Distribution of [H]trans-resveratrol in rat tissues following oral administration

El-Mohsen, Manal Abd; Bayele, Henry K.; Kuhnle, Gunter; Gibson, Glenn; Debnam, ES; Srai, Surjit Kaila; Rice‐Evans, Catherine; Spencer, Jeremy P. E.

doi:10.1079/bjn20061810

Cited by 118 publications

(81 citation statements)

References 23 publications

(30 reference statements)

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“…RES and derived metabolites were already extensively distributed in the pig body 6 h after RES administation with the highest amounts detected in the K and the Lv. The main compound detected in pig Br was RES (17) in accordance with the previous studies on rats [15]. This is of interest in relation to the modulation of several blood flow variables in humans 45 min after RES (500 mg) intake [51] and indicates that RES itself could be the bioactive molecule in Br.…”

Section: Discussionsupporting

confidence: 83%

Metabolites and tissue distribution of resveratrol in the pig

Azorín-Ortuño

Yáñez‐Gascón

Vallejo

et al. 2011

Molecular Nutrition Food Res

121

123

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Scope: trans‐Resveratrol (RES) and/(or) its metabolites exert many effects in vivo. Our aim was to study the metabolism and tissue distribution of RES using the pig, a mammal physiologically close to humans.Methods and results: Forty‐seven tissues, organs and fluids were analyzed 6 h after intragastric RES administration (5.9 mg/kg body weight) using HPLC‐MS/MS. Twelve RES and seven dihydroresveratrol (DH‐RES) metabolites were detected. DH‐RES was the main metabolite in cecum, colon and rectum, whereas RES‐3‐O‐glucuronide was the most abundant one in fluids and organs. Approximately 74.5% of the total RES administered was recovered in the form of RES, DH‐RES and derived metabolites (65.1% along the gastrointestinal tract, 7.7% in urine, 1.2% in bile and 0.5% in organs). We report here, for the first time, the occurrence of RES ribosyl‐sulfate derivative, DH‐RES diglucuronide, DH‐RES sulfoglucuronide and DH‐RES disulfate as well as the metabolic profile of RES and DH‐RES in the aorta, lymph, lymph node, ovaries, uterus, cerebellum, pancreas, urinary bladder tissue, fat and muscle.Conclusion: This study contributes to the clarification of the metabolism and tissue distribution of RES and could help to further understand the mechanisms underlying its effects.

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Section: Discussionsupporting

confidence: 83%

Metabolites and tissue distribution of resveratrol in the pig

Azorín-Ortuño

Yáñez‐Gascón

Vallejo

et al. 2011

Molecular Nutrition Food Res

121

123

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“…However, resveratrol aglycon could not be detected (data not shown). Several polyphenols are accumulated within human cells in a tissue-specific manner (29,30). Like resveratrol, quercetin also acts as an anti-inflammatory polyphenol in cardiovascular diseases (31,32).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Inhibits Hypoxia-Inducible Factor-1^|^alpha;-Mediated Androgen Receptor Signaling and Represses Tumor Progression in Castration-Resistant Prostate Cancer

Mitani

Harada

Tanimori

et al. 2014

J Nutr Sci Vitaminol

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Summary Androgen-dependent prostate cancer inevitably progresses to incurable castration-resistant prostate cancer (CRPC) after androgen deprivation therapy. Because castration-induced hypoxia-inducible factor (HIF)-1a enhances the transcriptional activity of androgen receptor (AR) at low androgen levels mimicking the castration-resistant stage, HIF-1a is expected to be a promising target for suppression of growth of CRPC. We investigated the effect of resveratrol (3,4′,5-trihydroxy-trans-stilbene) on the growth of human prostate cancer LNCaP xenografts in castrated male BALB/cSlc-nu/nu mice (5 wk old). The mice were administered a control diet or a resveratrol diet (4 g/kg diet) for 40 d. The resveratrol diet significantly suppressed tumor growth compared to the control diet. In LNCaP xenografts, dietary resveratrol decreased the protein level of HIF-1a, but not the AR coactivator b-catenin, and reduced the mRNA levels of androgen-responsive genes. In the control group, b-catenin was predominantly localized in the nucleus with HIF-1a in LNCaP xenografts, whereas dietary resveratrol inhibited the nuclear accumulation of b-catenin. In hypoxic LNCaP cells at a low androgen level mimicking the castration-resistant stage, hypoxia-induced nuclear accumulation of b-catenin was inhibited by resveratrol. Furthermore, resveratrol repressed the expression level of HIF-1a even in the presence of a proteasome inhibitor and suppressed hypoxia-enhanced AR transactivation. These results indicate that dietary resveratrol represses nuclear localization of b-catenin by decreasing the HIF-1a expression, perhaps in a proteasome-independent manner, and inhibits b-catenin-mediated AR signaling; this contributes to suppression of tumor growth of CRPC.

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“…Reporting of plasma resveratrol measurements has been inconsistent, with researchers employing a variety of analytical chemistry techniques, and with some reporting concentrations of resveratrol and its metabolites separately [29] and others reporting combined measurements [35]. Animal models have suggested that metabolites of resveratrol may be converted back into resveratrol at the tissue level, although this has not been rigorously demonstrated [29,42]. Finally, there is limited and sometimes conflicting information available from basic science research regarding the plasma concentrations necessary for a given physiological effect.…”

Section: Limitations To Bioavailability Researchmentioning

confidence: 99%

Resveratrol and health – A comprehensive review of human clinical trials

Smoliga

Baur

Hausenblas

2011

Molecular Nutrition Food Res

488

307

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In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti-aging, anti-carcinogenic, anti-inflammatory, and anti-oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well-tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials.

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Distribution of [H]trans-resveratrol in rat tissues following oral administration

Cited by 118 publications

References 23 publications

Metabolites and tissue distribution of resveratrol in the pig

Metabolites and tissue distribution of resveratrol in the pig

Resveratrol Inhibits Hypoxia-Inducible Factor-1^|^alpha;-Mediated Androgen Receptor Signaling and Represses Tumor Progression in Castration-Resistant Prostate Cancer

Resveratrol and health – A comprehensive review of human clinical trials

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