基于网络药理学探究黄芪、红芪在益气活血通便方治疗慢传输型便秘中的作用机制差异

Exploring the Difference of Action Mechanism Between Astragalus Radix and Hedysari Radix in the Treatment of Slow Transit Constipation with Yiqi Huoxue Tongbian Decoction Based on Network Pharmacology

目的:在黄芪、红芪本草药用历史对比总结基础上,利用网络药理学探究黄芪、红芪在益气活血通便方治疗慢传输型便秘中的作用机制差异,利用分子对接进行验证。方法:利用TCMSP和PharmMapper数据库筛选益气活血通便方中当归、黄芪、肉苁蓉、火麻仁、红芪的活性成分及靶点;通过GeneCards、DrugBank、OMIM等数据库筛选慢传输型便秘相关靶点,利用Venny 2.1.0工具作图比较益气活血通便方Ⅰ和组方Ⅱ治疗慢传输型便秘的靶点;通过STRING数据库构建活性成分和关键靶点PPI网络;利用Metascape平台进行GO和KEGG通路富集分析,比较网络药理学差异。构建益气活血通便方的成分-靶点-通路网络图,利用AutoDock软件进行分子对接。结果:得到组方Ⅰ60个活性成分,501个作用靶点;组方Ⅱ50个活性成分,622个作用靶点。得到疾病作用靶点1035个,组方Ⅰ和组方Ⅱ与慢传输型便秘交集靶点分别为161个和201个。GO富集分析得到益气活血通便方Ⅰ553条生物进程或通路,组方Ⅱ899条生物进程或通路。KEGG富集分析预测组方Ⅰ126条信号通路,组方Ⅱ144条信号通路。分子对接结果显示槲皮素、木犀草素、花生酸、山柰酚、3,9-二-O-甲基尼森香豌豆紫檀酚与EGFR、SRC、CASP3、HSP90AA1、ESR1有良好的结合活性。结论:益气活血通便方通过多点显效、协同增效治疗慢传输型便秘,红芪可发挥与黄芪相似的作用,但能否替代黄芪还有待于结合药效学实验、临床试验进一步深入研究。

Objective:Based on the comparison and summary of the medicinal history of Astragalus Radix and Hedysari Radix,the differences in the mechanism of Astragalus Radix and Hedysari Radix in the treatment of slow transit constipation with Yiqi Huoxue Tongbian Decoction were explored by using network pharmacology,and verified by molecular docking.Methods:The active components and targets of Angelica sinensis,Astragalus Radix,Cistanche deserticola,Hemp seed and Hedysari Radix were screened using TCMSP and PharmMapper databases.Screen targets related to slow transit constipation through databases such as GeneCards,DrugBank,OMIM,etc.For the related targets of constipation,the Venny 2.1.0 tool was used to map and compare the targets of groupⅠand groupⅡin the treatment of STC;the PPI network map of related active ingredients and key targets was constructed through the STRING database;use Metascape platform to conduct GO and KEGG pathways enrichment analysis,Comparing the network pharmacological differences between groupⅠand groupⅡ,construct component-target-pathway network map of Yiqi Huoxue Tongbian Decoction,AutoDock software was used for molecular docking.Results:From the prediction results,a total of 60 active ingredients of groupⅠwere obtained,with 501 targets;50 active ingredients and 622 targets were found in groupⅡ.There were 1035 constipation-related targets,161 and 201 intersection targets of groupⅠand groupⅡwith STC.GO enrichment analysis revealed 553 biological processes or pathways in groupⅠ,and 899 biological processes or pathways in groupⅡ.KEGG enrichment analysis predicted 126 signaling pathways in groupⅠand 144 signaling pathways in groupⅡ.Molecular docking results showed quercetin,luteolin,arachidonic acid,kaempferol,and 3,9-di-O-methylnisenol have good binding activities to EGFR,SRC,CASP3,HSP90AA1,and ESR1.Conclusion:Yiqi Huoxue Tongbian Decoction can treat slow-transmission constipation through multi-point and synergistic effects.Hedysari Radix can play a similar role as Astragalus Radix,but whether it can replace Astragalus Radix still needs to be further studied in combination with pharmacodynamic and clinical experiments.