Emblica officinalis Fraction Mitigates Depression via PI3K‐AKT Pathway: A Pharmacological Study

This study investigates the antidepressant potential of a pyrogallol-enriched fraction of Emblica officinalis Gaertn. fruit (PEFEO) in a chronic unpredictable mild stress (CUMS) model of depression in mice, supported by in silico and in vivo evaluations. In vivo studies were conducted with PEFEO (100 and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) as a standard. Behavioural assessments, including forced swim, Y-maze, open field, and sucrose preference tests, demonstrated the antidepressant effects of PEFEO. Serum pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) were quantified using ELISA, revealing significant reductions following PEFEO treatment. In silico ADMET profiling indicated favourable pharmacokinetic properties of pyrogallol. Network pharmacology suggested involvement of the PI3K signalling pathway in mediating its antidepressant effect, further supported by molecular docking and dynamic simulations with key target genes (NFKB1, CHRM1, CCNE1). Collectively, the findings suggest that PEFEO mitigates depression by modulating behavioural responses and suppressing inflammatory mediators, potentially via PI3K-AKT pathway regulation. This integrative approach underscores pyrogallol as a promising phytoconstituent for the management of depression with associated anti-inflammatory effects.