Abstract
BACKGROUND: Depression affects millions globally, with existing treatments having many side effects. Withania somnifera (WS) shows potential as an antidepressant and neuroprotective agent, possibly by influencing brain-derived neurotrophic factor (BDNF)-related pathways. AIM: This study evaluated the effect of WS alone and in combination with fluoxetine on neuritin, NARP, and BDNF Exon-III gene expression in the hippocampus of male Wistar rats subjected to chronic unpredictable mild stress (CUMS). MATERIALS AND METHODS: Thirty male Wistar rats were divided into five groups (n = 6 each): normal group (NG), disease control (DC), standard treatment (ST), WS, and combination group of fluoxetine and WS (FW). Depression was induced using CUMS, except in the NG. The sucrose preference test confirmed depression at the end of 3(rd) week and assessed treatment effects at the end of 7(th) week. Gene expression in the hippocampus was analyzed through real-time PCR at the end of 7(th) week. RESULTS: After 7 weeks, the ST, WS, and FW groups showed a significant increase in sucrose preference compared to the DC group. The ST and FW groups showed significant upregulation of all three genes selected in the present study. Comparison between NG and FW groups showed no significant difference in gene expression. CONCLUSION: This study highlights the antidepressant effects of WS by demonstrating its effect on BDNF-associated gene expression. Fluoxetine combined with WS demonstrated additive effects which proves an adjuvant role of WS in the treatment of depression. Further studies involving human subjects are essential to validate the antidepressant effects of WS and its additive effects with fluoxetine.