基于网络药理学克银丸治疗银屑病作用机制的研究

Mechanism of Psoriasis Keyin Pill Based on Network Pharmacology

目的运用网络药理学方法探讨克银丸治疗银屑病的功效物质基础和作用机制。方法使用中药系统药理学分析平台(Traditional Chinese medicine systems phannacology,TCMSP)检索克银丸全方4味中药的活性化合物和作用靶点,通过Online Mendelian Inheritance in Man(OMIM)、Genecards、PharmGkb以及Therapeutic Target Database(TTD)数据库查找银屑病的相关靶点,构建“药物-共同靶点-疾病”网络图,针对克银丸和银屑病的共同靶点,构建蛋白互作网络(Protein-protein interaction network,PPI),进而完成Gene Ontology(GO)、Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析。结果以口服生物利用度(Oral bioavailability,OB)≥30%且类药性(Drug likeness,DL)≥0.2为标准,筛选出克银丸的活性化合物共有42种,作用靶点有73个;以高相关性为标准,筛选出银屑病的高关联度靶点一共有1081个,药物与疾病的共同靶点一共有46个。构建蛋白互作网络(PPI),分析共同靶点之间的相互关系最多的靶点为白细胞介素(IL)-6、血管内皮生长因子(VEGF)A、表皮生长因子受体(EGFR)、重组人半胱天冬酶(CASP)-3、细胞周期蛋白(CCN)D1。GO富集分析共包含658条结果,显示共同靶点的功能主要表现在对氧感知相关通路,KEGG信号通路富集显示,共同靶点表达在112条信号通路中。结论以网络药理学为切入点,阐明了克银丸是通过多成分、多靶点发挥对银屑病的治疗作用,且作用机制主要集中在对氧感知相关通路的调控,为克银丸的临床应用和实验研究提供了科学依据。

Objective In order to study the effective substance basis and mechanism of Keyin pill in the treatment of psoriasis by network pharmacology.Methods Active compounds and targets related to the four traditional Chinese medicine(TCM)were searched through the TCM systems phannacology(TCMSP)database and analysis platform.Through Online Mendelian Inheritance in Man(OMIM),Genecards,PharmGkb and therapeutic target database(TTD)searched for relevant targets of psoriasis and built"drug-common targets-disease"network diagram.In view of the common targets between Keyin pill and psoriasis constructed PPI network,and then completed the Gene Ontology(GO),Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis.Results Selecting the oral bioavailability(OB)greater than or equal to 30%and DL greater than or equal to 0.2 as filter condition,42 active ingredients and 155 targets were screened from Keyin pill.With high correlation as the standard,a total of 1081 high correlation targets of psoriasis and 46 common targets of drugs and diseases were screened out.PPI network was constructed,and then the most common targets were IL-6,VEGFA,EGFR,CASP3 and CCND1.A total of 658 results were included in the GO enrichment analysis,indicating that the function of the common target was mainly manifested in the oxygen-sensing related pathway.The KEGG signal pathway enrichment showed that the common target was expressed in 112 signal pathways.Conclusion Taking network pharmacology as the starting point,it is clarified that Keyin pill plays a therapeutic role on psoriasis through multiple components and multiple targets,and the mechanism of action mainly focuses on the regulation of oxygen perception related pathways,which provides scientific basis for the clinical application and experimental research of Keyin pill.