基于网络药理学的四逆散保肝作用机制研究

Mechanism of Sini Powder on protecting liver based on network pharmacology

目的基于网络药理学探讨四逆散治疗慢性肝炎、脂肪肝与肝癌的物质基础和保肝的作用机制,同时揭示四逆散治疗肝病"异病同治"的分子机制。方法利用TCMSP、CTD、Genecards、Omim等数据库与相关文献检索四逆散有效化学成分、靶点和慢性肝炎、脂肪肝、肝癌疾病靶点;利用TBtools软件获取四逆散保肝作用的潜在靶点;利用Cytoscape3.7.2软件构建"有效化学成分-靶点"网络与潜在靶点蛋白互作网络;利用Uniprot数据库对潜在靶点进行注释;利用David数据库对潜在靶点进行基因本体(GO)生物功能与基因组百科全书(KEGG)通路富集分析。结果共获取四逆散有效化学成分137个、靶点223个,慢性肝炎靶点478个,脂肪肝靶点17 277个,肝癌靶点16 930个,四逆散保肝作用的潜在靶点30个。GO生物功能与KEGG通路富集分析显示潜在靶点共涉及178个生物过程,参与51条信号通路,排名前20的通路中与肝病相关的有9条。结论四逆散可能是通过调控IL-6、VEGFA、EGFR、PPARG、CASP3等潜在靶点和HIF-1、TNF、PI3K-Akt等相关信号通路,发挥抗炎、抗氧化应激、抑制细胞凋亡等功能,从而对肝脏起到保护作用。

Objective To explore the material basis and hepatoprotective mechanism of Sini Powder in the treatment of chronic hepatitis, fatty liver and liver cancer based on network pharmacology, and reveal the molecular mechanism of Sini Powder in the treatment of liver diseases "treating different diseases with same treatment". Methods The effective chemical constituents and targets of Sini Powder and the disease targets of chronic hepatitis, fatty liver and liver cancer were searched by TCMSP, CTD, Genecards, Omim and related literatures. The potential targets of hepatoprotective effect of Sini Powder were obtained by TBtools software, the interaction network of "effective chemical composition-target" and potential target proteins was constructed by Cytoscape 3.7.2 software, and the potential targets were annotated by Uniprot database. David database was used to analyze GO biological function and KEGG pathway enrichment of potential targets. Results A total of 137 effective chemical constituents, 223 targets, 478 targets for chronic hepatitis, 17277 targets for fatty liver, 16930 targets for liver cancer, and 30 potential targets for hepatoprotection were obtained. GO biological function and KEGG pathway enrichment analysis showed that a total of 178 biological processes and 51 pathways were involved in potential targets. Among the top 20 pathways, nine pathways were related to liver disease. Conclusion Sini Powder may play a protective role in liver by regulating potential targets such as IL-6, VEGFA, EGFR, PPARG, CASP3 and HIF-1, TNF, PI3 K-Akt and other related signaling pathways to exert the functions of anti-inflammation, anti-oxidative stress and inhibition of apoptosis in order to protect liver.