Anti-Autophagy Mechanism of Zhi Gan Prescription Based on Network Pharmacology in Nonalcoholic Steatohepatitis Rats.
Anti-Autophagy Mechanism of Zhi Gan Prescription Based on Network Pharmacology in Nonalcoholic Steatohepatitis Rats.
复制标题
基于网络药理学的止肝方抗非酒精性脂肪性肝炎大鼠自噬机制研究
DOI：
10.3389/fphar.2021.708479
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发表时间：
2021
影响因子：
5.6
通讯作者：
Ji Y
中科院分区：
文献类型：
--
作者：
Qin C;Luo L;Cui Y;Jiang L;Li B;Lou Y;Weng Z;Lou J;Liu C;Weng C;Wang Z;Ji Y
背景与目的：临床证明炙甘方（ZGP）对非酒精性脂肪性肝炎（NASH）有良好的治疗作用。本研究旨在揭示 ZGP 在 NASH 中作用的潜在分子机制。 方法：采用系统网络药理学来确定 ZGP 在 NASH 中的生物活性成分、潜在靶点和潜在机制。采用高脂（HF）诱导的NASH模型大鼠评估ZGP抗NASH的作用，并验证网络药理学预测的可能的分子机制。 结果：ZGP共获得138个活性成分和366个潜在靶点。此外，还筛选了823个NASH靶点。体内实验表明，ZGP 显着改善了 HF 诱导的 NASH 大鼠的症状。 qRT-PCR和蛋白质印迹分析表明，ZGP可以调节NASH模型大鼠的中枢基因PTEN、IL-6和TNF。此外，ZGP 通过 PINK/Parkin 途径的线粒体融合和裂变抑制线粒体自噬。 结论：ZGP通过线粒体自噬发挥抗NASH作用。这些发现为 ZGP 在 NASH 中的机制提供了新的见解。
Background and Aims: Zhi Gan prescription (ZGP) has been clinically proven to exert a favorable therapeutic effect on nonalcoholic steatohepatitis (NASH). This study purpose to reveal the underlying molecular mechanisms of ZGP action in NASH. Methods: Systematic network pharmacology was used to identify bioactive components, potential targets, and the underlying mechanism of ZGP action in NASH. High fat (HF)-induced NASH model rats were used to assess the effect of ZGP against NASH, and to verify the possible molecular mechanisms as predicted by network pharmacology. Results: A total of 138 active components and 366 potential targets were acquired in ZGP. In addition, 823 targets of NASH were also screened. In vivo experiments showed that ZGP significantly improved the symptoms in HF-induced NASH rats. qRT-PCR and western blot analyses showed that ZGP could regulate the hub genes, PTEN, IL-6 and TNF in NASH model rats. In addition, ZGP suppressed mitochondrial autophagy through mitochondrial fusion and fission via the PINK/Parkin pathway. Conclusion: ZGP exerts its effects on NASH through mitochondrial autophagy. These findings provide novel insights into the mechanisms of ZGP in NASH.
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