活血化瘀中药治疗股骨头坏死共同作用机制的网络药理学数据

Common mechanism of Chinese herbs for promoting blood circulation and removing blood stasis in the treatment of osteonecrosis of the femoral head:an analysis based on network pharmacology

背景:有文献报道了活血化瘀类中药是治疗股骨头坏死的最常用中药,而川芎、牛膝、丹参、骨碎补、红花为治疗股骨头坏死最常用的活血化瘀中药。目的:探讨五味(川芎、牛膝、丹参、骨碎补、红花)临床常用的活血化瘀中药治疗股骨头坏死的共同作用机制。方法:通过中药系统药理学分析平台数据库(TCMSP)搜索,获得五味中药的主要活性成分,并推测其作用基因靶点,再通过Excel表格取交集函数获得五味中药共同能作用的潜在基因靶点。通过GeneCards和OMIM数据库获得股骨头坏死疾病的相关靶点。构建活血化瘀中药-治疗成分-靶点-股骨头坏死网络图,进行基因本体论(GO)功能和KEGG通路富集分析。结果与结论:①通过TCMSP数据库搜索共筛选出五味中药有效活性成分132种,相应得到2593个潜在作用靶点基因,五味中药共有的潜在作用靶点有31个;通过搜索OMIM、GeneCards数据库得705个与股骨头坏死疾病相关靶点,取交集后得到五味活血化瘀中药共有-股骨头坏死疾病交集基因8个(PPARG、NOS3、F2、NCOA2、NOS2、GSK3B、ESR1、NR3C1);②GO生物分析显示活血化瘀中药治疗股骨头坏死的主要生物过程与血小板活化负调控、一氧化氮生物合成过程、血管舒张的正调控等有关;③KEGG通路显示活血化瘀中药治疗股骨头坏死的主要通路与甲状腺激素信号通路、缺氧诱导因子1信号通路、催乳激素信号通路、雌激素信号通路等密切相关;④推测活血化瘀类中药治疗股骨头坏死的可能主要机制可能是:活血化瘀中药中的有效成分槲皮素、小檗碱、黄连碱、丹参新酮等通过作用于ESR1、NOS3、NOS2、PPARG等靶点,从而参与调控甲状腺激素信号通路、缺氧诱导因子1信号通路、催乳素信号通路、雌激素信号通路等,通过调控成骨与破骨细胞活性,改善血液高凝状态及血管通透性、促进血管的新生,进一步促进坏死的股骨头进行修复而达到治疗作用。该研究只是对作用机制的预测探讨,具体的作用机制还需后续的实验进行验证。

BACKGROUND:Chinese herbs for promoting blood circulation and removing blood stasis are the most commonly used Chinese medicines for the treatment of osteonecrosis of the femoral head(ONFH),while Chuanxiong,Achyranthes bidentata,Salvia miltiorrhiza,rhizoma drynariae,and safflower are the most commonly used herbs for treating ONFH.OBJECTIVE:To explore the common mechanism of five Chinese herbs for promoting blood circulation and removing blood stasis in the treatment of ONFH METHODS:The main active ingredients of five herbs were obtained by searching the database of TCM system pharmacology analysis platform(TCMSP),and the gene targets of five herbs were speculated.Then the potential gene targets of all five traditional Chinese herbs could be obtained by taking the intersection function through the Excel table.Relevant targets of ONFH disease were obtained through GeneCards and OMIM databases.Chinese herbs for promoting blood circulation and removing blood stasis-therapeutic ingredients-targets-ONFH network was constructed,followed by gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.RESULTS AND CONCLUSION:A total of 132 active ingredients of five herbs were screened out through the TCMSP database search,with 2593 potential target genes correspondingly.There were 31 common potential targets of these five herbs.A search of OMIM and GeneCards databases yielded 705 ONFH diseaserelated targets,and 8 intersected genes(PPARG,NOS3,F2,NCOA2,NOS2,GSK3B,ESR1,NR3C1)were obtained.GO biological analysis showed that the main biological process of five Chinese herbs in ONFH was related to negative regulation of platelet activation,nitric oxide biosynthesis,and positive regulation of vasodilation.The KEGG pathway analysis showed that the main pathway of five Chinese herbs in ONFH was related to Thyroid hormone signaling pathway,hypoxia-inducible factor-1 signaling pathway,prolactin signaling pathway,and estrogen signaling pathway.The possible main mechanisms of five Chinese herbs in the treatment of ONFH may be:the effective ingredients in herbs such as quercetin,berberine,coptisine,miltirone,by acting on ESR1,NOS3,NOS2,PPARG and other targets,participate in the regulation of thyroid hormone signaling pathway,hypoxia-inducible factor-1 signaling pathway,prolactin signaling pathway,and estrogen signaling pathway,and by regulating the activity of osteoblast and osteoclast,they can improve the hypercoagulability of blood and vascular permeability and promote angiogenesis,further promoting the repair of the necrotic femoral head to achieve the therapeutic effect.However,this study only predicted the mechanism of action,and the specific mechanism of action still needs to be verified by follow-up experiments.