基于网络药理学方法分析当归-川芎药对治疗骨关节炎的潜在靶点和机制

Analysis of potential targets and mechanism of Danggui-Chuanxiong herb pair for treatment of osteoarthritis using network pharmacology approach

目的:探讨当归-川芎药对治疗骨关节炎(osteoarthritis,OA)的作用靶点和机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索、筛选当归和川芎的活性成分及作用靶点。在GeneCards数据库检索OA的相关基因,通过R软件与当归、川芎的作用靶点相交叠,筛选当归-川芎药对治疗OA的关键靶点。分别利用Cytoscape软件和STRING数据库构建药物-成分-靶点-疾病网络和关键靶点蛋白相互作用网络。最后利用R软件进行关键靶点基因GO功能富集分析与KEGG通路富集分析。结果:共筛选出当归-川芎药对的9个活性成分及对应的29个关键靶点。建立的药物-成分-靶点-疾病网络共包含36个节点、71条边,当归的2个活性成分对应15个靶点,川芎的7个活性成分对应14个靶点。建立的靶点蛋白相互作用网络包含25个节点、102条边,其中的关键靶点蛋白包括半胱氨酸蛋白酶3(caspase 3,CASP3)、JUN、雌激素受体1(estrogen receptor alpha,ESR1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)、丝裂原活化蛋白激酶14(mitogen-activated protein kinase 14,MAPK14)。GO功能富集分析与KEGG通路富集分析显示,当归-川芎药对治疗OA关键靶点基因的生物学过程和功能主要集中在核受体功能、转录因子活性、类固醇激素受体活性、固醇类激素结合、细胞凋亡等,相关的信号通路主要包括Apoptosis-multiple species信号通路、白细胞介素17信号通路、血管内皮生长因子信号通路、p53信号通路等。结论:当归-川芎药对治疗OA具有多成分-多靶点-多途径的特点,可能通过CASP3、JUN、ESR1、PTGS2、MAPK14等靶点及Apoptosis-multiple species、白细胞介素17、血管内皮生长因子、p53等信号通路发挥治疗作用。

Objective:To explore the action targets and mechanism of Danggui-Chuanxiong(DG-CX)herb pair for treatment of osteoarthritis(OA).Methods:The active ingredients and action targets of Danggui and Chuanxiong were screened by retrieving Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The OA-related genes were searched out from GeneCards databases,and the key targets of DG-CX herb pair for treatment of OA were selected out through overlapping OA-related genes with action targets of Danggui and Chuanxiong respectively using R software.The drug-ingredient-target-disease network was built by using Cytoscape software,and the network of interaction between key target proteins was built by using STRING database.GO function and KEGG pathway enrichment analysis were performed on key target proteins respectively by using R software.Results:Nine active ingredients and 29 corresponding key targets of DG-CX herb pair were selected out.The drug-ingredient-target-disease network diagram consists of 36 nodes and 71 edges in total,in which the 2 active ingredients of Danggui corresponded to 15 targets and the 7 active ingredients of Chuanxiong corresponded to 14 targets.The network of interaction between target proteins consists of 25 nodes and 102 edges in total,in which the key target proteins included caspase 3(CASP3),JUN,estrogen receptor alpha(ESR1),prostaglandin-endoperoxide synthase 2(PTGS2)and mitogen-activated protein kinase 14(MAPK14).The results of GO function and KEGG pathway enrichment analysis demonstrated that the biological processes and functions of key target genes of DG-CX herb pair for treatment of OA were mainly concentrated in nuclear receptor function,transcription factor activity,steroid hormone receptor activity,steroid hormone bind and cell apoptosis;and the related signal pathways consisted of apoptosis-multiple species signal pathway,interleukin-17(IL-17)signal pathway,vascular endothelial growth factor(VEGF)signal pathway and p53 signal pathway.Conclusion:The DG-CX herb pair has the characteristics of multiple ingredients,multiple targets and multiple pathways in treatment of OA,and it may produce the therapeutic effects through the targets including CASP3,JUN,ESR1,PTGS2 and MAPK14 and the signal pathways including Apoptosis-multiple species,IL-17,VEGF and p53 signal pathway.