Pharmacological Investigation of Methanolic Extract of Gmelina arborea for Anxiolytic Activity and Neurotransmitter Modulation

Introduction: Anxiety disorders are prevalent neuropsychiatric conditions associated with oxidative stress and neurotransmitter imbalance, particularly gamma-aminobutyric acid (GABA) and serotonin. Herbal medicines with antioxidant and neuroprotective properties may offer safer therapeutic alternatives. The present study investigated the anxiolytic potential of the methanolic extract of Gmelina arborea (MEGA) in stress-induced murine models. Materials and Methodology: Acute oral toxicity was evaluated as per OECD guidelines. Swiss albino mice (25–35 g) were subjected to electric foot shock and restraint stress-induced anxiety models. Behavioral assessments were conducted using the Elevated Plus Maze (EPM) and Light–Dark Transition (LDT) tests. MEGA was administered orally at doses of 200 and 400 mg/kg, while Diazepam (1 mg/kg) served as the standard. In vitro antioxidant activity was assessed using DPPH, hydrogen peroxide, and nitric oxide scavenging assays. Neuroprotective activity was evaluated in SH-SY5Y neuroblastoma cells exposed to H₂O₂-induced oxidative stress. Brain GABA and serotonin levels were estimated posttreatment. Results: MEGA was safe up to 2000 mg/kg with no mortality observed. The extract exhibited dose-dependent antioxidant activity and significant protection against oxidative stress in SH-SY5Y cells. In vivo studies demonstrated a significant increase (p < 0.05) in time spent in open arms (EPM) and light compartment (LDT) compared to disease control. Biochemical analysis revealed restoration of GABA and serotonin levels comparable to Diazepam-treated groups. Conclusion: The findings confirm that Gmelina arborea possesses significant anxiolytic, antioxidant, and neuroprotective properties, supporting its potential as a natural therapeutic candidate for anxiety disorders.