An Integrated Pharmacological Evaluation and GC-MS/MS-Guided Metabolite Profiling of Diospyros sylvatica Roxb. Leaves Revealing Analgesic, Antioxidant, and Antidiabetic Activities.

Diospyros sylvatica Roxb. (Ebenaceae) is a tropical medicinal plant traditionally used for respiratory, inflammatory, cold, and digestive disorders due to its rich terpenoids, tannins, polyphenols, and naphthoquinones. This study investigated the in vitro antioxidant, in vivo hypoglycemic, and analgesic activities, as well as the in silico molecular interactions, of GC-MS/MS-guided phytochemicals from the leaves. Antihyperglycemic activity was evaluated using the oral glucose tolerance test, and peripheral analgesic activity was assessed using the acetic acid-induced writhing model in Swiss albino mice (n = 6 per group). At the same time, antioxidant potential was determined using the DPPH assay %). The ethyl acetate fraction exhibited the highest antioxidant activity (IC50 = 35.28 µg/mL). At 400 mg/kg, chloroform and ethyl acetate fractions significantly reduced blood glucose by 50.14% and 36.60% at 180 min compared with metformin (64.02%). The n-hexane fraction showed the strongest analgesic activity with 50.40% writhing inhibition compared to diclofenac sodium (69.77%). GC-MS/MS analysis identified 29 compounds, which were further subjected to molecular docking and ADMET analysis, revealing drug-likeness and favorable binding affinities toward targeted receptors. Collectively, these findings demonstrate significant antioxidant, hypoglycemic, and analgesic potentials of D. sylvatica leaves supported by identified bioactive metabolites, warranting further extensive studies for clinical translation.