基于网络药理学探讨红花-黄芪治疗原发性胆汁性胆管炎的可能性

To explore the possibility of safflower-astragalus in treating primary biliary cirrhosis based on network pharmacology

目的:利用网络药理学方法探讨红花-黄芪治疗原发性胆汁性胆管炎的可能性。方法:应用中药系统药理学数据库与分析平台搜索“红花”、“黄芪”得到其有效成分及作用靶点,利用GeneCards数据库和OMIM数据库获取原发性胆汁性胆管炎的疾病靶点。将红花、黄芪的作用靶点与原发性胆汁性胆管炎的靶基因取交集得到共同的靶基因,利用Cytoscape3.8.0绘制红花-黄芪与原发性胆汁性胆管炎的成分-靶点网络图;利用String平台构建蛋白质-蛋白质相互作用网络并进行基因本体功能富集分析和京都基因与基因组百科全书通路富集分析。结果:筛选得到红花-黄芪与原发性胆汁性胆管炎的交集靶基因81个,以槲皮素、木犀草素和山萘酚3种有效成分作用靶点较多,主要作用于疾病的前列腺素-环氧合酶1、丝氨酸蛋白酶1和雄激素受体等靶点,蛋白互作网络分析主要核心靶点有白蛋白、白介素6和丝裂原活化蛋白激酶8,主要涉及DNA结合转录激活因子活性/RNA聚合酶Ⅱ特异性的生物过程,主要涉及前列腺癌、乙型肝炎和卡波西肉瘤相关疱疹病毒感染等信号通路。结论:基于网络药理学分析显示红花-黄芪可能通过多成分、多靶点、多途径达到治疗原发性胆汁性胆管炎的作用。

Objective:To explore the possibility of using network pharmacology to treat primary biliary cirrhosis by using safflower and astragalus.Methods:Traditional Chinese medicine systems pharmacology database and analysis platform were used to search for"Safflower"and"Astragalus"to obtain their ingredients and targets.Using GeneCards database and OMIM database to obtain disease targets of primary biliary cirrhosis.The targets of safflower and astragalus were intersected with the targets of primary biliary cirrhosis to obtain the common target genes,and Cytoscape3.8.0 was used to draw the components-target network map of safflower-astragalus and primary biliary cirrhosis.A protein-protein interaction network was constructed using string platform and gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes pathway enrichment analysis were carried out.Results:Eighty-one target genes of the intersection of safflower-astragalus and primary biliary cirrhosis were screened.There were many targets of quercetin,luteolin and kaempferol,mainly acting on prostaglandin-endoperoxide synthase 1(PTGS1),serine protease 1(PRSS1)and androgen receptor(AR).The main core targets of protein interaction network analysis were albumin(ALB),interleukin 6(IL 6)and mitogen-activated protein kinase 8(MAPK8).And it was mainly involved in DNA-binding transcription activator activity/RNA polymerase II-specific biological processes,and was mainly involved in signaling pathways such as prostate cancer,hepatitis B and kaposi sarcoma-associated herpes virus infection.Conclusion:Based on the network pharmacology analysis,it was shown that safflower-astragalus may achieve the effect of treating primary biliary cirrhosis by multi-component,multi-target and multi-way.