桂枝-白芍治疗慢性心力衰竭作用机制的网络药理学分析

Network Pharmacological Analysis of Mechanism of Cinnamomum Cassia-Radix Paeoniae Alba in Treating Chronic Heart Failure

目的基于网络药理学分析桂枝-白芍治疗慢性心力衰竭(chronic heart failure,CHF)的作用机制。方法进入TCMSP数据库以桂枝、白芍为检索词,口服生物利用度(oral bioavailability,OB)≥30%和类药性(drug like,DL)≥0.18为筛选条件获取有效成分与靶蛋白。运用GeneCards、OMIM、PharmGkb、TTD、DrugBank等数据库获得CHF相关蛋白;取疾病相关的蛋白与药物靶蛋白的交集,并导入string数据库获得蛋白互作关系。借助Cytoscapev 3.8.2软件进行药物-疾病拓扑分析。通过Rx644.0.2获得GO和KEGG富集分析结果。最后通过AutoDock Vina对重要化合物作分子对接验证。结果得到中药潜在活性成分20个,主要为紫杉醇、表儿茶素、芍药苷、山柰酚、β-谷甾醇等。核心靶点8个,包括肿瘤坏死因子(tumor necrosis factor,TNF)、芳香烃受体(Aryl hydrocarbon receptor,AHR)、半胱氨酸天冬氨酸蛋白酶(Caspase,CASP)3、白细胞介素(Interleukin,IL)-6等。基因富集分析得到1849条GO功能条目和150条KEGG通路。分子对接结果显示,有效成分和靶蛋白间的亲和力均<-5 kJ/mol。结论桂枝-白芍治疗CHF的机制可能是通过紫杉醇、表儿茶素、芍药苷、山柰酚、β-谷甾醇等多种有效成分调控TNF、AHR、CASP3、IL-6、细胞间黏附分子(Intercellular adhesion molecule,ICAM)1、RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、前列腺素G/H合酶(Prostaglandin G/H synthase,PTGS)2、转录因子AP-1(Transcription factor AP-1,JUN)等核心蛋白以及细胞凋亡通路、Th17细胞分化通路、NF-κB信号通路、IL-17信号通路等信号通路,进而抑制心肌细胞凋亡、心肌纤维化、氧化应激以及炎症反应的发生。

Objective To analyze the mechanism of Cinnamomum Cassia-Radix Paeoniae Alba drug pair in treating chronic heart failure based on network pharmacology analysis.Methods the effective components and target proteins were obtained by entering TCMSP database,taking Cinnamomi Ramulus and Paeoniae Radix Alba as search words,oral bioavailability(OB)≥30%and drug like(DL)≥0.18 as screening conditions.Chronic heart failure related proteins were obtained by genecards,OMIM,PharmGkb,TTD,DrugBank,and other databases.The intersection of disease-related proteins and drug target proteins was taken and imported into the string database to obtain the protein interaction relationship;Drug disease topology analysis with the help of cytoscapev 3.8.2 software.Go and KEGG enrichment analysis results were obtained by Rx644.0.2.Finally,the molecular docking of important compounds were verified by autodock Vina.Results 20 potentially active components of traditional Chinese medicine were obtained,mainly paclitaxel,epicatechin,paeoniflorin,kaempferol,and sitosterol.8 core targets,including TNF,AHR,CASP3,IL-6,etc.1849 go functional items and 150 KEGG pathways were obtained by gene enrichment analysis.The results of molecular docking showed that the affinity between active components and target proteins was less than-5 kJ/mol.Conclusion the mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair in the treatment of CHF may be through paclitaxel,epicatechin,paeoniflorin,kaempferol,β-Sitosterol,and other active ingredients regulate core proteins such as TNF,AHR,CASP3,IL-6,ICAM1,AKT1,PTGS2,and Jun,as well as apoptosis pathway.Th17 cell differentiation pathway and NF-κB signaling pathway.IL-17 signaling pathway and other signaling pathways can inhibit cardiomyocyte apoptosis,myocardial fibrosis,oxidative stress,and inflammatory response.