Comprehensive UPLC-MS/MS-based metabolic profiling, antioxidant potential, enzyme inhibition, and molecular docking studies of Ficus carica L. leaves: Potential for functional food applications

Fig (Ficus carica L.) is a fruit tree consumed worldwide as a functional food. While its fruit is well-studied, the phytochemicals and biological activities of its leaves have not been reported in detail. This study comprehensively investigated phytochemical composition and biological activities of methanol extract from Ficus carica L. leaves from Nazilli, Türkiye. Phytochemical analysis was performed using UPLC-MS/MS. Antioxidant capacity was evaluated using electron transfer-based analyses (Fe3+ reduction, CUPRAC, FRAP) and radical scavenging methods (DPPH, ABTS, DMPD). Enzyme inhibition effects were examined on carbonic anhydrases (CA I-II), acetylcholinesterase (AChE), and α-glycosidase (α-Gly). High total phenolics (86.111 μg GAE/mg) and flavonoids (104.086 μg QE/mg) were detected. UPLC-MS/MS identified 17 bioactive compounds, with chlorogenic acid (17069.52 ng/mL) as dominant. The extract showed notable antioxidant activity, performing best in CUPRAC (exceeding Trolox) and ABTS assays. It significantly inhibited all tested enzymes with IC₅₀ values of 0.024 μg/mL for CA I, 0.025 μg/mL for CA II (approximately 4-fold higher than acetazolamide), 0.002 μg/mL for AChE (half as potent as tacrine: 0.001 μg/mL), and 0.009 μg/mL for α-Gly (1.7-fold more potent than acarbose: 0.015 μg/mL). Molecular docking confirmed favorable binding energies (all below −7.00 kcal/mol) between chlorogenic acid and target enzymes. This study represents the first comprehensive metabolic profiling of fig leaves from Nazilli region and reveals their potential as natural ingredients for nutraceutical products owing to their rich phenolic content, notable antioxidant capacity, and potent enzyme inhibitory properties relevant to dietary management of various health conditions.