乌兰十三味汤散中降压成分调节肝纤维化/肝星状细胞活化通路的网络药理学研究

Research on network pharmacology of Wu-Lan Thirteen-flavor Decoction Powder’s active ingredients in regulating hepatic fibrosis/hepatic stellate cell activation pathway

目的:通过网络药理学、分子对接技术及薄层色谱法探讨乌兰十三味汤散中降压成分调节肝纤维化/肝星状细胞活化通路的作用机制。方法:通过联合运用TCMSP等多个数据库,检索乌兰十三味汤散活性化合物和其作用靶点,与高血压病靶点相匹配,筛选出乌兰十三味汤散治疗高血压病的潜在作用靶点。利用Ingenuity Pathway Analysis软件对潜在靶点进行核心分析、网络构建,对其中交联度较高的化合物进行分子对接及薄层色谱验证。结果:从乌兰十三味汤散中筛选得到活性化合物214种,作用于高血压病的潜在靶点212个,通过构建活性成分-肝纤维化/肝星状细胞活化信号通路-作用靶点互作网络图和进行分子对接验证,发现槲皮素、木犀草素、氧化苦参碱能通过作用于CAM、CASP3、FOS、NFKBIA、STAT3、TGFB1等主要靶点,调控肝纤维化/肝星状细胞活化信号通路,从而降低门静脉高压。进一步采用薄层色谱法,鉴定出乌兰十三味汤散中含有氧化苦参碱。结论:乌兰十三味汤散中降压成分抑制肝星状细胞活化从而发挥抗肝纤维化作用,最终降低门静脉高压。

Objective:To explore the mechanism of antihypertensive components in Wu-Lan Thirteen-flavor Decoction(WLTd)regulating hepatic fibrosis/hepatic stellate cell activation pathway by network pharmacology,molecular docking and thin layer chromatography.Methods:Active compounds of WLTd from TCMSP and other databases were collected and screened for the potential targets in the treatment of hypertension.Ingenuity Pathway Analysis software was used for core analysis and network construction of potential targets.Compounds with high cross-linking degree were verified by molecular docking and thin layer chromatography(TLC).Results:When 214 WLTd active compounds were screened,a total of 212 potential hypertension targets were identified.Collectively,hepatic fibrosis/hepatic stellate cell activation signal pathway ranked second among hypertension regulating pathways.The interaction network diagram of active component-pathway-action target prediction and molecular docking verification suggested that quercetin,luteolin and oxymatrine may regulate hepatic fibrosis/hepatic stellate cell activation signaling pathway by acting on CAM,CASP3,FOS,NFKBIA,STAT3 and TGFB1,thus reducing portal hypertension.Further TLC confirmed the presence of oxymatrine in WLTd.Conclusion:The antihypertensive components in WLTd may inhibit the activation of hepatic stellate cells and thus play an anti-fibrosis role,ultimately reducing portal hypertension.