Pharmacokinetics, tissue distribution and excretion study of trans-resveratrol-3-O-glucoside and its two metabolites in rats

Mei-ying, SU; Dong, Chen; Wan, Jiyun; Mao-jin, Zhou

doi:10.1016/j.phymed.2019.152882

Cited by 22 publications

(21 citation statements)

References 23 publications

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“…Radioactivity indeed was mostly recovered in urine and was very low along the gastrointestinal tract. Consistent with these findings, several other investigations remarked the renal excretion to be the major way of elimination of resveratrol [22,25,26,28,30,42].…”

Section: Physico-chemical and Pharmacokinetic Properties Of Resveratrolsupporting

confidence: 72%

“…Moreover, trans-resveratrol and relative conjugates were found to be distributed mainly in the liver and kidneys, the primary sites of metabolism and excretion, but radioactivity of 14 C-labeled resveratrol was observed also in the oral cavity, stomach and intestines suggesting a "resveratrol reservoir" of these tissues [14,20]. In accordance with previous investigations, Menet et al confirmed, in an animal model, that after both single dose and sustained resveratrol intake, the distribution was higher in kidneys and the liver, whereas recently the pharmacokinetic analysis by Su and colleagues demonstrated that the major distribution of resveratrol, derivatives and metabolites occurred in the gastrointestinal tract after oral intake [21,22]. As mentioned above, resveratrol undergoes rapid and extensive metabolism, and several studies were conducted in order to identify resveratrol metabolites.…”

Section: Physico-chemical and Pharmacokinetic Properties Of Resveratrolsupporting

confidence: 63%

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Resveratrol in Cancer Patients: From Bench to Bedside

Berretta

Bignucolo

Francia

et al. 2020

IJMS

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Resveratrol (3,5, is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.properties of resveratrol are, however, marked by a pharmacokinetic profile and by an unfavorable oral bioavailability, which requires a thorough analysis. To date, to the best of our knowledge, scientific papers and reviews summarizing multiple characteristics of resveratrol, its pharmacokinetic, pharmacodynamic profiles and potential drug interaction in oncology are lacking in literature. Therefore, this review aimed to describe the potential use of resveratrol in cancer management presenting the main biochemical pathways involved, issues and potential uses in cancer patients. Moreover, the involvement of resveratrol in cardioncology, its potential use for risk reduction of myocardial ischemia, myocarditis, cardiac hypertrophy as well as heart failure are also discussed. To endorse this review, we made a comprehensive search on PubMed, Web of Science and SciFinder. The search terms were "resveratrol" combined with "cardioncology" or "cancer" or "drug-food" or "cardiology" or "pharmacokinetic" or "pharmacodynamic". Physico-Chemical and Pharmacokinetic Properties of ResveratrolResveratrol is a low molecular weight phyto-polyphenol of 228 Da that appears as an off-white powder with lipophilic properties (octanol/water partition coefficient, log Kow = 3.1). Its melting point is between 253 and 255 • C, and its solubility in water is very low (3 mg/100 mL) [8]. The ethylene bridge due to a limited degree of freedom generates two geometric isomers: cis-resveratrol and trans-resveratrol ( Figure 1) [5]. These isoforms co-exist in resveratrol extracts even if a greater biological activity and stability are attributed to trans-resveratrol. Comparing to the geometric isomers, the nearly planar structure of trans-resveratrol is less flexible than the non-planar structure of cis-resveratrol, but it possesses a lower repulsive energy that ensures it, albeit small, higher stability. Isomerization of trans-resveratrol to cis-resveratrol occurs via molecule breakdown when trans-resveratrol is exposed to UV radiation at a wavelength of 254 or 366 nm, to high pH conditions or in plants during fermentation processes [5,9]. In analyzing some physical-chemical aspects of resveratrol, Zupancic et al. showed how trans-resveratrol is rapidly degradable in high-pH solutions. In par...

