基于网络药理学和分子对接的半夏泻心汤治疗慢性萎缩性胃炎作用机制探讨

Mechanism of Banxia-Xiexin Decoction in treatment of chronic atrophic gastritis on network pharmacology and molecular docking

目的运用网络药理学方法研究半夏泻心汤治疗慢性萎缩性胃炎(CAG)的作用机制。方法运用中药系统药理学数据库和分析平台(TCMSP)获取半夏泻心汤化合物及靶标,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为阈值进行化合物筛选,将靶标输入Uniprot获取靶标对应的基因Symbol;从人类基因数据库(Gene Card:The Human Gene Database)获取CAG疾病基因,并筛选出与半夏泻心汤靶标基因的交集基因;运用Cytoscape3.7.1软件绘制"疾病-中药-化合物-交集靶标(基因)"网络图、STRING构建蛋白互作(PPI)网络、利用分子对接技术对关键靶点和化合物的相互作用进行验证。G∶Profiler数据分析平台进行GO富集以及KEGG通路富集分析。结果通过设置OB和DL值筛选得到半夏泻心汤化合物189种,在获得交集基因80个后,剔除不含交集基因(靶标)的化学成分后,最终筛得化合物148种,GO富集分析后共获得符合筛选标准的条目1188条,其中分子功能59条、生物过程1086条、细胞组成43条,KEGG富集分析共获得97条。槲皮素、黄芩素、汉黄芩素、小檗碱等为半夏泻心汤的主要活性成分,STAT3、TNF、AKT1、HSP90AA1、TP53等为主要作用靶标。分子对接结果显示,筛选的化合物和核心靶点HSP90AA1、潜在靶点EGFR之间均能较好的结合,涉及氮化合物的代谢、氧化反应、细胞凋亡等生物过程,调控PI3K-Akt信号通路、IL-17信号通路、胃癌通路、幽门螺旋杆菌感染的上皮细胞通路。结论半夏泻心汤的主要活性成分有槲皮素、黄芩素、汉黄芩素、小檗碱,通过多靶点多通路发挥治疗慢性萎缩性胃炎作用。

Objective To study on the mechanism of Banxia-Xiexin Decoction in the treatment of chronic atrophic gastritis on network pharmacology.Methods The compound and target of Banxia-Xiexin decoction were obtained by Traditional Chinese Medicine Systems Pharmacology(TCMSP)analysis platform database.The compound was screened by oral bioavailability(OB)≥30%and drug-like property(DL)≥0.18 as thresholds,and The target was input into Uniprot to obtain the gene Symbol;The disease target genes of chronic atrophic gastritis were obtained from Gene Card:The Human Gene Database,and screening intersection genes with Banxia-Xiexin decoction target genes;The network diagram of"disease-traditional Chinese medicine-compoundintersection target(gene)"was drawed by Cytoscape 3.7.1 software.The protein-protein interaction relationships were constructed by STRING database.Molecular docking technology were used to verify the interactions between core targets and compounds.GO enrichment and KEGG pathway enrichment were analyzed by g:Profiler data analysis platform.Results 189 compounds of BanxiaXiexin Decoction were screened by setting OB and DL values.After obtaintion of 80 intersection genes,148 compounds were finally screened by eliminating chemical components without intersection genes(targets).A total of 1188 items were screened through the GO enrichment analysis,including 59 molecular functions,1086 biological processes,43 cellular components.And 97 items were obtained by KEGG enrichment analysis.Quercetin,baicalein,wogonin and berberine are the main active components of Banxia Xiexin decoction.STAT3,TNF,AKT1,HSP90 AA1,TP53 are the main targets.The results of molecular docking showed that the screened compounds could bind well with the core target HSP90 AA1 and the potential target EGFR.The nitrogen metabolism,oxidation reaction,cell apoptosis and other biological processes are biological processes involved.PI3 K-Akt signal pathway,IL-17 signal pathway,gastric cancer pathway,epithelial cell signaling in helicobacter pylori infection pathway are main regulation pathways.Conclusions This study provide certain reference for further study on the mechanism of Banxia-Xiexin decoction in treating CAG.