Samad_2025_Naunyn.Schmiedebergs.Arch.Pharmacol__

The study aims to evaluate the effect of various doses of gallic acid (GA) on omeprazole (OMZ)-induced depression, memory impairment, oxido-neuroinflammation, and altered serotonergic neurotransmission in the midbrain and cerebral cortex of rats. Forty-eight male rats were divided into six groups (n = 8): Veh (vehicle), Veh + GA (50 mg/kg/ml), Veh + GA (100 mg/kg/ml), OMZ (20 mg/kg/ml), OMZ + GA (50 mg/kg/ml), and OMZ + GA (100 mg/kg/ml). Animals received their respective treatment intraperitoneally, daily for 4 weeks. After that, behavioral analysis for depression and memory function was performed; then, animals were decapitated, and their brains were removed from skulls. Brain regions, i.e., midbrain and cerebral cortex, were isolated for various biochemical and neurochemical studies. Results showed that OMZ-induced depression-like behavior and memory impairment were attenuated by GA in a dose-dependent manner. OMZ instigated decreased antioxidant enzyme activity and serotonergic mechanism, and increased oxido-neuroinflammation and acetylcholinesterase (AChE) activity were normalized by dose-dependent GA administration in both regions. In silico study also showed that GA has a potent antioxidant effect on the brain. In conclusion, the present findings revealed that GA, as a potential agent that reduced PPIs, induced depression-like behavior and memory impairment. The supplementation of GA as a dietary constituent could provide relief against OMZ-induced negative effects.