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Section: Physico-chemical and Pharmacokinetic Properties Of Resveratrolsupporting

confidence: 72%

Section: Physico-chemical and Pharmacokinetic Properties Of Resveratrolsupporting

confidence: 63%

Resveratrol in Cancer Patients: From Bench to Bedside

Berretta

Bignucolo

Francia

et al. 2020

IJMS

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“…It is commonly believed that the glucuronidated and sulfated metabolites should be less potent as they are more polar and possess lower bio‐membrane permeability. Evidently, glucuronidated‐RES displayed lower tissue distribution in comparison with plasma, particularly in lipid‐rich organs . Although the exact impacts of RES metabolites on the in vivo pharmacology of RES remain unclear, they could contribute through at least two different mechanisms: i) although RES conjugates have lower activities, as they are at very high abundance, their effective concentrations may still be achievable; ii) the glucuronide(s) and sulfate(s) of RES could serve as a deposit of RES as they can be converted back to RES through reverse metabolism by glucuronidase and sulfatase .…”

Section: Discussionmentioning

confidence: 99%

Biotransformation of Piceatannol, a Dietary Resveratrol Derivative: Promises to Human Health

Dai

Lim

Yeo

et al. 2020

Molecular Nutrition Food Res

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Scope: To evaluate the health-promoting potentials of piceatannol (PIC), a dietary resveratrol derivative, its biotransformation is examined. Methods and results: The biotransformation is tested in human/rat hepatic microsomes and cytosols; its pharmacokinetic profiles are assessed in rats. Although limited phase I metabolism exists in microsomes, PIC is rapidly converted to two pharmacologically active metabolites, namely rhapontigenin (RHA) and isorhapontigenin (ISO) in cytosols. Such biotransformation is completely blocked by entacapone, a well-known catechol-O-methyltransferase (COMT) inhibitor, demonstrating that the O-methylation is mediated by COMT. Moreover, PIC is identified as a substrate inhibitor of COMT, suggesting its potential benefits in Alzheimer's disease. Due to extensive phase II metabolism including glucuronidation, sulfation, and O-methylation, PIC displays rapid clearance and at least4.02% ± 0.61% and 17.70% ± 0.91% of PIC is converted to RHA and ISO, respectively, in rats after intravenous administration. Similarly, PIC serves as an effective precursor of ISO upon oral administration. Conclusion: Since PIC and its metabolites possess pleiotropic health-promoting activities, it has emerged as a promising nutraceutical candidate for further development. This study also reinforces the importance of in vivo testing in nutritional researches as the active metabolite(s) may be absent from the in vitro system.

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“…[106,107] RESV and its metabolites, dihydroresveratrol and piceatannol, enter the bloodstream and the liver, where they are metabolized by its CYP proteins, experiencing second-phase metabolization, which conjugates the compound with glucuronides and sulfates to turn it into more polar molecules to facilitate its glomerular filtration in the kidneys (Figure 3), followed by the excretion of these metabolites through the urine. [105,108] RESV glucuronide conjugation occurs by the action of the uridine diphosphate glucuronosyl transferase (UGT) family, with UGT1A1…”

Section: Neurological Diseasesmentioning

confidence: 99%

“…Trans-RESV-3-O-glucuronide was the major metabolite, and in urine, its quantified percentage was 52.8% (up to 72-hr dose). [108] Under the action of sulfotransferase (SULT) enzymes, RESV undergoes sulfate conjugation, with SULT1A1 (or phenolsulfotransferase) being the most important of them and responsible for its metabolism in various tissues, such as kidney, liver, and brain. [111] and then the metabolites enter the systemic circulation to be absorbed by peripheral tissues, exhibiting their biological effects.…”

Section: Neurological Diseasesmentioning

confidence: 99%

Resveratrol isoforms and conjugates: A review from biosynthesis in plants to elimination from the human body

Riccio

Spósito

Carvalho

et al. 2020

Archiv der Pharmazie

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The natural isomers of resveratrol, cis-and trans-resveratrol, are natural phenolic substances synthetized via the shikimate pathway and found in many sources, including grapes, peanuts, blackberries, pistachios, cacao, cranberries, and jackfruits. They have functional and pharmacological properties such as anticarcinogenic, antidiabetic, anti-inflammatory, and cardioprotective activities. The aim of this article is to review the data published on resveratrol and its isomers, and their biosynthesis in plants, food sources, health and toxic effects, and the excretion of their metabolites. Due to its contribution to the promotion of human health, it is convenient to gather more knowledge about its functional properties, food sources, and the interactions with the human body during the processes of eating, digestion, absorption, biotransformation, and excretion, to combine this information to improve the understanding of these substances.

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Pharmacokinetics, tissue distribution and excretion study of trans-resveratrol-3-O-glucoside and its two metabolites in rats

Cited by 22 publications

References 23 publications

Resveratrol in Cancer Patients: From Bench to Bedside

Resveratrol in Cancer Patients: From Bench to Bedside

Biotransformation of Piceatannol, a Dietary Resveratrol Derivative: Promises to Human Health

Resveratrol isoforms and conjugates: A review from biosynthesis in plants to elimination from the human body

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