摘要OBJECTIVE The aim of the present study was to evaluate the protective effects of momordica charantia polysaccharides(MCP)on depressive animal model induced by chronic social defeat stress(CSDS)and explore the underlying mechanisms.METHODS We established CSDS depressant mouse model and treated CSDS mice with MCP.Sucrose preference,forced swim test(FST)and social interaction test(SIT)were used to measure behaviors changes.We used ELISA,Q-PCR and western blot to test the levels of cytokines in the hippocampus. RESULTS The results showed that chronic administration of MCP(100,200 and 400 mg·kg-1)significantly prevented depressive-like behaviors in mice as assessed by social interaction (SIT), tail suspension (TST) and sucrose preference tests (SPT).It was showed that the elevation of proinflammatory cytokines(TNF-α,IL-6,and IL-β)concentra-tions,up-regulation of JNK3,c-Jun,and P-110β protein expressions in the hippocampus of CSDS model. Moreover,reduction activity of PI3K and phosphorylation level of protein kinase B(AKT)was also observed in the hippocampus of CSDS model.All above phenomenon were reversed after MCP intervened.Further-more,the protective effects of MCP on the CSDS mice were partly inhibited by the specific phosphati-dylinositol 3-kinase (PI3K)inhibitor, LY294002. CONCLUSION The protective effects of MCP against depressive-like effects in CSDS mice might reduce neuroinflammatory and involve in attenuation of JNK3/PI3K/AKT pathway in the hippocampus.