Antidepressant Role of Stachydrine in LPS Induced Depression by Targeting Neuroinflammatory Signaling

Abstract

Depression is a multifactorial neuropsychiatric disorder frequently associated with neuroinflammatory processes. Docking analyses revealed a favorable binding affinity of stachydrine, a natural pyrrolidine alkaloid, to the NLRP3 receptor, suggesting its potential modulatory effects on inflammasome activity. To investigate its antidepressant-like effects, adult male Sprague–Dawley rats were randomly assigned to four groups. Saline control, LPS-induced depression, stachydrine treated (50 mg/kg), and fluoxetine treated (20 mg/kg). Behavioral assessments were performed using the forced swim test, while molecular analyses focused on NF‑κB and NLRP3 expression via real time polymerase chain reaction, key mediators of neuroinflammation. LPS administration significantly increased immobility time and reduced struggling time, indicating depressive-like behavior. Stachydrine treatment effectively reversed these behavioral deficits, demonstrating antidepressant like effects comparable to fluoxetine. At the molecular level, stachydrine markedly attenuated LPS-induced upregulation of NF‑κB and NLRP3, indicating suppression of inflammasome-mediated neuroinflammatory pathways. These results suggest that stachydrine exerts neuroprotective and antidepressant like effects through modulation of inflammatory signaling. Overall, stachydrine emerges as a promising natural compound for further development as a neuroimmune targeted therapeutic agent in depression. Future investigations incorporating protein level validation, cytokine profiling and additional behavioral analysis are required to fully elucidate its pharmacological potential.