Simultaneous quantification of trans-resveratrol and its sulfate and glucuronide metabolites in rat tissues by stable isotope-dilution UPLC–MS/MS analysis

Lou, Bih-Show; Wu, Po Kuei; Hou, Chun-Wei; Cheng, Fu-yin; Chen, Jan‐Kan

doi:10.1016/j.jpba.2014.01.039

Cited by 24 publications

(11 citation statements)

References 29 publications

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“…Lou et al analyzed the distribution of Resv and its metabolites in rats after intravenous administration of Resv at 20 mg·Resv/kg b.w. [ 74 ]. Total Resv and metabolite concentration over time was found to have the highest concentration in the kidneys, followed by the plasma, heart, liver, and brain.…”

Section: In Vivo Exposure To Resveratrol: What mentioning

confidence: 99%

Challenges in Analyzing the Biological Effects of Resveratrol

Erdoğan

Vang

2016

Nutrients

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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 biological effects. Extrapolating the biological effects of dietary compounds from in vitro and in vivo animal experiments to humans may lead to over- or under-estimation of the effect and role of these compounds. The present paper will discuss a few of these challenges and suggest directions for future 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.

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Section: In Vivo Exposure To Resveratrol: What mentioning

confidence: 99%

Challenges in Analyzing the Biological Effects of Resveratrol

Erdoğan

Vang

2016

Nutrients

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“…Both conjugations occur preferentially at the 3-OH group compared to the 4′-OH group [ 15 , 16 ]. In rats, the main metabolites are resveratrol-3- O -glucuronide and resveratrol-3- O -sulfate [ 17 ], whereas in human the 3- O -sulfate form is the major metabolite and the glucuronides are found only in small amounts [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Glucuronidation and Sulfation of ε-Viniferin, a Resveratrol Dimer, in Humans and Rats

et al. 2017

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ε-Viniferin is a resveratrol dimer that possesses antioxidant or anti-inflammatory activities. However little is known about the metabolism of this oligostilbene. This study was thus undertaken as a first approach to identify and characterize the metabolites of ε-viniferin and to describe the kinetic profile of their appearance in humans and rats. The glucuronides and sulfates of ε-viniferin were first obtained by chemical hemi-synthesis and were fully characterized by UPLC-MS and NMR spectroscopy. Then, ε-viniferin was incubated with human or rat S9 liver fractions that led to the formation of four glucuronoconjugates and four sulfoconjugates. In both species, ε-viniferin was subjected to an intense metabolism as 70 to 80% of the molecule was converted to glucuronides and sulfates. In humans, the hepatic clearance of ε-viniferin (Vmax/Km) for glucuronidation and sulfation were 4.98 and 6.35 µL/min/mg protein, respectively, whereas, in rats, the hepatic clearance for glucuronidation was 20.08 vs. 2.59 µL/min/mg protein for sulfation. In humans, three major metabolites were observed: two glucuronides and one sulfate. By contrast, only one major glucuronide was observed in rats. This strong hepatic clearance of ε-viniferin in human and rat could explain its poor bioavailability and could help to characterize its active metabolites.

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“…Indeed, the modifications just mentioned have been long recognized and studied for representative members of this huge family of natural compounds, including resveratrol, which is of specific interest here. Rapid glucuronidation and sulfation in enterocytes, hepatocytes, and other cells (e.g., [14][15][16][17][18][19][20][21]) and re-export to the intestinal lumen by MDR proteins [15,22,23], or possibly OATPs [24], are thought to limit the potential impact of this celebrated "natural drug" in vivo. This is a pity, given the pleiotropic effects this dietary compound is reported to have in important pathophysiological respects (for recent reviews see, e.g., [25][26][27][28][29][30]).…”

Section: Introductionmentioning

confidence: 99%

N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

et al. 2015

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Abstract:Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH3-[OCH2CH2]n-) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.

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Simultaneous quantification of trans-resveratrol and its sulfate and glucuronide metabolites in rat tissues by stable isotope-dilution UPLC–MS/MS analysis

Cited by 24 publications

References 29 publications

Challenges in Analyzing the Biological Effects of Resveratrol

Challenges in Analyzing the Biological Effects of Resveratrol

In Vitro Glucuronidation and Sulfation of ε-Viniferin, a Resveratrol Dimer, in Humans and Rats

N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

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