ABSTRACT
Growing evidence indicates that oxidative stress plays an important role in the pathophysiology of many cardiovascular diseases, including atherosclerosis. In this context, the use of bioactive compounds with antioxidant action can bring health benefits, especially in the prevention and control of pathophysiological events. Studies suggest that the polyphenol trans-resveratrol can reduce oxidative stress by acting on the nuclear factor erythroid-2-related factor 2 (Nrf2) and this effect would be associated with dosage. Thus, the present study aimed to investigate the effect of different doses of trans-resveratrol on biomarkers related to atherosclerosis and oxidative stress. In the first step, 27 randomized clinical trials, which evaluated the effect of trans-resveratrol on atherosclerosis-related biomarkers, were classified according to their protocol characteristics and profile of each outcome. Biochemical data from 12 biomarkers were selected to calculate the net change (%). Using multivariate analysis, the trials were distributed into 3 clusters. The studies that composed Clusters II and III were more effective in improving blood pressure and reducing dyslipidemia, respectively. These studies were characterized by a longer intervention time (> 2 months) with doses of around 200-500 mg/day. These results showed that the effects of transresveratrol are mainly related to dosage and intervention time. Based on these results, two doses were selected to apply in an experimental protocol to investigate the effect of trans-resveratrol on hepatic oxidative stress biomarkers mediated by Nrf2 pathway. LDLr(-/-) mice were fed for 8 weeks on a standard diet, followed by over 24 weeks on a Western diet, both containing trans-resveratrol at doses of 250 mg/kg diet/day (low dose resveratrol, LRD) or 400 mg/kg diet/day (high dose resveratrol, HRD). A control group (CONT) was maintained without supplementation. In general, both doses of trans-resveratrol did not affect the body weight and lipid profile of the animals. Only the LRD group showed reduced levels of two important biomarkers of oxidative stress in the liver (GSH/GSSG ratio and malonaldehyde), besides to reduced expression of factor nuclear kappa B (NF-kB). However, contrary to our hypothesis, both doses reduced Nrf2 expression in the liver compared to the CONT group. Regarding inflammatory cytokines, no changes were observed in the levels of TNF-α and IL-10. Furthermore, both doses increased the level of the pro-inflammatory cytokine IL-6. Taken together, our results suggest that trans-resveratrol supplementation at doses lower than 500 mg/day may contribute to the reduction of biomarkers related to atherosclerosis and oxidative stress
Evidências crescentes indicam que o estresse oxidativo desempenha um papel importante na fisiopatologia de muitas doenças cardiovasculares, incluindo a aterosclerose. Nesse contexto, o uso de compostos bioativos com ação antioxidante pode trazer benefícios à saúde, principalmente na prevenção e controle de eventos fisiopatológicos. Estudos sugerem que o polifenol trans-resveratrol pode reduzir o estresse oxidativo atuando na via do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) e que esse efeito estaria associado a dosagem. Assim, o presente estudo teve como objetivo investigar o efeito de diferentes doses de trans-resveratrol sobre biomarcadores relacionados à aterosclerose e estresse oxidativo. Na primeira etapa, 27 ensaios clínicos randomizados, que avaliaram o efeito do trans-resveratrol em biomarcadores relacionados à aterosclerose, foram classificados de acordo com suas características de protocolo e perfil de cada resultado. Dados bioquímicos de 12 biomarcadores foram selecionados para calcular a variação líquida (%). Usando análise multivariada, os ensaios foram distribuídos em 3 Clusters. Os estudos que compuseram os Clusters II e III foram mais eficazes na melhora da pressão arterial e na redução da dislipidemia, respectivamente. Esses estudos foram caracterizados por um tempo de intervenção mais longo (> 2 meses) com doses de cerca de 200-500 mg/dia. Esses resultados mostraram que os efeitos do transresveratrol estão