Antidepressant effects of piperine and its neuroprotective mechanism in rats

Objective: To study the antidepressant effects of piperine in chronic unpredictable mild stress (CUMS) rats and to explore the underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis. Methods: Fifty rats were housed alone and exposed to an unpredicted sequence of mild stressors to induce GUMS, and then were divided into untreated group, desipramine group and low-, medium- and high-dose piperine groups. Another 10 normal rats were used as normal control. The behavior of the rats was detected by body weight and sucrose preference test, and the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in different groups were observed by radioimmunoassay. Results: The results indicated that after 21-day administration, piperine at concentrations of 10 and 20 mg/kg could significantly improve the behavioral disorder by increasing sucrose consumption. Piperione at concentrations of 5, 10 and 20 mg/kg could remarkably reduce serum ACTH and CRH levels in the CUMS rats, but had little effect on the content of CORT. Conclusion: Piperine can relieve depression in CUMS rats by modulating the function of HPA axis.