Journal of Food Science, cilt.91, sa.1, 2026 (SCI-Expanded, Scopus)
Recent studies on Castanea sativa (C. sativa) leaves have primarily focused on limited phytochemical screening or single-target biological assays, leaving gaps in the comprehensive evaluation of their bioactive potential. This study aimed to systematically investigate the phytochemical composition, antioxidant capacity, multi-enzyme inhibitory activity, and molecular interaction profile of the methanolic extract of C. sativa leaves. UPLC-MS/MS analysis identified ellagic acid, chlorogenic acid, and quinic acid as major constituents, supported by high phenolic (190.556 mg GAE/g) and flavonoid (50.430 mg QE/g) contents. The extract exhibited strong antioxidant properties, particularly in cupric reducing antioxidant capacity (CUPRAC) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) assays, demonstrating activities comparable to those of standard antioxidants. Notably, potent inhibitory effects were observed against carbonic anhydrase (CA) I–II, acetylcholinesterase (AChE) (IC50 = 0.0017 µg/mL), and α-glycosidase (IC50 = 0.0063 µg/mL), with AChE inhibition approaching that of tacrine and α-glycosidase inhibition surpassing acarbose by 2.3-fold. Molecular docking analyses further revealed specific interactions between major phytochemicals and enzyme active sites, supporting the in vitro findings. These results demonstrate that C. sativa leaves represent a promising, sustainable source of bioactive molecules with strong antioxidant and multi-target enzyme inhibition potential, suggesting possible applications in the management of oxidative stress-related conditions, neurodegenerative diseases, and metabolic disorders such as diabetes.