基于网络药理学和分子对接技术探讨“黄芪-海风藤”治疗紫癜性肾炎的作用机制

Exploration of the mechanism of“Huangqi-Haifengteng”in the treatment of henoch-schonlein purpura nephritis by network pharmacology and molecular docking

目的:基于补气通络法运用网络药理学方法和分子对接技术探讨“黄芪-海风藤”药对治疗紫癜性肾炎(HSPN)的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)分别检索黄芪和海风藤的活性成分及药物靶点,通过GeneCards、DisGeNET数据库查找HSPN的疾病靶点,取活性成分与疾病的交集靶点,运用Cytoscape软件构建活性成分-交集基因靶点PPI网络;经DAVID数据库分析进行GO功能和KEGG通路富集分析,运用AutoDock软件对关键活性成分与核心靶点进行分子对接。结果:筛选出黄芪活性成分10个,海风藤活性成分18个,作用靶点205个,HSPN疾病靶点795个,药物与HSPN共同靶点基因73个;GO功能分析涉及凋亡过程的负反馈、肿瘤坏死因子受体结合等调控,KEGG通路富集分析涉及肿瘤坏死因子(TNF)、白细胞介素-17(IL-17)等信号通路。分子对接显示连接度排名前4位的药对活性成分槲皮素、豆甾醇、海风藤酮与关键核心靶点基质金属肽酶-9(MMP-9)、TNF、肿瘤蛋白P53(TP53)具有较好的结合活性。结论:研究初步验证“黄芪-海风藤”治疗HSPN作用机制,并为进一步研究提供科学依据。

Objective:To explore the mechanism of couplet medicines of“Huangqi-Haifengteng”in the treatment of henoch-schonlein purpura nephritis(HSPN)by network pharmacology and molecular docking based on the method of tonifying Qi and dredging collaterals.Methods:The active ingredients and drug targets of Huangqi and Haifengteng were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and then the disease targets of HSPN were searched through GeneCards and DisGeNET databases.Then the intersection targets of active ingredients and diseases were selected.Cytoscape software was used to construct the PPI network of active ingredients-intersection gene targets,and DAVID database was used for gene function GO and KEGG pathway enrichment analysis.Autodock software was used to perform molecular docking between key active ingredients and core targets.Re⁃sults:Ten active ingredients of Huangqi and 18 active ingredients of Haifengteng were screened.205 effect targets and 795 targets of HSPN disease were identified.There were 73 common target genes between drugs and HSPN.GO functional analysis involved the regulation of negative feedback of apoptosis process and tumor necrosis factor receptor binding,and KEGG pathway enrichment analysis involved tumor necrosis factor(TNF)and interleukin-17(IL-17)signaling pathways.Molecular docking showed that the active ingredients quercetin,stigmasterol,and kadsurenone in the top four couplet drugs with the highest connectivity had good binding activity to the key core targets matrix metallopeptidase-9(MMP-9),TNF,and tumor protein P53(TP53).Conclusion:This study preliminarily verifies the mechanism of“Huangqi-Haifengteng”in the treatment of HSPN,and provides scientific basis for further research.