Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice

五味子醇乙通过激活 PXR 和 YAP 通路促进小鼠肝脏肿大

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作者:Ying-Yuan Zhao, Xin-Peng Yao, Ting-Ying Jiao, Jia-Ning Tian, Yue Gao, Shi-Cheng Fan, Pan-Pan Chen, Yi-Ming Jiang, Yan-Ying Zhou, Yi-Xin Chen, Xiao Yang, Min Huang, Hui-Chang Bi

Background

Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown.

Conclusion

These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.

Methods

Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence.

Purpose

This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly.

Results

SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice.

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