The total alkaloids of Sophora alopecuroides L. improve depression-like behavior in mice via BDNF-mediated AKT/mTOR signaling pathway

Depression has become a global public health problem and the development of new highly effective, low-toxicity antidepressants is imminent. Sophora alopecuroides L. is a common medicinal plant, which has therapeutic effect on central nervous system diseases.In this study, the antidepressant effect of total alkaloids (ALK) isolated from Sophora alopecuroides L. was explored and the mechanism was further elucidated.A primary neuronal injury model was established in vitro by corticosterone. ICR mice were then selected to construct an in vivo model of chronic unpredictable mild stress (CUMS)-induced depression, and the ameliorative effects of ALK on depression were examined by various behavioral tests. The antidepressant molecular mechanism of ALK was subsequently revealed by ELISA, Western blot, immunohistochemistry and Golgi staining.BDNF secretion as well as TrkB and ERK phosphorylated protein levels were found to be improved in primary cortical neurons, along with improved dendritic complexity of neurons. The results of in vivo showed that the depression-like behavior of CUMS-induced mice was reversed after 2 weeks of continuous gavage administration of ALK, and the neurotransmitter levels in the plasma of mice were increased. Moreover, the expression levels of key proteins of BDNF-AKT-mTOR pathway and the complexity of neuronal dendrites were improved in the prefrontal cortex of mice.These findings indicate that ALK of Sophora alopecuroides L. can effectively improve the depressive phenotype of mice, possibly by promoting the expression of BDNF in prefrontal cortex, activating the downstream AKT/mTOR signal pathway, and ultimately enhancing neuronal dendritic complexity.