基于网络药理学分析苍术-桂枝治疗非酒精性脂肪性肝炎的作用机制

Analysis of the mechanism of herb pair containing Atractylodis Rhizoma and Cinnamomi Ramulus against nonalcoholic steatohepatitis on network pharmacology

目的网络药理学筛选苍术-桂枝治疗非酒精性脂肪性肝炎的有效成分和靶点。方法应用TCMSP和Swiss查找苍术、桂枝的活性成分的靶点,通过OMIM和GeneCards数据检索非酒精性脂肪性肝炎的靶点,获取交集靶点,利用Cytoscape 3.6.0构建苍术-桂枝与非酒精性脂肪性肝炎的“药物-成分-疾病-靶点”的网络图,筛选出关键靶点,进行GO和KEGG富集分析,最后利用分子对接验证关键靶点。结果得到苍术-桂枝有效活性成分16个,交集靶点77个,蛋白互作分析(PPI)得到ACE、APOB、CAT、TP53、EGFR、PPARG等16个核心靶点。KEGG和GO结果显示:主要影响脂质颗粒、细胞外间隙、内质网等10种细胞成分,脂肪酸结合、肝素结合、脂质转运体活性等10种分子功能,作用于炎症反应、胆固醇稳态、胆固醇代谢过程等10种生物过程,主要通过脂质与动脉粥样硬化、胰岛素抵抗、非酒精性脂肪肝等13种通路对非酒精性脂肪性肝炎起作用,分子对接结果证明,16中有效成分与靶点具有较强的结合能。结论苍术-桂枝改善非酒精性脂肪性肝炎的作用机制可能通过胰岛素抵抗、非酒精性脂肪肝等通路实现的,具有多个靶点,多个成分,多条通路的特点。

Objective The effective components and action targets of Atractylodis Rhizoma and Cinnamomi Ramulus can be screened using network pharmacology.Methods TCMSP and Swiss databases were used to search for active targets of A.Rhizama and C.Ramulus,and OMIM and GeneCards database used to search for targets of nonalcoholic steatohepatitis.A"drug-composition-disease targeting"network was constructed using Cytoscape software and protein-protein interaction network,to screen out key targets.Then,validate the results by molecular docking.Results There are 16 active ingredients and 383 targets for Atractylodis Rhizama and Cinnamomi Ramulus,656 nonalcoholic steatohepatitis targets and 77 intersecting targets of A.Rhizama-C.Ramulus and nonalcoholic steatohepatitis.Protein-protein 16 core targets of ACE,APOB,CATTP53,EGFR,PPARG were generated by PPI.Enrichment analysis revealed 10 cellular components,including lipid particle,macromolecular complex complexes and endoplasmic reticulum.10 biological processes such as fatty acid binding,lipid transporter activity,cholesterol homeostasis,cellular response to cholesterol metabolism,insulin secretion regulation,active regulation of inflammatory response.lipid and atherosclerosis,insulin resistance,non-alcoholic fatty liver disease,hepatocellular carcinoma etc.13 signal paths for nonalcoholic steatohepatitis′s treatment.Molecular docking proved that A.Rhizama-C.Ramulus has a strong binding ability to treat components and targets of nonalcoholic steatohepatitis.Conclusion The mechanism of action of A.Rhizama-C.Ramulus against nonalcoholic steatohepatitis may be realized through insulin resistance,steatosis,etc.Characterized by multi-targeting,multi-component,multi-channel synergism,and co-resistance to NASH.