Saikosaponin a alleviates depressive-like behavior by regulating the BDNF-TrkB-CREB signaling pathway in a mouse model of chronic unpredictable mild stress

This study aimed to determine the effect of Saikosaponin a (SSa) in a model of depression induced by chronic unpredictable mild stress (CUMS) and to investigate whether SSa plays an antidepressant role by regulating the BDNF-TrkB-CREB signaling pathway. A mouse model of depression was established and treated with different concentrations of SSa (15, 30 and 60 mg/kg). Behavioral tests, including sucrose preference test (SPT), open-field test (OFT), forced swim test (FST) and tail suspension test (TST). mRNA levels of BDNF, TrkB and CREB in the hippocampus of mice were detected by QRT-PCR. Protein levels of BDNF, pTrkB, TrkB, pCREB and CREB were measured by Western blot. Results showed that compared to the model group, the SSa treatment significantly increased the sucrose preference, improved the spontaneous activity in the OFT, and reduced the immobility time in the TST and FST. In addition, SSa effectively inhibited CUMS induced mRNA reductions in BDNF, TrkB and CREB and up-regulated CUMS induced protein expression levels of BDNF, pTrkB, TrkB, pCREB and CREB in the mouse hippocampus. In conclusion, our results indicate that SSa can effectively improve CUMS-induced depressive-like behavior in mice, which may be achieved by activating the BDNF-TrkB-CREB signaling pathway.