Maturity-dependent enzyme inhibition in grape seeds: Urease, α-amylase, and lipase inhibitory activities with lipase...

This study investigated the enzyme inhibitory, antimicrobial, and molecular docking properties of grape seed extracts obtained from three Algerian grape cultivars-Sabel, Red Globe, and Cardinal-harvested at different ripening stages. The extracts demonstrated strong inhibitory activity against urease, α-amylase, and lipase, with variability depending on both cultivar and maturation stage. Cardinal seeds displayed the most potent urease inhibition ((IC₅₀ = 3.37 µg/mL) at the BV stage, surpassing the reference thiourea (7.27 ± 1.04 µg/mL), whereas α-amylase inhibition was consistently higher than the commercial inhibitor acarbose with the best activity recorded in RG at repining stage (IC₅₀ = 31.94 µg/mL). Lipase inhibition was markedly enhanced at the late ripening stage for Sabel and Cardinal, highlighting maturation as a critical determinant of bioactivity. Docking simulations revealed that catechin, luteolin, and resveratrol established stable interactions with catalytic residues of pancreatic lipase, supporting the in vitro findings. ADME/Tox predictions confirmed favorable pharmacokinetic properties and low toxicity for most compounds. Antimicrobial assays further demonstrated cultivar-dependent activity against multidrug-resistant Escherichia coli, Candida albicans, and Aspergillus niger, with Cardinal and Red Globe showing the strongest effects with the highest inhibition zones up to 19 mm against multidrug-resistant E. coli. Together, these results highlight grape seeds as a significant reservoir of bioactive substances with possible uses in managing metabolic disorders, infections, and obesity.