods and beverages. Several studies suggest that RES has anti-carcinogenic, anti-microbial, and anti-viral effects. It may also have beneficial metabolic properties that result in mitigation of insulin resistance (IR) and related metabolic abnormalities, including dyslipidemia, hyperglycemia, and hyperinsulinemia through regulation of gene expression or the activity of rate-limiting enzymes. A large body of evidence supports the beneficial effects of RES in the management and treatment of IR, type 2 diabetes, and related complications through a multitude of mechanisms. This review article focuses on the mechanisms of action of RES, the mechanisms leading to improved insulin sensitivity, and its clinical role in the management and treatment of type 2 diabetes.

  6. Combination of Resveratrol and Zinc for Prostate Cancer Management

    Science.gov (United States)

    2013-05-01

    synergistic tumor suppressive response 7 Curcumin BP-induced lung cancer in mice Combination showed better chemopreventive response by maintaining adequate...zinc, and modulating Cox-2 and p21 level 25 Quercetin + Genistein + Apigenin + EGCG + Baicalein + Curcumin TRAMP mouse model of prostate cancer All...Resveratrol and curcumin In a recent study, Malhotra et al. assessed the ef- ficacy of combined supplementation of curcumin and resveratrol in benzo[a

  7. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Faghihzadeh, Forouzan; Adibi, Payman; Hekmatdoost, Azita

    2015-09-14

    Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

  8. The effects of resveratrol intervention on risk markers of cardiovascular health in overweight and obese subjects: a pooled analysis of randomized controlled trials.

    Science.gov (United States)

    Huang, Haohai; Chen, Guangzhao; Liao, Dan; Zhu, Yongkun; Pu, Rong; Xue, Xiaoyan

    2016-12-01

    Potential effects of resveratrol consumption on cardiovascular disease risk factors and body weight in overweight/obese adults have not been fully elucidated. Our present analysis was to evaluate the effects of resveratrol consumption on risk markers related to cardiovascular health in overweight/obese Individuals. Multiple literature databases were systematically searched, and 21 studies were included. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI), and heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. There were variations in reporting quality of included studies. Resveratrol intervention significantly lowered total cholesterol (WMD, -0.19 mmol/L; 95% CI, -0.32 to -0.06; P = 0.004), systolic blood pressure (WMD, -2.26 mmHg; 95% CI, -4.82 to -0.49; P = 0.02), and fasting glucose (WMD, -0.22 mmol/L; 95% CI, -0.42 to -0.03; P = 0.03). Heterogeneity was noted for these outcomes (35.6%, 38.7% and 71.4%, respectively). Our subgroup analysis showed significant reductions in total cholesterol, systolic blood pressure, diastolic blood pressure, glucose, and insulin in subjects ingesting higher dose of resveratrol (≥300 mg/day). Our finding provides evidence that daily resveratrol consumption might be a candidate as an adjunct to pharmacological management to better prevent and control cardiovascular disease in overweight/obese individuals. © 2016 World Obesity Federation.

  9. Liver δ-Aminolevulinate Dehydratase Activity is Inhibited by Neonicotinoids and Restored by Antioxidant Agents

    Directory of Open Access Journals (Sweden)

    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.

  10. Challenges in Analyzing the Biological Effects of Resveratrol

    DEFF Research Database (Denmark)

    Erdogan, Cihan Süleyman; Vang, Ole

    2016-01-01

    The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biolog......The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety...... research. Questions we address include: (1) Is the combinatorial effect of resveratrol and other compounds real? (2) What are the real and relevant doses of resveratrol after administration? and (3) Is it possible to estimate the preventive effect of resveratrol by clinical trials using standard...... experimental designs? The examples concerning resveratrol taken from the scientific literature are mainly from 2010 and later. The challenges pointed out in this review are similar to most naturally occurring bioactive compounds...

  11. Cardiovascular Protective Effects and Clinical Applications of Resveratrol.

    Science.gov (United States)

    Cho, Sanghyun; Namkoong, Kyung; Shin, Minji; Park, Jueun; Yang, Eunyeong; Ihm, Jinsoo; Thu, Vu Thi; Kim, Hyoung Kyu; Han, Jin

    2017-04-01

    Resveratrol is a naturally occurring phenol that is generated by plant species following injury or attack by bacterial and fungal pathogens. This compound was first described as the French Paradox in 1992. Later in 2003, resveratrol was reported to activate sirtuins in yeast cells. Recent experimental studies have found that resveratrol offers a variety of benefits that include both anticarcinogenic and anti-inflammatory effects in addition to the ability to reverse obesity, attenuate hyperglycemia and hyperinsulinemia, protect heart and endothelial function, and increase the life span. Multiple molecular targets are associated with the cardioprotective capabilities of resveratrol, and therefore, resveratrol has potential for a wide range of new therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, cardiac failure, and inflammatory alterations during aging. Expectations for application in human patients, however, suffer from a lack of sufficient clinical evidence in support of these beneficial effects. This article reviews recently reported basic research results that describe the beneficial effects of resveratrol in an attempt to condense the evidence observed in clinical trials and provide support for the future development of novel clinical therapeutics in patients with cardiovascular diseases.

  12. Resveratrol and inflammatory bowel disease: the evidence so far.

    Science.gov (United States)

    Nunes, Sandra; Danesi, Francesca; Del Rio, Daniele; Silva, Paula

    2017-12-01

    Despite the fact that inflammatory bowel disease (IBD) has still no recognised therapy, treatments which have proven at least mildly successful in improving IBD symptoms include anti-inflammatory drugs and monoclonal antibodies targeting pro-inflammatory cytokines. Resveratrol, a natural (poly)phenol found in grapes, red wine, grape juice and several species of berries, has been shown to prevent and ameliorate intestinal inflammation. Here, we discuss the role of resveratrol in the improvement of inflammatory disorders involving the intestinal mucosa. The present review covers three specific aspects of resveratrol in the framework of inflammation: (i) its content in food; (ii) its intestinal absorption and metabolism; and (iii) its anti-inflammatory effects in