relacionados principalmente à dosagem e ao tempo de intervenção. Com base nesses resultados, duas doses foram selecionadas para aplicar em um protocolo experimental para investigar o efeito do trans-resveratrol em biomarcadores de estresse oxidativo hepático mediados pela via do Nrf2. Camundongos LDLr(-/-) foram alimentados por 8 semanas com dieta padrão, seguidos por mais de 24 semanas com Western diet, ambos contendo trans-resveratrol nas doses de 250 mg/kg de dieta/dia (baixa dose de resveratrol, LRD) ou 400 mg/kg de dieta/dia (alta dose de resveratrol, HRD). Um grupo controle (CONT) foi mantido sem suplementação. Em geral, ambas as doses de trans-resveratrol não afetaram o peso corporal e o perfil lipídico dos animais. Apenas o grupo LRD apresentou níveis reduzidos de dois importantes biomarcadores de estresse oxidativo no fígado (razão GSH/GSSG e malonaldeído), além da redução da expressão de fator nuclear kappa B (NF-kB). No entanto, ao contrário da nossa hipótese, ambas as doses reduziram a expressão de Nrf2 no fígado em comparação com o grupo CONT. Em relação às citocinas inflamatórias, não foram observadas alterações nos níveis de TNF-α e IL-10. Além disso, ambas as doses aumentaram o nível da citocina pró-inflamatória IL-6. Em conjunto, nossos resultados sugerem que a suplementação de trans-resveratrol em doses menores de 500 mg/dia podem contribuir para a redução de biomarcadores relacionados à aterosclerose e ao estresse oxidativo
Subject(s)
Animals , Male , Female , Mice , Biomarkers/analysis , Randomized Controlled Trials as Topic , Oxidative Stress/drug effects , Atherosclerosis/pathology , Resveratrol/adverse effects , Cardiovascular Diseases/prevention & control , NF-kappa B , Antioxidants/administration & dosageABSTRACT
Abstract Gut bacterial β-glucuronidase (GUS) can reactivate xenobiotics that exert enterohepatic circulation- triggered gastrointestinal tract toxicity. GUS inhibitors can alleviate drug-induced enteropathy and improve treatment outcomes. We evaluated the inhibitory effect of Polygonum cuspidatum Siebold & Zucc. and its major constituents against Escherichia coli GUS (EcGUS), and characterized the inhibitory mechanism of each of the components. Trans-resveratrol 4'-O-β-D-glucopyranoside (HZ-1) and (-)-epicatechin gallate (HZ-2) isolated from P. cuspidatum were identified as the key components and potent inhibitors. These two components displayed strong to moderate inhibitory effects on EcGUS, with Ki values of 9.95 and 1.95 μM, respectively. Results from molecular docking indicated that HZ-1 and HZ-2 could interact with the key residues Asp163, Ser360, Ile 363, Glu413, Glu504, and Lys 568 of EcGUS via hydrogen bonding. Our findings demonstrate the inhibitory effect of P. cuspidatum and its two components on EcGUS, which supported the further evaluation and development of P. cuspidatum and its two active components as novel candidates for alleviating drug-induced damage in the mammalian gut.
ABSTRACT
Gnetum gnemon L. (Melinjo) seeds have high trans-resveratrol, which was known to have poor skin absorption ability.This study was performed to evaluate the skin absorption of ionic liquid-melinjo seed extract (IL-MSE) loaded solidlipid nanoparticles (SLN). The SLNs was formulated with glyceryl monostearate as the lipid ingredient, ceteareth-25,ceteareth-6, stearyl alcohol, an aqueous phase, and 10% melinjo seed extract. The SLNs were prepared by modificationof high-pressure homogenization. The polydispersity index (PDI), zeta potential, entrapment efficiency (EE), particlesize (PS), and morphological scanning electron microscopy (SEM) were evaluated. The in vitro penetration of IL-MSESLN was carried out by using the Franz cell diffusion method. The SLNs formulations showed an average of particlessize about 794 nm, and with high lipid and surfactant, the content could contributing to high entrapment efficiencyto almost 89%. Even though the polydispersity index of SLN was 1.229, and zeta potential measurement was 62.56mV. Up to 45% of the trans-resveratrol penetrated through the skin after 8 hours of the test run. The IL-MSE loadedto SLNs could improve the absorption of trans-resveratrol through the skin.
