祛痰逐瘀治疗股骨头坏死的网络药理学分析

Mechanism of Qutan Zhuyu Decoction for osteonecrosis of the femoral head based on network pharmacology

背景:中医认为早期的骨蚀病多为痰瘀互结型,故早期治疗股骨头坏死多采用痰瘀同治法。网络药理学可构建药物的“成分-靶标-通路-疾病”网络,深入探究药物与疾病的关系,从而多层次地阐明药物的作用机制。目的:构建祛痰逐瘀方活性成分-股骨头坏死-靶点网络,探讨祛痰逐瘀方治疗股骨头坏死的关键靶点和作用机制。方法:桃红四物汤合二陈汤是治疗早期股骨头坏死的有效方剂,截取其中代表药物:半夏、陈皮、茯苓、桃仁和红花,命名为祛痰逐瘀方。在中药计算系统药理学分析平台(TCMSP)检索并筛选祛痰逐瘀方的主要有效成分和作用靶点;通过人类基因数据库和人类孟德尔遗传数据库(OMIM)检索股骨头坏死的相关疾病靶点;制作韦恩图获取祛痰逐瘀方与股骨头坏死的共同靶点,利用Cytoscape软件构建中药-成分-疾病-靶点调控网络,然后通过STRING数据平台建立PPI网络,最后利用Bioconductor平台和R语言进行基因本体(GO)富集分析和基因相互作用(KEGG)通路分析。结果与结论:①祛痰逐瘀方中发挥治疗股骨头坏死的成分主要是sitosterol、naringenin等78个活性成分,发挥治疗作用的靶点可能包括NCOA2、PTGS1等61个关键靶点;②影响治疗股骨头坏死生物学过程主要为近端启动子序列特异性DNA结合、DNA结合转录活性调控等,发挥治疗的关键作用通路包括白细胞介素17信号通路、细胞凋亡等;③祛痰逐瘀方对股骨头坏死的治疗作用体现了中药多成分-多靶点-多通路的特点,提示其作用机制可能是通过多成分、多靶点、多通路实现。

BACKGROUND:Traditional Chinese medicine believes that the early bone erosions mostly belong to phlegm and blood stasis,so early treatment of osteonecrosis of the femoral head(ONFH)is often similar to the treatment of phlegm and blood stasis.Based on network pharmacology we can build a“component-targetpathway-disease”network of drugs to explore the relationship between drugs and diseases,thereby clarifying the mechanism of drugs OBJECTIVE:To construct the component-target-pathway-disease network of Qutan Zhuyu Decoction and to explore the key targets and mechanism of Qutan Zhuyu Decoction in the treatment of ONFH.METHODS:Taohong Siwu Decoction and Erchen Decoction are effective prescriptions for the treatment of early ONFH.The representative drugs include Pinellia tangerine peel,medlar,peach kernel and safflower,named as Qutan Zhuyu Decoction.The main active components and targets of Qutan Zhuyu Decoction was searched and screened in the Chinese Medicine Computing System Pharmacology Analysis Platform(TCMSP),and a search for ONFH targets in the Human Gene Database(GeneCards)and the Human Mendelian Genetic Database(OMIM)was performed.The common targets of Qutan Zhuyu Decoction and ONFH were got by Venn diagrams.Cytoscape3.6.1 was used to construct a Chinese medicine-ingredient-disease-target regulation network,then establish a protein-protein interaction network through the STRING data platform,and finally use the Bioconductor platform and R language for gene ontology enrichment analysis and gene interaction(KEGG)pathway analysis.RESULTS AND CONCLUSION:The main components of Qutan Zhuyu Decoction for the treatment of ONFH were 78 active components such as sitosterol and naringenin.The targets for therapeutic effects might include 61 key targets such as NCOA2 and PTGS1.The biological processes affecting the treatment of ONFH mainly included proximal promoters,sequence-specific DNA binding,and regulation of DNA-binding transcriptional activity.Key pathways for therapeutic use included interleukin-17 signaling pathway and apoptosis.Overall,the therapeutic effect of Qutan Zhuyu Decoction on ONFH reflects the characteristics of multi-component-multi-target-multi-channel of traditional Chinese medicine,suggesting that its mechanism may be achieved by multi-components,multi-targets and multi-channels.