五味子醇 B 通过激活小鼠 PXR 和 YAP 通路促进肝脏增大。
Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice.
机构信息
Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
出版信息
Phytomedicine. 2021 Apr;84:153520. doi: 10.1016/j.phymed.2021.153520. Epub 2021 Feb 17.
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.
背景
五味子醇 B（SolB）是来源于传统中药五味子或华中五味子的一种生物活性成分。已有研究表明，SolB 对药物性肝损伤具有肝保护作用，并能促进肝再生。研究发现 SolB 可诱导肝肿大，但具体机制尚不清楚。
目的
本研究旨在探讨 SolB 诱导肝肿大的相关机制。
方法
雄性 C57BL/6 小鼠腹腔注射 SolB（100mg/kg），连续 5 天。收集血清和肝组织样本进行生化和组织学分析。采用 qRT-PCR 和 Western blot 分析、荧光素酶报告基因检测和免疫荧光实验来研究 SolB 的作用机制。
结果
SolB 可显著增加肝细胞体积和增殖，进而促进肝脏增大而无肝损伤和炎症。SolB 可直接激活人 PXR，并在小鼠中激活 PXR，上调其下游蛋白，如 CYP3A11、CYP2B10 和 UGT1A1 的表达。SolB 还可显著增强人细胞系中 PXR 和 YAP 的核转位。SolB 可在小鼠中激活 YAP 信号通路。
结论
这些发现表明，SolB 可显著诱导肝脏增大，其与 PXR 和 YAP 通路的激活有关。
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