摘要
目的:分析畲药"十二时辰"治疗类风湿性关节炎(Rheumatoid Arthritis,RA)的有效成分及可能作用机制。方法:通过文献挖掘并利用TCMSP等数据库获取畲药"十二时辰"的已知化学成分和相关靶点;将获得的靶点信息与Drug Bank数据库中抗RA药物靶点进行映射,分析药物治疗RA的可能性;利用Cytoscape软件分别构建"成分-靶点"网络和"十二时辰抗RA靶点-人体蛋白"蛋白质互作(PPI)网络,分析网络拓扑结构;利用David数据库进行GO富集和KEGG分析,分析药物治疗RA的可能分子机制。结果:畲药"十二时辰"含有油酸、棕榈酸、齐墩果酸、十五烷酸等潜在抗RA化合物,潜在抗RA关键靶点为前列腺素G/H合成酶1、2和凋亡调节因子Bcl-2等;GO结果提示其治疗RA的基因功能主要体现在炎症反应、凋亡过程负调节、NF-κB转录因子活性正调节、蛋白质同源二聚化活性等方面;KEGG结果暗示主要相关信号通路有TNF、PI3K-Akt、Rheumatoid arthritis、Toll样受体和MAPK等信号通路。结论:畲药"十二时辰"可能通过多靶点、多信号途径的相互作用,抑制成纤维样滑膜细胞的异常增殖,减轻炎症反应,发挥治疗RA的作用。
Objective To analysis the active compounds and possible mechanismsof She medicine Clematis florida Thunb.var.plena D.Don in the treatment of rheumatoid arthritis(RA).Methods Through the literature mining and using the TCMSP database,the known chemical compounds and related targets of Clematis florida Thunb.var.plena D.Don were obtained.Then,the targets of FDA-approved anti-RA drugs and the human protein interaction data were obtained from database of Drug Bank and HPRD,respectively.Cytoscape software was used to establish chemical compounds-targetnetwork and anti-RA targets of Clematis florida Thunb.var.plena D.Don-human protein PPInetwork,which were analysised network topology.The David database was used for GO enrichment and KEGG analysis to analyze the possible molecular mechanisms.Result She medicine Clematis florida Thunb.var.plena D.Don contained potential anti-RA compounds such as oleic acid,palmitic acid,oleanolic acid and pentadecanoic acid.Potential targets for this effect were prostaglandin G/H synthase 1(COX-1),prostaglandin G/H synthetase 2(COX-2) and apoptosis regulator Bcl-2.The GOenrichmentresults suggested that the gene function of anti-RA was mainly reflected in inflammatory response,negative regulation of apoptotic process,positive regulation of NF-kappa B transcription factoractivity and protein homodimerization activity.The results of KEGG analysis showed that the drug-resistant RA-related signaling pathway were mainly TNFsignaling pathway,PI3 K-Aktsignaling pathway,rheumatoid arthritis signaling pathway,Toll-like receptorssignaling pathway,MAPK signaling pathway and so on.Conclusion Our results indicated that active compoundsin Clematis florida Thunb.var.plena D.Donmight interact synergistically with multiple targets and signaling pathways to inhibitabnormal proliferation of fibroblast-like synoviocytes,reduce inflammatory responses,and treat rheumatoid arthritis.
作者
曾熙颖
张云
左春兰
林凡
ZENG Xiying;ZHANG Yun;ZUO Chunlan;LIN Fan(College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Department of Science Research,Fujian Institute of Education,FuZhou 350025,China;Fujian Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)
出处
《中国民族民间医药》
2020年第14期38-46,共9页
Chinese Journal of Ethnomedicine and Ethnopharmacy
基金
福建省大学生创新创业训练计划项目(201810393028)。
关键词
畲药“十二时辰”
类风湿性关节炎
网络药理学
作用机制
She Medicine Clematis florida Thunb.var.plena D.Don
Rheumatoid Arthritis
Network Pharmacology
Action Mechanism