Red Grape Pomace as a Valuable Source of Biomolecules With Inhibitory Effect on Pro-Inflammatory and Metabolic Syndrome-Associated Enzymes: Eco-Friendly Extraction and Mechanism of Inhibition.

In this study, the interaction models between an extract of red grape pomace obtained by extraction with eutectic solvents and three enzymes, responsible for pro-inflammatory (lipoxygenase) and metabolic syndrome responses (α-amylase and α-glucosidase), were systematically investigated through experiments and computational simulations. The chromatographic analysis allowed the identification of thirty-two polyphenolic compounds in the extract, predominantly phenolic acids (73%), with a total polyphenol content of 575.58 mg/kg. The main identified compounds were vanillic acid, azelaic acid, chlorogenic acid, suberic acid, abietic acid, phlorizin, polydatin, and t-resveratrol. SwissADME and ProTox-3.0 bioinformatic tools were employed to assess the absorption, distribution, metabolism, and excretion, highlighting that 23.23% of the identified compounds may exert good oral bioavailability in humans and neuroprotective or cognitive-enhancing effects within the central nervous system. A high inhibition rate of 99% for amylase and glucosidase and 82% for lipoxygenase was suggested. The thermodynamic analysis suggested that hydrogen bonding, van der Waals, and hydrophobic forces primarily drove the interactions. The molecular docking results revealed details on the potential mechanisms involved in the inhibition of the metabolic syndrome-associated enzymes exerted by the phenolic compounds from red grape extract. Different phenolic compounds were identified to attach to the active site of the enzymes, interfering with their activity. The anti-diabetic activity might be assigned to vanillic acid and suberic acid, which bind to α-amylase and α-glucosidase respectively, whereas suberic acid and resveratrol appeared to be responsible for the direct inhibitory mechanism of lipoxygenase.