Abstract:Objective: To observe the antidepressant effect of piperine and its neuroprotective mechinism. Method: The behavioral studies were performed in forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, CORT-induced neuroblastoma SH-SY5Y cells and isolated and cultured neural progenitor cells. By using MTT assay, the effect of piperine on neural cells proliferation was observed. Result: The research results indicated that after a week of administration, piperine (10, 20 mg·kg-1) could significantly reduce the duration of immobility in both FST and TST. Piperine has the protective effect on neuroblastoma cells and increased proliferation of hippocampus neural progenitor cells. Conclusion: In the present study, we demonstrated that the antidepressant-like effects of piperine and its mechanisms might be involved by up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity.