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A B S T R A C TFlavan-3-ols and their oligomeric forms, proanthocyanidins (PAs), are poorly absorbed in the small intestine and reach the colon where gut bacteria enzymes can hydrolyse them to produce small molecular metabolites, which can reach systemic circulation. However, the microbial metabolism of flavanols has been poorly described in vivo. The aim of this study was to determine the colonic biotransformation pathway and the plasma temporal appearance of grape seed flavanols colonic metabolites in rats. Rat plasma colonic metabolites were analysed by HPLC-MS/MS at 2, 7, 24 and 48 h after 1000 mg/kg of a grape seed PA extract (GSPE) administration. Results indicated that non-metabolised flavanols have peak plasma concentrations 2 h after GSPE administration, whereas the colonic metabolites appeared in plasma later, indicating their gradual colonic biotransformation as valerolactone > phenylpropionic acids ≈ phenylacetic acids > benzoic acids. This study shows how flavanols are biotransformed by gut bacteria in rats over time, facilitating potential bioactive compound identification for particular health effects.

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Cardiovascular disease (CVD) and related pathologies are the leading cause of death worldwide. Fruits and vegetables are known to improve CVD, an effect that has been associated with flavonoid intake. The aim of this study was to simultaneously evaluate the acute effect of a low molecular grape seed proanthocyanidin extract (LM-GSPE) on two of the main risk factors of CVD, high blood pressure (BP) and dyslipidaemia, using high-fat diet-fed rats. Therefore, male Wistar rats that were cafeteria diet fed for 10 weeks were administered with 375 mg/kg of body weight of LM-GSPE, and the BP as well as plasmatic and hepatic parameters were determined at 6 h post-administration. The BP and plasmatic and hepatic lipid were decreased 6 h after the LM-GSPE administration. Moreover, the liver lipid peroxidation products decreased after the LM-GSPE treatment, indicating a reduction in oxidative stress. However, hepatic-reduced glutathione or plasma angiotensin converting enzyme activity was not altered by the LM-GSPE. In conclusion, grape proanthocyanidins is able to simultaneously reduce more than one risk factor for CVD by decreasing the BP and improving hypertriglyceridaemia at least in part due to an improvement in oxidative stress. These results open up the possibility of using grape proanthocyanidins in functional foods for CVD improvement.