基于网络药理学探究当归补血汤治疗骨质疏松症的分子作用机制

A network pharmacology approach to uncover the molecular mechanism of Dangguibuxue Decoction in the treatment of osteoporosis

目的基于系统网络药理学方法探讨当归补血汤治疗骨质疏松(OP)的分子作用机制。方法通过TCMSP平台筛选当归补血汤主要化学成分、对应靶点及靶标基因,借助Gene Cards数据库获取OP已知的相关靶点,将药物靶基因映射到疾病靶基因获得当归补血汤作用于OP的预测靶点;利用Cytoscape 3.5.1软件构建有效活性化合物-疾病靶点网络图以及STRING数据库绘制PPI网络,最后借用R 3.6.3软件进行关键蛋白分析,GO功能分析和KEGG通路富集分析。结果获得当归补血汤有效活性化学成分共17个,关键成分7个,药物作用于疾病的交集靶点130个,关键靶点30个;GO功能分析揭示当归补血汤治疗OP涉及生物功能主要有核受体活性、配体转录因子活性、调控序列特异性DNA结合、类固醇激素受体活性、细胞因子受体结合、细胞因子活性等;KEGG富集结果显示与糖尿病并发症中的AGE-RAGE信号通路、IL-17信号通路、乙型肝炎、前列腺癌、TNF信号通路等密切相关。结论本研究体现当归补血汤能通过多成分、多靶点、多通路作用于OP,可能与其发挥抗氧化作用和雌激素样作用有关,可为下一步实验验证提供理论基础。

Objective To explore the potential molecular mechanism of Dangguibuxue decoction(DGBXD) in the treatment of Osteoporosis(OP) based on the systemic network pharmacology.Methods The main chemical components,corresponding targets and target genes of DGBXD were screened by the Traditional Chinese Medicine System Pharmacology Technology PlatformTCMSP,and the known target genes related to OP were obtained by using GeneCards database.The target genes of DGBXD obtained were mapped to the OP disease targets to get the relevant predicted targets of DGBXD acting on OP.Cytoscape3.5.1 software was used to construct the effective active compound-disease targets network diagram,while used the STRING database to draw PPI network and used the R 3.6.3 software for key proteins analysis,target genes for GO function analysis and KEGG pathway enrichment analysis.Results The result indicated 17 active chemical constituents,7 key compounds,130 intersectional targets from drugs mapping to the OP disease as well as screening out 30 key targets;GO functional analysis revealed that the potential genes biological functions involved in the treatment of OP by DGBXD were mainly nuclear receptor activity,transcription factor activity,direct ligand,regulated sequence-specific DNA binding,steroid hormone receptor activity,cytokine receptor binding,cytokine activity,etc;The result of KEGG pathways enrichment analysis mechanism showed that the pathways were closely related to AGE-RAGE signaling pathways in diabetic complications,IL-17 signaling pathways,Hepatitis B,Prostate cancer,TNF signaling pathways,etc.Conclusion According to this study,DGBXD can treat on the OP through multi-component,multi-target and multi-pathway,which may be related to its anti-oxidation and estrogen-like effect,and it can further provide a theoretical basis for the next experimental verification.