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Resveratrol is a well-known wine constituent. Its concentration can vary according to the cultivar choice and the winemaking process. Due to its phenolic structure, resveratrol could be transformed under high temperature or oxidative conditions, leading to the formation of various derivatives including oligomers. Hence, the goal of this study is to investigate the presence of these derivatives in wine. In the first stage, hemisynthesis of oligomeric stilbenes was achieved from resveratrol in ethanol by oxidative coupling using metals. Four de novo synthetized resveratrol derivatives were identified by MS and NMR spectroscopy including two new molecules, oxistilbenin F and oxistilbenin G. In the second stage, analysis of red wine after heat treatment by LC-MS confirmed the presence of some of these compounds in wine. Finally, the anti-inflammatory effects of the compounds were evaluated by studying their ability to prevent lipopolysaccharide (LPS)-induced upregulation of nitric oxide (NO) and reactive oxygen species (ROS) production in RAW 264.7 macrophage cell line., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The control of oxidative stress with natural active substances could limit the development of numerous pathologies. Our objective was to study the antiradical effects of resveratrol (RSV), ε-viniferin (VNF), and vitisin B (VB) alone or in combination, and those of a standardized stilbene-enriched vine extract (SSVE). In the DPPH-, FRAP-, and NO-scavenging assays, RSV presented the highest activity with an IC50 of 81.92 ± 9.17, 13.36 ± 0.91, and 200.68 ± 15.40 µM, respectively. All binary combinations resulted in additive interactions in the DPPH- and NO-scavenging assays. In the FRAP assay, a synergic interaction for RSV + VNF, an additive for VNF + VB, and an antagonistic for RSV + VB were observed. The ternary combination of RSV + VNF + VB elicited an additive interaction in the DPPH assay and a synergic interaction in the FRAP- and NO-scavenging assays. There was no significant difference between the antioxidant activity of the SSVE and that of the combination of RSV + VNF. In conclusion, RSV presented the highest effects, followed by VNF and VB. The interactions revealed additive or synergistic effects, depending on the combination of the stilbenes and assay. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most frequent cancer worldwide, accounts for about 10% of the total cancer cases, and ranks as the second cause of death by cancer. CRC is more prevalent in developed countries in close causal relation with occidental diets. Due to anatomy, the diet has a strong impact on CRC. High contents in meat are acknowledged risk factors whereas a diet rich in fruits and vegetables is an established CRC protective factor. Fruits and vegetables contain numerous Bioactive Food Components (BFCs), physiologically active food compounds, beneficial on health. Preventive and therapeutic benefits of BFCs in cancer have increasingly been reported over the past 20 years. BFCs show both chemopreventive and anti-tumor properties in CRC but more interestingly, abundant research describes BFCs as enhancers of conventional cancer treatments. Despite these promising results, their clinical transferability is slowed down by bioavailability interrogations and their poorly understood hormetic effect. In this review, we would like to reposition BFCs as well-fitted for applications in CRC. We provide a synthetic overview of trustworthy BFC applications in CRC, with a special highlight on combinatory approaches and conventional cancer treatment potentiation strategies. [ABSTRACT FROM AUTHOR]

Stilbenes, of which resveratrol is the most studied, were described as antioxidant and anti-inflammatory molecules. Presumably, other stilbenes have similar biological properties, but the evidence is poorly documented. Therefore, 20 stilbenes from resveratrol monomers to tetramers were screened as anti-inflammatory and antioxidant agents in a cellular model of LPS-stimulated murine macrophages. Piceatannol (monomer), ϵ-viniferin and δ-viniferin (dimers), hopeaphenol and isohopeaphenol (tetramers) were the most powerful compounds that inhibited NO and ROS generation upon LPS exposure. Among these compounds, hopeaphenol (5-10 µM) showed the highest efficiency. Nevertheless, ϵ-viniferin was the most powerful to inhibit TNF-α release whereas isohopeaphenol was the greatest to reduce IL-1β upon LPS stimulation. Thus, this work provided evidence that the chemical structure of stilbenes is highly relevant to the behavior of their activities. These results will allow the selection of potential bioactive stilbenes to develop further studies to elucidate their molecular mechanism of action. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Stilbenes (resveratrol derivatives) are a polyphenol class encountered in a large number of specimens in the vegetal realm. They adopt a variety of structures based on their building block: resveratrol. As the most widely studied stilbene to date, resveratrol has shown multiple beneficial effects on multiple diseases and on neurodegenerative diseases. Except for resveratrol, however, the biological activities of stilbenes have received far less attention, even though some of them have shown promising effects on neurodegenerative disease. This review covers the chemistry of stilbenes and offers a wide insight into their neuroprotective effects. [ABSTRACT FROM AUTHOR]

