Viniferin is a phenolic compound belonging to the group of stilbenoids. In particular, ε-viniferin is a dimer of resveratrol, found in many plant genders, among which grapes (Vitis vinifera) are a primary source. Due to the fact that ε-viniferin is mainly present in the woody parts of plants, their use as a source of this bioactive compound is a very interesting issue in a circular economy. Both, in vitro studies carried out in pre-adipocytes and mature adipocytes and in vivo studies addressed in mice show that ε-viniferin is able to reduce fat accumulation. Moreover, it prevents the development of some obesity co-morbidities, such as type 2 diabetes, dyslipidemias, hypertension and fatty liver. ε-viniferin can be absorbed orally, but it shows a very low bioavailability. In this scenario, further research on animal models is needed to confirm the effects reported in a great number of studies; to determine which metabolites are involved, including the main one responsible for the biological effects observed and the mechanisms that justify these effects. In a further phase, human studies should be addressed in order to use ε-viniferin as a new tool for obesity management, as a nutraceutical or to be included in functional foods.

Onion-type multi-lamellar liposomes (MLLs), composed of a mixture of phosphatidylcholine and Tween 80, were analyzed for their ability to encapsulate ε-Viniferin (εVin), a resveratrol dimer. Their encapsulation efficiency (EE) was measured by UV-VIS spectroscopy using three different separation methods—ultracentrifugation, size exclusion chromatography, and a more original and advantageous one, based on adsorption filtration. The adsorption filtration method consists indeed of using syringe filters to retain the molecule of interest, and not the liposomes as usually performed. The process is rapid (less than 10 min), easy to handle, and inexpensive in terms of sample amount (around 2 mg of liposomes) and equipment (one syringe filter is required). Whatever the separation method, a similar EE value was determined, validating the proposed method. A total of 80% ± 4% of εVin was found to be encapsulated leading to a 6.1% payload, roughly twice those reported for resveratrol-loaded liposomes. Finally, the release kinetics of εVin from MLLs was followed for a 77 day period, demonstrating a slow release of the polyphenol.

Genotoxic data of substances that could be used as food additives are required by the European Food Safety Authority. In this sense, the use of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99), due to its antioxidant and antibacterial activities, has been proposed as an alternative to sulfur dioxide in wine. The aim of this work was to study, for the first time, the in vivo genotoxic effects produced in rats orally exposed to 90, 180, or 360 mg ST-99/kg body weight at 0, 24, and 45 h. The combination of micronucleus assay in bone marrow (OECD 474) and standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach, liver, and blood of exposed animals. The ST-99 revealed no in vivo genotoxicity. These results were corroborated by analytical studies that confirm the presence of stilbenes and their metabolites in plasma and tissues. Moreover, to complete these findings, a histopathological study was performed under light microscopy in liver and stomach showing only slight modifications in both organs at the highest concentration used. The present work confirms that this extract is not genotoxic presenting a good profile for its potential application as a preservative in the wine industry.

Trans-ε-viniferin (εVin) is a resveratrol dimer exhibiting promising biological activities for human health. Its bioavailability being low, the development of encapsulation methods would be used to overcome this issue. The aim of this study was to measure the consequences of the encapsulation of εVin in multilamellar liposomes on its pharmacokinetic parameters, metabolism and tissue distribution in rats. After oral administration of εVin (20 mg/kg body weight), either as free or encapsulated forms, plasmas were sequentially collected (from 0 to 4 h) as well as liver, kidneys and adipose tissues (4 h after administration) and analyzed by LC-HRMS. The glucuronide metabolites (εVG) were also produced by hemisynthesis for their quantification in plasma and tissues. The encapsulation process did not significantly modify the pharmacokinetic parameters of εVin itself. However, a significant increase of the T_1/2 was noticed for εVG after administration of the encapsulated form as compared to the free form. An accumulation of εVin and εVG in adipose tissues was noticed, and interestingly a significant increase of the latter in the mesenteric one after administration of the encapsulated form was highlighted. Since adipose tissues could represent storage depots, and encapsulation allows for prolonging the exposure time of glucuronide metabolites in the organism, this could be of interest to promote their potential biological activities.

Trans-ε-viniferin, a resveratrol dimer found mainly in grapevine wood, has shown protective capacities against hepatic steatosis in vivo. Nevertheless, this compound is very poorly bioavailable. Thus, the aim of the present study is to determine the potential anti-steatotic properties of 1 and 10 µM of trans-ε-viniferin and its four glucuronide metabolites in AML-12 cells treated with palmitic acid as an in vitro model of hepatic steatosis. The effect of the molecules in cell viability and triglyceride accumulation, and the underlying mechanisms of action by Real-Time PCR and Western Blot were analysed, as well as the quantification of trans-ε-viniferin and the identified bioactive metabolite inside cells and their incubation media. Interestingly, we were able to determine the triglyceride-lowering property of one of the glucuronides (trans-ε-viniferin-2-glucuronide), which acts on de novo lipogenesis, fatty acid uptake and triglyceride assembly. The glucuronides of trans-ε-viniferin would therefore be partly responsible for the in vivo observed anti-steatotic properties of the parent compound.