In vivo and in silico evaluation of anxiolytic, antidepressant and cognitive enhancing activities of Maesa chisia leaves

Neurodegenerative and neuropsychiatric disorders remain a major health challenge, and natural products offer potential therapeutic leads. This study aimed to evaluate the neuropharmacological potential of Maesa chisia methanolic extract (MEMC) using in vivo behavioral assays and in silico molecular dynamics (MD) simulation. Phytochemical profiling of MEMC was performed using GC-MS. Anxiolytic, antidepressant, cognitive, and motor-enhancing effects were assessed in mice using open field (OFT), hole cross (HCT), elevated plus maze (EPM), hole board (HBT), forced swim (FST), tail suspension (TST), Morris water maze (MWMT), and single pellet reaching task (SPRT). MD simulation was conducted to evaluate the binding stability of the identified bioactive compounds with acetylcholinesterase (AChE). GC-MS identified key constituents, including phytyl tetradecanoate, 5α-cholestan-3-one, and 3β,5α-cholestane-3,5-diol. MEMC demonstrated significant, dose-dependent anxiolytic activity (OFT, HCT, EPM, HBT; 500 mg/kg, P < 0.05) and antidepressant effects (FST, TST; P < 0.05). Cognitive enhancement was indicated by increased target-quadrant time in MWMT (250 and 500 mg/kg; P < 0.05), and motor skill improvement was confirmed via SPRT. MD simulation revealed stable interactions of phytyl tetradecanoate with AChE (ΔGbinding = − 60.59 kcal/mol), with 5α-cholestan-3-one and 3β,5α-cholestane-3,5-diol showing favorable structural stability (RMSD, RMSF, Rg, SASA, H-bonds). MEMC exhibits significant anxiolytic, antidepressant, cognitive-enhancing, and motor-learning activities. The combination of in vivo and in silico findings highlights MEMC as a promising candidate for further development in neuropharmacological therapies.