Some red wine polyphenols exert nitric oxide (NO)-dependent relaxation in systemic arteries, following activation of endothelial NO synthase (eNOS). In this study, the effect of red wine polyphenols was determined in rat intrapulmonary arteries, and the effect of some of these compounds was compared with the responses obtained in rat aorta. In pulmonary arteries, red wine polyphenolic extract (> 300 μg/mL) exerted relaxation that was not inhibited by the NOS inhibitor N ω-nitro-l-arginine methylester (l-NAME) or endothelium removal. Among the several fractions obtained from the extract, the one enriched with anthocyanins was less active than fractions containing non-anthocyanins. Among the latter, the most active for relaxing pulmonary arteries was the one enriched in the stilbene derivative trans-resveratrol (relaxation for concentration >10 μg/mL). Trans-piceid, the glucoside derivative of trans-resveratrol, was almost inactive. Trans-resveratrol-induced relaxation, as well as relaxation to the anthocyanin delphinidin, wasl-NAME-insensitive in pulmonary arteries. In aorta, trans-resveratrol and trans-piceid exerted similar effects to those in pulmonary arteries that were also not inhibited byl-NAME. However, red wine polyphenolic extract and delphinidin induced relaxation of aorta at much lower concentrations (about 10 μg/mL) than in pulmonary arteries, and their effects were inhibited byl-NAME. These data show differences between small intrapulmonary arteries and systemic conductance arteries in their responses to red wine polyphenols, the major difference being that the relaxant effect of these compounds is not blunted by NOS inhibitor in pulmonary arteries. They suggest that red wine polyphenols act directly on smooth muscle to promote pulmonary artery relaxation. [ABSTRACT FROM AUTHOR]