ABSTRACT
Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or attack by fungi. The underutilization of soybean seed coat (Glycine max (L.) Merrill.) and tempeh, cheap Indonesia fermented food thus opens up a new opportunity for developing a Resveratrol-based medicine for Plants-Derived Neuroprotective Agents purposes. In this study, it was isolated from tempeh, ordinarily well-known as Indonesian soybean fermented food, and soybean seed coat. The finding of this compound was confirmed by TLC and HPLC analysis applying fluorescence detection. From this, the Rf-value for transresveratrol is 0.64. As eluent, a mixture of chloroform, ethyl acetate, and formic acid (2.5+1+0.1, v/v) was selected. In addition, retention time for tempeh was 14.467 and for soybean seed coat was 11.977. The extraction yield of resveratrol was 65.15 % in tempeh and 55.35 % in soybean seed coat. Resveratrol isolated from Tempeh and Soybean seed coat gave prevents some reaction by modulating intracellular signaling pathways: protein kinase C (PKC), a family of 12 serine/ threonine kinases and providing a new lead molecule for neuroprotective affects in addition to has prevented cell death by apoptosis.
El resveratrol es un estilbenoide, un tipo de fenol natural, y fitoalexina producida por varias plantas en respuesta a una lesión o ataque de hongos. La subutilización de la cubierta de la semilla de soja (Glycine max (L.) Merrill.) y el tempeh, alimento fermentado barato de Indonesia, abren una nueva oportunidad para obtener un medicamento a base de resveratrol para propósitos de desarrollo de agentes neuroprotectores derivados de plantas. En este estudio, se aisló el resveratrol del tempeh, generalmente conocido como alimento fermentado de soja de Indonesia y de la cubierta de la semilla de soja. El hallazgo de este compuesto se confirmó mediante análisis de TLC y HPLC aplicando detección de fluorescencia. A partir de esto, el valor de Rf para trans-resveratrol es 0,64. Como eluyente, se seleccionó una mezcla de cloroformo, acetato de etilo y ácido fórmico (2,5 + 1 + 0,1, v / v). Además, el tiempo de retención para el tempeh fue de 14,467 y para el revestimiento de semilla de soja fue de 11,977. El rendimiento de extracción del resveratrol fue del 65,15 % en tempeh y del 55,35 % en la cubierta de la semilla de soja. El resveratrol aislado de tempeh y de la cubierta de la semilla de soja previno reacciones mediante la modulación de ciertas vías de señalización intracelular: proteína quinasa C (PKC), una familia de 12 serina/treonin quinasas, proporcionando una nueva molécula de plomo con efectos neuroprotectores, además de prevenir la muerte celular por apoptosis.
Subject(s)
Animals , Mice , Soybeans/chemistry , Neuroprotective Agents/isolation & purification , Soy Foods/analysis , Resveratrol/isolation & purification , Seeds/chemistry , Cells, Cultured , Chromatography, High Pressure Liquid , Chromatography, Thin LayerABSTRACT
Aims: In Ivory Coast, Mezoneuron angolenseroots are well-known in traditional medicine for their efficiency in the treatment of diarrhoea. The goal of this study was to determine the antibacterial constituents of these roots.Methodology:The chemical investigations of the roots of the plant havebeen undertaken and the structure of isolated compounds was elucidated through spectral studies including IR, UV, MS, 1D-NMR (1H and 13C NMR) and 2D-NMR experiments (HSQC, HMBC, COSY, and NOESY). The isolated compounds were screened against three enteropathogenic bacteria, Vibrio cholerae, Salmonella typhiand Shiguella fleneii,usingmicrobroth dilution method. Results:These investigations conducted to the isolation of two sterols, two stilbenes, one phthalate,and one carbohydrate. All tested compoundsexcept Bis (2-methylheptyl) phtalate (2) were active against all pathogens with MICs and MBCs ranging from 312.50 to 625 mg/ml. Piceatannol (5) and Trans-resveratrol (3) were the most active compounds.Conclusion:The results from the current study confirm and justify the popular use of the roots of this plant in the treatment of infectiousdiarrhoea. All obtained compounds were isolated from this species for the first time.
