Chaihu Shugan San, a traditional Chinese medicine formula, may combat depressive symptoms in female mice through controlling hippocampal inflammation and enhancing neuroplasticity.
The experiment was conducted on adult female mice who underwent a 5-week period of chronic unpredictable mild stress to simulate depressive behaviors. During the last two weeks of this period, varying doses of Chaihu Shugan San were administered to the mice and fluoxetine was used as the positive control. Various tests, such as forced swimming, sucrose preference, open field, and tail suspension tests were utilized to assess the behavior of the mice, while hippocampal interleukin-6, cAMP, CaMKII, and BDNF levels were measured. Additionally, acute hippocampal microinjection of recombinant interleukin-6 and systemic administration of the CaMKII inhibitor were used for further mechanistic validation.
Chaihu Shugan San's treatment showed significant reduction of depressive-like behaviors followed by IL-6 reduction and increase in the hippocampal cAMP, CaMKII activity, and BDNF expression. Unexpected elevation of IL-6, however, nullified both the behavioral improvements and molecular actions of Chaihu Shugan San. Additionally, the inhibition of CaMKII ceased the behavioral improvements induced by Chaihu Shugan San and its upregulation of cAMP-BDNF signalling, without affecting the baseline behaviors. The study also established that Chaihu Shugan San did not induce any anxiogenic or locomotor side effects.
