基于网络药理学分析关节康片组药“红花-独活-羌活”治疗骨关节炎分子作用机制研究

Molecular Mechanism Analysis of Osteoarthritis Treated by“Honghua(Flos Carthami)-Duhuo(Radix Angelicae Pubescentis)-Qianghuo(Rhizoma Et Radix Notopterygii)”Drug Combination of Guangjiekang Capsule(关节康片)Based on Network Pharmacology and Bioinformatics

目的运用网络药理学方法探讨关节康片组药"红花-独活-羌活"在骨关节治疗中的分子作用机制。方法从中药药理学数据库TCMSP平台对关节康组药"红花-独活-羌活"进行中药活性成分筛选,依据口服生物利用度(OB)≥30%、类药性(DL)≥0.18对中药有效成分进行筛选,并获得相应基因名,使用Cytoscape_3.7.2软件对组药"红花-独活-羌活"进行活性成分-靶点基因网络图构建。通过DrugBank、GeneCards、Omim数据库以及TTD数据库对疾病靶点进行获取。随后对药物疾病靶点取交集,把共有靶点输入STRING数据库中,将表格数据导入数据可视化处理软件Cytoscape_v3.7.2中,进行PPI网络构建及关键靶点筛选。将有效核心化合物与相应核心靶点通过SWISS DOCK数据库进行虚拟分子对接,使用Metascape数据库对疾病-药物共同靶点进行GO-BP生物学过程分析和KEGG靶点通路富集分析。结果通过ADME参数设置共筛选出中药有效活性成分38个;共收集疾病靶点534个,去重后共获得药物-疾病共有靶点60个;分子对接结果显示,有效核心化合物与相应核心靶点结合紧密;通过GO-BP分析发现生物过程主要富集在细胞分化、迁移、细胞凋亡、细胞对生物的应激反应等方面;通过KEGG通路富集分析,共获得121条通路,通路主要涉及在免疫应答、糖代谢、炎症反应、肿瘤途径等方面。结论本研究通过网络药理学对关节康片组药"红花-独活-羌活"与骨关节炎进行成分、靶点、通路的分析可以看出,药物在骨关节炎的治疗中并非是简单的单一靶向性治疗,而是通过多成分、多途径、多靶点间的相互联系,共同作用产生的复杂机制,对骨关节炎未来的治疗上,在临床用药、配伍等相关方面提供了新的思路和分子机制层面的参考。

Objective To explore the potential molecular mechanism concerning herb compositions of“Honghua(Flos Carthami)-Duhuo(Radix Angelicae Pubescentis)-Qianghuo(Rhizoma Et Radix Notopterygii)”contained in Guangjiekang Capsule(关节康片)in the treatment of osteoarthritis by applying for network pharmacology.Methods The active components of traditional Chinese medicine“Honghua(Flos Carthami)-Duhuo(Radix Angelicae Pubescentis)-Qianghuo(Rhizoma Et Radix Notopterygii)”were screened from TCMSP platform of traditional Chinese medicine pharmacology database.The active components of traditional Chinese medicine were screened according to OB≥30%and DL≥0.18,and the corresponding gene names were obtained.Cytoscape_v3.7.2 software was used to construct the active ingredient target gene network diagram of“Honghua(Flos Carthami)-Duhuo(Radix Angelicae Pubescentis)-Qianghuo(Rhizoma Et Radix Notopterygii)”.The disease targets were obtained through DrugBank,GeneCards,OMIM database and TTD database.Then the intersection of drug disease targets were selected and the common targets were put into the STRING database,and the tabular data was imported into the data visualization processing software Cytoscape_v3.7.2.PPI network construction and key target screening were carried out.The effective core compounds were connected with the corresponding core targets through the SWISS DOCK database for virtual molecular docking,and the Metascape database was used for GO-BP biological process analysis and KEGG target pathway enrichment analysis of the common disease drug targets.Results A total of 38 active ingredients were screened through ADME parameter setting.534 disease targets and 60 drug targets were obtained after the repeated values were removed.The molecular docking results showed that the effective core compounds bound closely to the corresponding core targets.Biological processes analysis demonstrated the main enrichment consisting cell differentiation,migration,apoptosis,and stress response of cells to organisms.In terms of KEGG pathway enrichment analysis,a total of 121 pathways were obtained,which were mainly involved in immune response,glucose metabolism,inflammatory response,tumor pathway and other aspects.Conclusion Guangjiekang Capsule in the treatment of osteoarthritis is not a simple single targeted therapy,but by many compositions,ways and targets contacting each other to produce a integrated mechanism and enlarge the curative effect of single herb,which shed the light on the new medication of this disease.