Antidepressant‑like activity of Chaihu‑Shugan‑San aqueous extract in rats and its possible mechanism

Background: Chaihu‑Shugan‑San (CHSGS), a traditional Chinese medicinal formula, is commonly used for the treatment of depression in China. However, the molecular mechanism underlying its antidepressant action is unknown. Objective: The objective of this study is to evaluate the antidepressant‑like effects of CHSGS and further explore the possible molecular mechanism implicated in its actions. Materials and Methods: The rats were randomly divided into four groups: The normal control group, the model control group, the CHSGS group and the fluoxetine control group. The antidepressant‑like effects of CHSGS aqueous extract were assessed in rats exposed to chronic mild stress (CMS) using the open‑field test and sucrose water consumption test, its underlying mechanism of anti‑depression was explored by determining the effect of CHSGS on the extracellular signal‑regulated kinase (ERK) and phospho‑ERK (P‑ERK) in the hippocampus using western blot. The aqueous extract of CHSGS at a dose of standard (5.9 g/kg·d) was administered intragastrically for 14 days during the CMS model while the fluoxetine control group was given at the same time using fluoxetine hydrochloride (1.8 mg/kg·d). Results: The stressed rats demonstrated decreased locomotor activity in open field test and reduction in sucrose consumption and decreased levels of P‑ERK1/2 and the ratio of P‑ERK1/2 to total ERK1/2 in the hippocampus. CHSGS alleviated the depressive‑like behaviors and increased levels of P‑ERK1/2 and the ratio of P‑ERK1/2 to total ERK1/2 in stressed rats as well as fluoxetine. Conclusion: In summary, these results suggest that CHSGS aqueous extract possesses an antidepressant‑like activity in CMS induced depression model rats, which might be mediated, at least in part, by reversing the stress‑induced disruption of ERK activity.