Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Nypa fruticans (Arecaceae) has long been used in traditional medicine for the management of anxiety, insomnia, and depressive symptoms. However, scientific validation of its neuropharmacological activities and active constituents is limited. AIM OF THE STUDY: This study evaluated the anxiolytic, antidepressant, and sedative activities of the ethyl acetate fraction of Nypa fruticans (NF) leaves (EaNFL) through in vivo behavioral models and in silico molecular docking (MD) and molecular dynamics simulations (MDS) to provide scientific support for its traditional CNS use. MATERIALS AND METHODS: Neuropharmacological activities of EaNFL were assessed in mice using elevated plus maze (EPM), hole board test (HBT), open field test (OFT), hole cross test (HCT), tail suspension test (TST), and forced swimming test (FST). Major phytochemicals identified from EaNFL were subjected to MD analysis against voltage-gated potassium channels (PDB: 4UUJ), GABA-A receptors (PDB: 6X3X), and human serotonin transporter (PDB: 5I6X). Top-binding compounds were further analyzed using MDS to assess receptor-ligand stability. RESULTS: EaNFL (400 mg/kg) showed significant anxiolytic activity in EPM and HBT, dose-dependent sedative properties in HCT and OFT, and notable antidepressant-like effects in TST and FST. However, reduced locomotor activity may have contributed to some of the observed behavioral outcomes. MD revealed that myricetin (CID 5281672) and quercetin (CID 5280343) predicted stable interactions and favorable binding affinities with major CNS-related receptors, as suggested by MDS analysis. Additionally, (-)-epicatechin (CID 72276) and rosmarinic acid (CID 5281792) exhibited favorable receptor interactions, suggesting therapeutic potential in anxiety, insomnia, and depression. CONCLUSIONS: EaNFL possesses notable anxiolytic, sedative, and antidepressant-like effects, supporting its traditional use in CNS disorders. MD and MDS findings suggest that myricetin, quercetin, and (-)-epicatechin acid may be key bioactive constituents underlying these effects. Further studies are warranted to elucidate molecular mechanisms and explore its pharmaceutical potential.