Background/Aims: Glucuronidation of cis- and trans-resveratrol (3,5,4’-trihydroxy-trans-stilbene), which is a naturally occurring phytoalexin known to exert a number of beneficial health effects, was investigated in rat brain, cultured astrocytes and olfactory mucosa. Methods: The isomers were incubated with tissue homogenates, microsomes, or rat liver recombinant UDP-glucuronosyltransferases in the presence of UDP-glucuronic acid. The glucuronides were separated by HPLC and quantitated. Astrocytes were exposed to lipopolysaccharide to promote inflammatory conditions. Results: All tissues were able to form resveratrol glucuronides although at a lower extent, when compared to the liver. The reaction was stereo- and regioselective. In brain tissue, trans-resveratrol 3-O-glucuronide was mainly formed, whereas the cis-isomer was glucuronidated at a lower rate on that position. No 4’-O-glucuronide was detected in brain. In olfactory mucosa homogenates, the cis 3-O-glucuronide was mainly formed, whereas the trans-isomer was glucuronidated only on the 3-position. In astrocytes, 3-O-glucuronides of the cis- and trans-resveratrol were only detected. The rat recombinant UGT1A6 and UGT2B1 isoforms were able to glucuronidate cis- and trans-resveratrol. Finally, in inflammatory conditions, trans-resveratrol glucuronidation was enhanced in astrocytes. Conclusion: Brain tissues are effective in the glucuronidation of resveratrol isomers. This metabolism pathway is likely to modulate the concentration of these biologically active substances. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Numerous epidemiological and animal studies have shown that consumption of red wine is related to reduced incidence of cardiovascular diseases and cancer. Trans-resveratrol (3, 5, 4′-trihydroxystilbene), a phenolic compound present in wine, has been reported to have a potential cancer chemopreventive activity. Moreover, it may exert a protective effect against atherogenesis through its antioxidant properties. Trans-piceid (3-ß glucoside of trans-resveratrol) is present to a greater extent than its aglycone in red wine, but hydrolysis of this glycosylated derivative can occur in small intestine and liver, which would enhance the amount of the biological active trans-resveratrol. The present study aimed to investigate the rate of transepithelial transport of trans-piceid using human intestinal Caco-2 cell monolayers and metabolism of this compound during its absorption across the small intestine. The transport of trans-piceid was evaluated in the human epithelial cell line Caco-2, which possesses enterocyte-like properties in vitro. For transepithelial experiments, confluent monolayers of Caco-2 cells were grown on Transwell® inserts. For metabolic studies, we used both Caco-2 cells seeded on 6-well plates and rat small intestine cell-free extracts. The time course of apical (AP) to basolateral (BL) transport of trans-piceid showed that the favorable apparent permeability coefficient (Papp) declined rapidly during the 6 h of the experiment. This observation could be correlated with the appearance of metabolites. After incubation of Caco-2 cells with trans-piceid, trans-resveratrol was detected on both AP and BL sides. By using protein extracts obtained from rat, we conclude that the Lactase Phlorizin Hydrolase (LPH) and Cytosolic-ß-Glucosidase (CBG) are involved in the hydrolysis of trans-piceid. Furthermore, we show that after deglycosylation, the resulting aglycone is metabolized in trans-resveratrol-3- O-ß-glucuronide and to a lesser extent in trans-resveratrol-4′- O-ß-glucuronide, and that UGT1A1 is mainly involved in this metabolism. This study demonstrates that the transepithelial transport of trans-piceid occurs at a high rate and that the compound is deglycosylated in trans-resveratrol. There are two possible pathways by which trans-piceid is hydrolyzed in the intestine. The first is a cleavage by the CBG, after passing the brush-border membrane by SGLT1. The second is deglycosylation on the luminal side of the epithelium by the membrane-bound enzyme LPH, followed by passive diffusion of the released aglycone, which is further metabolized inside the cells into two glucuronoconjugates. [ABSTRACT FROM AUTHOR]

Steatosis is characterized primarily by excessive lipid accumulation in the form of triglycerides in the liver. Although resveratrol shows a low bioavailability, it has significant positive effects on steatosis. The aim of this study was to analyze whether some phase II and microbial resveratrol metabolites (trans-resveratrol-4′-O-glucuronide (R-4G); trans-resveratrol-3-O-glucuronide (R-3G); trans-resveratrol-3-O-sulfate (R-S) and dihydro-resveratrol (DH-R) were effective in reducing hepatocyte fat accumulation. An in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10, or 25 µM resveratrol or its metabolites. Triglycerides and cell viability were assessed using commercial kits. Protein expression of enzymes and transporters involved in triglyceride metabolism were analyzed by western blot. We show for the first time that resveratrol and all the tested metabolites, at 1 µM, partially prevented lipid accumulation induced by the saturated fatty acid PA in AML12 hepatocytes. This effect was mainly due to the inhibition of de novo lipogenesis. This demonstrates that the low bioavailability of resveratrol is not as big a problem as it was thought to be, because resveratrol metabolites contribute to the delipidating effects of the parent compound. [ABSTRACT FROM AUTHOR]

Abstract: Abnormal β-amyloid peptide accumulation and aggregation is considered to be responsible for the formation and cerebral deposition of senile plaques in the brains of patients with Alzheimer’s disease (AD). Inhibition of the formation of β-amyloid (Aβ) fibrils would be an attractive therapeutic target for the treatment of AD. Resveratrol and its derivatives exhibit a broad range of pharmacological properties such as protection against cardiovascular diseases and cancers, as well as promoting antiaging effects. We reported previously that ε-viniferin glucoside (VG), a resveratrol-derived dimer, strongly inhibits Aβ (25-35) fibril formation in vitro. In this study, we investigated the effects of VG on the aggregation of the full-length peptides (Aβ (1-40) and Aβ (1-42)) and on the β-amyloid-induced toxicity in PC12 cells. VG inhibited Aβ cytotoxicity and the non-covalent complex between VG and Aβ was observed by electrospray ionization mass spectrometry. [Copyright &y& Elsevier]