基于网络药理学和分子对接探讨“黄芪-黄连”药对治疗儿童肥胖症的作用机制

Discussion on Mechanism of“Astragalus-Coptis”in Treating Childhood Obesity Based on Network Pharmacology and Molecular Docking

目的基于网络药理学和分子对接探讨“黄芪-黄连”药对治疗儿童肥胖病的作用机制。方法首先利用(中药系统药理学数据库与分析平台)TCMSP数据库,对黄芪、黄连的活性成分进行挖掘。利用UniProt数据库对靶点进行校正。再以儿童肥胖病(childhood obesity)为查找条件,通过Gene Cards、OMIO数据库筛选儿童肥胖病的相关靶点,并与“黄芪-黄连”药对的作用靶点进行选取交集处理,得到该药对治疗儿童肥胖病的有效靶点。利用String数据库对上述靶点进行蛋白质-蛋白质相互作用(PPI)网络预测,之后利用Bioconductor数据库进行GO和KEGG富集分析,最后利用AutoDock软件对度值较高的药物成分和核心靶点进行分子对接验证。结果共筛选出“黄芪-黄连”药对67个药物活性成分及95个治疗儿童肥胖病的靶点。通过PPI网络分析,“黄芪-黄连”药对治疗儿童肥胖病可能与MAPK8、EGFR、IL6、ESR1、VEGFA、CCND1、AR、MYC、CASP3、PPARG等蛋白靶点有关。GO功能富集分析显示“黄芪-黄连”药对的主要功能为蛋白质异源二聚化、近端启动子序列特异性DNA结合、RNA聚合酶Ⅱ近端启动子序列特异性DNA结合、染色质结合、泛素样蛋白连接酶结合等;KEGG通路分析涉及的主要通路为PI3K/Akt、MAPK信号通路、卡波西肉瘤相关疱疹病毒、人巨细胞病毒感染等。分子对接表明“黄芪-黄连”药对的主要活性成分与疾病的核心靶点有较稳定的结合活性。结论“黄芪-黄连”药对可直接或间接作用于PI3K/Akt通路,主要通过调节细胞分裂、抑制炎症等治疗儿童肥胖症。

Objective To explore the mechanism of“Astragalus-Coptis”medicine on the treatment of childhood obesity based on network pharmacology and molecular docking.Methods The TCMSP database was used to excavate the active components of Astragalus and Coptis.The UniProt database was used to correct the official gene names of the targets of“Astragalus-Coptis”medicine.Under the condition of childhood obesity,the relevant targets of childhood obesity were obtained through the GeneCards database and the OMIO database,and selected and intersected with the active targets of“Astragalus-Coptis”medicine,then the effective targets of“Astragalus-Coptis”medicine for the treatment of childhood obesity were obtained.The above targets were input into the String database for protein-protein interaction(PPI)network prediction,then treated with the Bioconductor database for GO and KEGG enrichment analysis.Finally,the verification of molecular docking were performed with AutoDock software for drug components and core targets with high degree value.Results A total of 67 active ingredients of“Astragalus-Coptis”medicine and 95 targets for the treatment of childhood obesity were screened out.Through PPI network analysis,the treatment of childhood obesity with“Astragalus-Coptis”medicine might be related to the protein targets such as MAPK8,EGFR,IL6,ESR1,VEGFA,CCND1,AR,MYC,CASP3,PPARG.The GO enrichment analysis indicated that the main functions“Astragalus-Coptis”medicine included the protein heterodimerization activity,the proximal promoter sequence-specific DNA binding,the RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding,the chromatin binding and the ubiquitin-like protein ligase binding.The main pathways involved in the KEGG pathway analysis were PI3K/Akt signaling pathway,Kaposi sarcoma-associated herpesvirus infection,human cytomegalovirus infection,MAPK signaling pathway,etc.Molecular docking showed that the main active components of“Astragalus-Coptis”medicine had stable binding activity with the core targets of the disease.Conclusion“Astragalus-Coptis”medicine can directly or indirectly act on PI3K/Akt pathway,and treat childhood obesity mainly by regulating cell division and inhibiting inflammation.