Neuroactive Phytoconstituents of Ficus mysorensis: A New Perspective on Anticonvulsant and Antipsychotic Therapies

Introduction: Ficus mysorensis is traditionally used in ethnomedicine, yet its neuropharmacological potential remains underexplored. The plant's diverse phytochemicals may confer anticonvulsant, sedative, and anxiolytic effects. This study aimed to evaluate its neuropharmacological activities, characterize its phytochemical composition, and elucidate molecular interactions with Central Nervous System (CNS) targets through docking studies. Methods: Successive extraction was performed using petroleum ether, ethyl acetate, and 70% ethanol. Extracts underwent preliminary phytochemical screening, HPTLC (High-Performance Thin Layer Chromatography) analysis, and GC-MS (Gas Chromatography-Mass Spectrometry) analysis. Neuropharmacological evaluations included in vivo models: Maximal Electroshock (MES) and Pentylenetetrazol (PTZ) induced seizures (anticonvulsant), pentobarbital-induced sleep (sedative), and elevated plus maze/open-field tests (anxiolytic). Molecular docking was conducted using Schrödinger Maestro against dopamine D2 receptors, with Risperidone as the reference ligand. MMGBSA binding energy and hydrogen bond interactions were used to determine binding efficiency. Results: Phytochemical analysis confirmed the presence of flavonoids, alkaloids, terpenoids, and glycosides. GC-MS identified major constituents, including akuammilan-17-ol and 1,6;3,4- dianhydro-2-deoxy-β-D-lyxo-hexopyranose. The Hydroalcoholic Extract (HFM) showed 16.67% seizure protection in PTZ-induced seizures. In silico results revealed that Risperidone exhibited a docking score of -11.390 kcal/mol and an MMGBSA energy of -91.17 kcal/mol, with key hydrogen bonds to Asp114, Trp386, and Phe390, validating a strong binding affinity. Discussion: HFM demonstrated moderate neuropharmacological efficacy, supported by bioactive constituents that showed strong in silico binding to central nervous system targets, particularly dopamine D2 receptors. Conclusion: This study highlights Ficus mysorensis as a promising source of neuroactive compounds with anticonvulsant, sedative, and anxiolytic potential, warranting further investigation and the isolation of lead constituents for the development of CNS drugs.