Abstract

Vitis vinifera (grape) contains various compounds with acknowledged phytochemical and pharmacological properties. Among the different parts of the plant, pomace is of particular interest as a winemaking industry by-product. A characterization of the water extract from grape pomace from Montepulciano d’Abruzzo variety (Villamagna doc) was conducted, and the bioactive phenolic compounds were quantified through HPLC-DAD-MS analysis. HypoE22, a hypothalamic cell line, was challenged with an oxidative stimulus and exposed to different concentrations (1 µg/mL−1 mg/mL) of the pomace extract for 24, 48, and 72 h. In the same conditions, cells were exposed to the sole catechin, in a concentration range (5–500 ng/mL) consistent with the catechin level in the extract. Cell proliferation was investigated by MTT assay, dopamine release through HPLC-EC method, PGE2 amount by an ELISA kit, and expressions of neurotrophin brain-derived neurotrophic factor (BDNF) and of cyclooxygenase-2 (COX-2) by RT-PCR. The extract reverted the cytotoxicity exerted by the oxidative stimulus at all the experimental times in a dose-dependent manner, whereas the catechin was able to revert the oxidative stress-induced depletion of dopamine 48 h and 72 h after the stimulus. The extract and the catechin were also effective in preventing the downregulation of BDNF and the concomitant upregulation of COX-2 gene expression. In accordance, PGE2 release was augmented by the oxidative stress conditions and reverted by the administration of the water extract from grace pomace and catechin, which were equally effective. These results suggest that the neuroprotection induced by the extract could be ascribed, albeit partially, to its catechin content.

Highlights

  • Grape (Vitis vinifera) worldwide production was estimated to be more than 79 million tons in 2018 according to the Food and Agriculture Organization (FAO—United Nations) [1], and Italy is one of the leading wine-producing countries with numerous varieties of both red and white wines [2]

  • Different studies suggest the capability of these compounds to cross the blood—brain barrier [27,28,29], which makes the evaluation of neuroprotective effects of extracts containing significant amounts of catechins sensible, as in the case of grape pomace

  • After the evaluation of potential eco-toxicity, the water extract of grape pomace was administered to the hypothalamic cell line Hypo E22, and bio-pharmacological assays were conducted in order to focus on the neuroprotective effects of this extract

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Summary

Introduction

Grape (Vitis vinifera) worldwide production was estimated to be more than 79 million tons in 2018 according to the Food and Agriculture Organization (FAO—United Nations) [1], and Italy is one of the leading wine-producing countries with numerous varieties of both red and white wines [2]. Grape pomace is a biodegradable solid by-product of the winemaking process obtained after mechanical press or fermentation and encompassing peels (skin), seeds, and some parts of the stem [3]. Grape pomace contains significant amounts of substances that can be considered beneficial to human health [4]. It mainly consists of dietary fibers that are present in high levels (up to 85% depending upon the grape variety) and polyphenolic compounds that mainly (about 70%) remain in pomace after the winemaking process [5]. Besides influencing wine quality and properties [6], phenols have potential beneficial effects towards human health. They possess antioxidant, antiviral, antimicrobial, and anti-inflammatory properties which vary with the variety of grapes [7]

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