Neuroprotective and Antioxidant Effects of Pseudoelephantopus spicatus

INTRODUCTION: Pseudoelephantopus spicatus has been traditionally employed in ethnomedicine for treating a variety of ailments. However, its neuroprotective and antioxidant properties remain underexplored. This study investigates the phytochemical composition, antioxidant potential, and neuropharmacological effects of its methanolic leaf extract (MEPS). METHOD: Leaves were collected, identified, and subjected to methanolic extraction. Phytochemical profiling was conducted via GC-MS, and antioxidant activity was assessed using DPPH and superoxide scavenging assays. Swiss albino mice were employed in behavioral tests, Hole Board Test (HBT), Elevated Plus Maze (EPM), Forced Swimming Test (FST), and Tail Suspension Test (TST) to evaluate anxiolytic and antidepressant effects. Additionally, in silico molecular docking assessed interactions of major compounds with the GABA receptor. RESULTS: GC-MS revealed key phytochemicals, including 9,12-octadecadienoic acid and hexadecanoic acid methyl ester. MEPS showed moderate antioxidant activity with 13.264 mg GAE/g and 43.692 mg QE/g for phenolics and flavonoids, respectively. Behavioral assays showed dosedependent anxiolytic and antidepressant effects, especially at 200 mg/kg (p < 0.001). Docking studies indicated strong GABA receptor binding, particularly for 9,12-octadecadienoic acid (-6.6 kcal/mol). DISCUSSION: The neuropharmacological effects are attributed to high flavonoid content and specific phytochemicals with known CNS activity. The behavioral improvements and antioxidant activities support MEPS's therapeutic potential in neurological disorders, likely through modulation of oxidative stress and GABAergic pathways. CONCLUSION: MEPS exhibits significant antioxidant, anxiolytic, and antidepressant activities, supported by both in vivo and in silico findings. These results validate its traditional use and warrant further studies for its potential development as a neuroprotective agent.