Unlocking the Ilex guayusa Potential: Volatile Composition, Antioxidant, Antidiabetic, and Hemolytic Activities, with In Silico Molecular Docking and ADMET Analysis of Hydroethanolic Extracts

This work studies the underexplored potential of Ilex guayusa and demonstrates the influence of geographical (locations: A, B, C) and ontogenetic (young: 0; old: 2) factors on its biochemical profile. The total phenolic content (TPC) was consistently higher than the total flavonoid content (TFC) in all samples, with the highest values for site B: B2 for TPC (77.91 μg GAE/mg extract) and B0 for TFC (6.77 μg QE/mg extract). GC–MS identified 29 metabolites, and clustering analysis grouped samples B and C as rich in phenols and flavonoids, while site A was richer in alcohols, aldehydes, and hydrocarbons. Antioxidant potential was demonstrated, with B2 being the most active in ABTS (TEAC value of 0.3885 (mg/g dw)), whereas A2 and C2 showed the strongest activity in DPPH (0.0968 and 0.1850 (mg/g dw), respectively). No sample exhibited hemolysis and α-amylase inhibition; however, α-glucosidase inhibition was observed with the best activity for B0 (IC50 = 68.05 µg/mL). Molecular docking, ADME, and correlation analyses indicated that B0 had the highest TFC, DPPH, and α-glucosidase inhibition values, while B2 showed the highest TPC and ABTS activity. Overall, the promising antioxidant and hypoglycemic activity combined with low toxicity highlights and expands the therapeutic and applicative potential of the species.