[Chaihu Shugan San inhibits C3/C3aR-mediated microglial M1 polarization to improve hippocampal synaptic plasticity in mice with menopausal syndrome with liver qi stagnation].

Abstract

Objectives: To investigate the therapeutic mechanism of Chaihu Shugan San (CSS) for treatment of menopausal syndrome (MPS) with liver qi stagnation.

Methods: Fifty-six female C57BL/6 mice were randomized into sham-operated group (n=13) and bilateral ovariectomy (OVX) groups (n=43), and the latter group was further randomized equally into menopausal group, menopausal liver qi stagnation (MPS+CUMS) group subjected to chronic unpredictable mild stress (CUMS), and CSS treatment group (with CSS gavage at daily dose of 6.47 g/kg for 28 days). MPS model establishment was validated by vaginal smears and behavior tests. The levels of sex hormones, neurotransmitters, and inflammatory cytokines in the serum and hippocampus were measured by ELISA. Hippocampal morphology was observed using HE and Golgi staining, and immunofluorescence staining and Western blotting were used to detect the expressions of microglial markers, synaptic plasticity proteins and C3/C3aR pathway proteins in the hippocampal CA1 region.

Results: The OVX mice showed disrupted estrous cycles. The MPS+CUMS mice exhibited obvious depression-like behaviors, abnormal sex hormones and neurotransmitters, elevated inflammatory factors, hippocampal CA1 neuronal loss with disordered arrangement and pyknosis, reduced dendritic spines, increased microglial markers, decreased synaptic plasticity proteins, and upregulated C3/C3aR pathway. All these changes were significantly improved or corrected after CSS treatment in MPS+CUMS mice.

Conclusions: CSS alleviates MPS with liver qi stagnation possibly by inhibiting C3/C3aR-mediated M1 microglial polarization and improving synaptic plasticity.