Antioxidant and Antihypertensive Activities of Ficus exasperata Vahl Leaves: Integrated In Vitro Evaluation and In Silico Multi-Target Mechanistic Insights.

Hypertension (HTN) remains a major global health challenge and a leading cause of cardiovascular morbidity. The limitations of conventional antihypertensive therapies, including high cost and side effects, highlight the need for alternative interventions. This study evaluated the antioxidant and antihypertensive properties of F. exasperata leaf Vahl extracts using in vitro and in silico approaches. Aqueous (AE) and ethanol (EE) extracts were analyzed for total phenolic and flavonoid contents. Antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, while angiotensin-converting enzyme (ACE) inhibitory activity was compared with captopril. Gas chromatography-mass spectrometry (GC-MS) analysis identified phytochemical constituents. Network pharmacology and molecular docking targeted oxidative stress-induced hypertension-related targets, and molecular dynamics simulations evaluated ligand-protein stability. EE showed higher flavonoid content (274.09 mg QE/g) and stronger antioxidant activity (DPPH IC50 = 6.00 µg/mL) than AE. In contrast, AE demonstrated superior ACE inhibition (IC50 = 5.14 µg/mL), comparable to captopril (IC50 = 5.17 µg/mL). GC-MS identified 77 compounds in EE and 40 in AE, including bioactives with antioxidant effects. Docking analysis revealed strong affinities with nitric oxide synthase 3 (NOS3) and ACE, and simulations confirmed stable ligand-NOS3 interactions. These findings support the therapeutic potential of F. exasperata in HTN management.