Schisandrin B regulates macrophage polarization and alleviates liver fibrosis via activation of PPARγ.

Background: Schisandrin B (Sch B), the main ingredient of , displays many bioactivities. This study aimed to identify the drug target of Sch B against liver fibrosis and describe the related molecular mechanisms.

Methods: The effects of Sch B on liver fibrosis and macrophage polarization was investigated and . Furthermore, we analyzed the regulatory effect of Sch B on peroxisome proliferator-activated receptor gamma (PPARγ).

Results: Our data showed that Sch B dramatically alleviated liver inflammation and fibrosis and inhibited macrophage activation via PPARγ. Sch B binds with PPARγ by molecular docking. Immunofluorescence double staining showed that PPARγ was mainly expressed in macrophages rather than hepatic stellate cells (HSCs) in liver fibrosis. Importantly, Sch B strongly inhibited macrophage polarization in fibrotic livers compared with the model group. Further, the results revealed that Sch B efficiently inhibited macrophage polarization and also decreased the levels of inflammatory cytokines in vitro. Knockdown of PPARγ by small interfering RNA (siRNA) inhibited the effect of Sch B on macrophage polarization. Mechanistically, Sch B regulated macrophage polarization through inhibition of the nuclear factor (NF)-κB signaling pathway via PPARγ both and .

Conclusions: These results suggested that Sch B alleviated carbon tetrachloride (CCl)-induced liver inflammation and fibrosis by inhibiting macrophage polarization via targeting PPARγ.