Saikosaponin A Inhibits LPS-Induced Endometritis in Mice Through Activating Nrf2 Signaling Pathway

Saikosaponin A (SSA) is the major triterpenoid glycoside isolated from Bupleurum falcatum. In this study, we reported the protective effects and mechanism of SSA on lipopolysaccharide (LPS)-induced endometritis in mice. The pathological changes and myeloperoxidase (MPO) activity of uterus tissues were evaluated by hematoxylin and eosin (H&E) staining and MPO detection kit. Inflammatory cytokines TNF-α, IL-1ß, and IL-6 production were detected by ELISA. The expression of protein was measured by western blot analysis. The results showed that SSA administration inhibited inflammatory cell infiltration as confirmed by the decreased MPO activity. LPS-induced uterus histological changes were also suppressed by SSA. Meanwhile, LPS-induced TNF-α, IL-1ß, and IL-6 production were reduced by SSA administration. The phosphorylation levels of nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) induced by LPS were inhibited by SSA. In addition, the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) were upregulated by SSA in a concentration-dependent manner. These results provide evidence that SSA protects against LPS-induced endometritis through inhibiting inflammatory response. SSA may be used as a potential therapeutic agent for the treatment of endometritis.