ABSTRACT
Objective:To detect the anti-cancer component, trans-resveratrol in red wine by high performance liquid chromatography, and to determine the influence of environmental factors on its content. Methods: A method for determining trans-resveratrol in red wine by HPLC is described. The operating conditions were ZORBAX-C18 column(4.6 mm×250 mm, 5μm) at room temperature, 30%acetonitrile as mobile phase at a flow of 1ml/min and UV detection at 306 nm. Results:The content of trans-resveratrol in Changyu dry red wine and Great Wall Claret Cabernet are (1.01±0.03)mg/L and (2.36±0.02)mg/L, respectively. The results show that, sunlight, high temperature and poor seal condition can decrease the content of trans-resveratrol. Conclusion:The content of trans-resveratrol varies in different brands of red wine. Red wine should be stored in cool, dark and sealed conditions.
ABSTRACT
Background: Plant cell suspension culture of Vitis vinifera is a promising technology for investigating different factors that are able to induce and/or modify stilbenes biosynthesis. Jasmonates have been reported to play an important role in a signal transduction pathway that regulates defence responses as well as the production of secondary metabolites. In this study, 2, 3-dihydroxypropyl jasmonate (DHPJA) was used to investigate its effect on stimulating trans-resveratrol (t-R) accumulation and the plant defence responses in Vitis vinifera cv. Kyoho cell suspension cultures for the first time. Results: It demonstrated that DHPJA had superior effects on stilbenoids accumulation over methyl jasmonate (MeJA). The optimal condition was 150 uM DHPJA added on day 15 of cultivation period, with the highest level of t-R accumulation which was increased 1.8-fold and 1.3-fold compared with the control and 150 uM MeJA respectively. DHPJA induced stronger plant defence responses, including oxidative burst and activation of L-phenylalanine ammonia lyase (PAL) than MeJA. H2O2 generation induced by DHPJA played a significant role in enhancing t-R accumulation. Adding a specific inhibitor of H2O2 signalling pathway inhibited DHPJA-induced t-R accumulation, but had no effects on DHPJA-induced other metabolites accumulation, which resulted in regulations of product diversity. Conclusions: This study demonstrated that DHPJA was an efficient elicitor to enhance t-R accumulation by activating stronger oxidative burst, and H2O2 signalling pathway could regulate product diversity in DHPJA-induced V. vinifera cv. Kyoho cell suspension cultures.
Subject(s)
Cyclopentanes/pharmacology , Stilbenes/metabolism , Vitis/metabolism , Cells, Cultured , OxylipinsABSTRACT
Objective To evaluate toxicity and safety of trans-resveratrol (t-RSV). Methods For assays of acute toxicity,genetic toxicity, and sub-chronic toxicity, Ames test, mice bone marrow erythrocyte micronucleus, and mice sperm abnormality were performed. Results In the acute oral toxicity tests, maximum tolerable dose (15 g/kg) in male and female Kunming mice showed no toxicological signs. For 90-d feeding of t-RSV at dosage range of 167-500 mg/(kg·d) in both male and female Sprague-Dawley rats, no noticeable toxicological effects were observed.Conclusion T-RSV has no acute toxicity and no genotoxicity, no harmful effects on the human body at the tested dosage range and thus resveratrol is safe for human consumption.