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.

Purpose

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

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.

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.

Conclusion

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

中文翻译：

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五味子酚B通过激活小鼠中的PXR和YAP途径促进肝脏肿大

背景

五味子酚B（SolB）是中药五味子或五味子的生物活性成分之一。已证明SolB对药物引起的肝损伤具有保肝作用，并促进肝脏再生。已经发现SolB可以诱导肝肿大，但是所涉及的机制仍然未知。

目的

这项研究旨在探讨参与SolB诱导的肝肿大的机制。

方法

给雄性C57BL / 6小鼠腹膜内注射SolB（100 mg / kg），持续5天。收集血清和肝脏样品进行生化和组织学分析。通过qRT-PCR和Western印迹分析，萤光素酶报告基因分析和免疫荧光研究了SolB的机制。

结果

SolB显着增加了肝细胞大小和增殖，然后促进了肝肿大，而没有肝损伤和炎症。SolB转激活人PXR，在小鼠中激活PXR，并上调其下游蛋白（例如CYP3A11，CYP2B10和UGT1A1）的肝表达。SolB还显着增强了人类细胞系中PXR和YAP的核易位。在小鼠中，YAP信号途径被SolB激活。

结论

这些发现表明，SolB可以显着诱导肝脏肿大，这与PXR和YAP途径的激活有关。