摘要
目的基于网络药理学及分子对接初步探讨四妙丸治疗痛风的作用机制。方法通过中药系统药理数据库和分析平台(TCMSP)和中药分子机制的生物信息学在线分析工具(BATMAN-TCM)数据库筛选四妙丸所含的活性化合物及作用靶点;检索GeneCards数据库获取痛风相关的疾病靶点;将药物和疾病靶点导入Bioinformatics & Evolutionary Genomics取交集,即药物(四妙丸)与疾病(痛风)的共同靶点,并利用Cytoscape 3.7.1软件构建四妙丸-化合物-靶点-痛风网络图;通过STRING数据库和R软件分别绘制PPI网络图和进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析;另外选取部分化合物和靶点通过MOE软件进行分子对接验证;最后通过单钠尿酸盐(MSU)结晶诱导人髓系白血病单核细胞(THP-1)复制痛风细胞模型以进一步验证上述结果。结果本研究共筛选出四妙丸相关活性化合物65个,药物相关靶点724个,四妙丸与痛风的共同靶点20个;网络图提示槲皮素和山柰酚,环加氧酶 1(PTGS1)可能分别是四妙丸治疗痛风的有效化合物和靶点;GO富集分析提示四妙丸治疗痛风主要与转录辅因子、转录因子、增强子、肌动蛋白、核转录因子(NF-κB)等有关;KEGG富集分析显示四妙丸可能通过AGE-RAGE、NF-κB、MAPK8和TNF等多条信号通路治疗痛风;分子对接结果显示槲皮素、山柰酚、汉黄芩素、小檗碱与MAPK8有良好对接活性;细胞实验结果表明,槲皮素能够抑制MSU诱导THP-1细胞后MAPK8蛋白的表达。结论四妙丸治疗痛风呈现多分子、多靶点、多通路的协同作用机制,为后续深入探讨四妙丸治疗痛风的分子机制提供理论依据。
Objective To explore the mechanism of Simiao pills(SM)for gout based on network pharmacology and molecular docking technique.Methods The active compounds and related targets of SM were obtained from TCMSP and BATMAN-TCM databases,and the gout-related targets were identified from GeneCards database.The targets of drugs and diseases were submitted into Bioinformatics&Evolutionary Genomics database to obtain the common targets of the drug(SM)and the disease(gout).Cytoscape 3.7.1 and STRING database were used to construct SM-compound-target-gout network and PPI network respectively.The GO and KEGG enrichment analysis were conducted by R software.Moreover,MOE software was applied to validate the compound-target association.Finally,an in vitro model of gout was used to further validate the results.Results Totally 65 active compounds and 724 SM targets were collected,and 20 shared targets of SM and gout were obtained.The network analysis indicated that quercetin,kaempferol,and PTGS1 were the active compounds and targets of SM in treatment of gout.GO enrichment analysis indicated that transcription cofactor,transcription factor,enhancer,actinin,and NF-κB might involve in the SM treatment for gout.KEGG enrichment analysis predicated that 79 signal pathways might involve in the treatment of gout with SM,including AGE-RAGE,NF-κB,MAPK8 and TNF signal pathways.The molecular docking showed that quercetin,kaempferol,wogonin and berberine had good docking activity with MAPK8.Furthermore,in vitro experiments clearly showed that quercetin inhibited the expression of MAPK8 in the THP-1 cells induced by MUS.Conclusion Bioinformatic analyses suggest that the mechanism of SM treatment for gout is characterized by the co-synergism of multi-components,multi-targets,and multi-pathways,which provides a theoretical basis for further studies.
作者
吴源陶
邹译娴
张春虎
冯君
WU Yuan-tao;ZOU Yi-xian;ZHANG Chun-hu;FENG Jun(The First Hospital of Hunan University of Chinese Medicine,Changsha 410007;Xiangya Hospital,Central South University,Changsha 410008)
出处
《中南药学》
CAS
2020年第7期1120-1126,共7页
Central South Pharmacy
基金
国家自然科学基金资助项目(No.81673951)。
关键词
四妙丸
痛风
网络药理学
分子对接
槲皮素
Simiao pill
gout
network pharmacology
molecular docking
quercetin
