LC–MS/MS-Based Phytochemical Profiling, In Vitro Antioxidant and Anti-Inflammatory Activities, and Molecular Docking Studies of Hydroethanolic Extract from Foeniculum vulgare Leaves of Western Algeria

Abstract

Compounds derived from natural sources remain a cornerstone for the development of prophylactic and therapeutic strategies in human healthcare. In this study, we aimed to systematically explore the phytochemical composition and antioxidant and anti-inflammatory activities of Foeniculum vulgare(F.vulgare) leaf hydroalcoholic extract (HEE) using in vitro and in silico approaches. The extract, obtained by maceration at room temperature, exhibited considerable levels of total polyphenols (23.80 ± 0.19 mg GAE/g) and flavonoids (17.62 ± 0.99 mg QE/g). LC-MS/MS profiling revealed a diverse array of bioactive molecules, including chlorogenic acid, ferulic acid, salicylic acid, rutin, trans-cinnamic acid, gentisic acid, vanillin, quercetin, morin, and caffeic acid, with chlorogenic acid and trans-ferulic acid as the major constituents. HEE displayed pronounced, dose-dependent antioxidant activity, with IC₅₀ values of 15.39 ± 0.96 µg/mL (DPPH) and 19.36 ± 0.16 µg/mL (H₂O₂). A marked anti-inflammatory effect was also observed, reaching 71.53% inhibition of bovine serum albumin (BSA) denaturation at 500 µg/mL, with an IC₅₀ of 111.53 ± 0.26 µg/mL. Molecular docking studies demonstrated that phenolic compounds, particularly rutin and quercetin, possess strong binding affinities toward multiple inflammatory targets, suggesting a synergistic, multi-target mechanism rather than the action of a single dominant compound. To the best of our knowledge, this is the first study to investigate the bioactive potential of Foeniculum vulgare leaves in Algeria and North Africa, underscoring their value as a natural source of bioactive compounds with promising applications in managing oxidative stress and inflammation, and in the development of plant-based products for pharmaceutical, agricultural, and food sectors.