Integrated LC–MS Profiling, In Vitro Antioxidant Activity, and Exploratory Molecular Docking of Selected Mangifera odorata Fruit Extract Constituents with KEAP1

Abstract

Natural products remain important sources of antioxidant compounds, particularly among underexplored tropical fruits. This study evaluated the antioxidant potential of Kweni (Mangifera odorata) fruit extract by integrating LC–MS profiling, in vitro assays, and molecular docking. Putative compounds were annotated by spectral-library matching. Hydroxyl radical (•OH) and hydrogen peroxide (H₂O₂) scavenging and metal-ion chelating activities were measured, and the corresponding half-maximal inhibitory concentrations (IC₅₀) were determined. Five flavonoid-related candidates (eriodictyol, astilbin, apigetrin, naringenin, and genistein) were selected for docking against Kelch-like ECH-associated protein 1 (KEAP1). The extract showed measurable activity in all three assays, with IC₅₀ values of 67.240 µg/mL for metal-ion chelation, 83.03 µg/mL for H₂O₂ scavenging, and 84.17 µg/mL for •OH scavenging. Among the selected candidates, astilbin and the tentatively annotated apigetrin produced the most favorable Vina scores (−10.2 kcal/mol) and predicted contacts within the modeled KEAP1 pocket. Because the compounds were putatively annotated and the assays used the whole extract, the observed activities cannot be assigned to individual constituents. The docking results indicate possible ligand–KEAP1 interactions but do not demonstrate KEAP1 inhibition, disruption of KEAP1–NRF2 binding, or NRF2 activation. Authentic standards, isolated compounds, biochemical binding assays, and cellular studies are required for confirmation.