Antinociceptive and Central Nervous System Depressant Effects of Grewia serrulata Leaf Extracts Through In Vivo and In Silico Investigations

This study delves into the pain‐relieving and depressant attributes of G. serrulata leaf extract, employing both in vivo and in silico methods. Leaf extracts (aqueous, chloroform, methanol, dichloromethane, and petroleum ether) were evaluated for analgesic effects via hot plate and acetic acid‐induced writhing tests and central nervous system (CNS) depressant effects through head dip, open field, and hole‐cross tests in mice. The dichloromethane extract displayed the most pronounced analgesic activity, reducing abdominal writhing by 72.16% and increasing paw licking time by 74.46% at 100 mg/kg. The petroleum ether extract showcased the strongest CNS depressant effects, inhibiting 77.57% in the head dip, 89.91% in the open field, and 83.02% in the hole‐cross tests at the same dose. In molecular docking, ligand L‐8 demonstrated the highest binding affinity (−7.4 and −7.2 kcal/mol with the cyclooxygenase‐II (COX‐II) and gamma‐aminobutyric acid (GABA) receptors, respectively). Molecular docking revealed strong interactions between the proteins and ligands, which were further validated by the 100 ns molecular dynamics simulation. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis indicated promising pharmacokinetic properties, highlighting the therapeutic potential of G. serrulata compounds for pain relief and anxiety management. These findings support further exploration for drug development.