基于网络药理学和分子对接探讨青黛防治2型糖尿病的作用机制研究

Action mechanism of Indigo Naturalis in the prevention and treatment of diabetes mellitus type 2 based on network pharmacology and molecular docking

目的:通过网络药理学和分子对接初步揭示了青黛抗2型糖尿病的作用机制。方法:从中药系统药理学数据库与分析平台(TCMSP)中根据吸收和代谢情况选出青黛的有效成分及成分所对应的靶点,将靶点转换成对应的基因,取青黛和2型糖尿病的交集基因做PPI蛋白互作网络图,通过David数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)分析,最后采用分子对接验证。结果:筛选得到青黛的活性成分9个、交集基因204个,通过蛋白互作分析发现“STAT3、JUN、MAPK3”可能有治疗2型糖尿病的作用,KEGG富集发现,且可能通过positive regulation of transcription from RNA polymerase II promotor、response to drug、positive regulation of gene expression等信号通路进行调控。分子对接结果表明青黛中的Bisindigotin、Indican、Isovitexin等活性成分与“STAT3、JUN、MAPK3”有比较强的结合能力。结论:青黛可能是通过Bisindigotin、Indican、Isovitexin等成分调控positive regulation of transcription from RNA polymerase II promotor等相关信号通路上的STAT3、JUN、MAPK3等基因发挥治疗2型糖尿病的作用。

This study preliminarily reveals the action mechanism of Indigo Naturalis in the prevention and treatment of diabetes mellitus type 2 based on network pharmacology and molecular docking.From the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),the active ingredients of Indigo Naturalis and their corresponding targets were selected according to their absorption and metabolism,and the targets were converted into corresponding genes.The PPI protein interaction network was obtained based on the intersecting genes of Indigo Naturalis and diabetes mellitus type 2.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis was carried out by using the David database,and finally verified by molecular docking.Nine active ingredients and 204 intersecting genes of Indigo Naturalis were screened out.The protein interaction analysis found that STAT3,JUN,and MAPK3 had the potential effect of treating diabetes mellitus type 2.KEGG enrichment found that the regulation might be realized through positive regulation of transcription from RNA polymerase II promotor,response to drug,positive regulation of gene expression,and other signaling pathways.Molecular docking results showed that Bisindigotin,Indican,Isovitexin and other active components in Indigo Naturalis had very strong binding ability with STAT3,JUN,and MAPK3.In conclusion,Indigo Naturalis might play a role in the treatment of diabetes mellitus type 2 by regulating STAT3,JUN,MAPK3 and other genes in related signaling pathways such as positive regulation of transcription from RNA polymerase II promotor through Bisindigotin,Indican,Isovitexin and other components.