淫羊藿治疗糖皮质激素性骨质疏松症分子机制的网络药理学分析

目的利用网络药理学方法探索淫羊藿治疗糖皮质激素性骨质疏松症(glucocorticoid-induced osteoporosis,GIOP)的分子作用机制。方法运用中药系统药理学数据库与分析平台(TCMSP)筛选淫羊藿的活性成分及相关靶点;运用Gene Cards数据库、OMIM数据库获取GIOP的疾病靶点;通过R语言将药物靶点与GIOP疾病靶点取交集;利用Cytoscape 3.7.0软件构建"淫羊藿-活性成分-GIOP靶点"网络;运用String数据库构建"淫羊藿-GIOP"共同靶点蛋白互作网络;运用R语言进行GO生物功能和KEGG通路富集分析。结果通过筛选获得淫羊藿的23个主要活性成分,一共涉及GIOP相关的65个靶点;槲皮素(quercetin)、山奈酚(kaempferol)、木犀草素(luteolin)和淫羊藿苷(anhydroicaritin)能与10个以上相关靶点连接,是淫羊藿治疗GIOP的主要成分;白细胞介素-6(IL-6)、血管内皮生长因子A(VEGFA)、丝裂原激活蛋白激酶-8(MAPK8)、胱冬酶-3(CASP3)和雌激素受体-1(ESR1)是"淫羊藿-GIOP"共同靶点蛋白互作关系中连接次数最多的5个靶点,为核心靶点基因。结论淫羊藿有可能是通过前列腺癌信号通路、细胞凋亡信号通路、流体剪切应力与动脉粥样硬化信号通路、TNF信号通路和糖尿病并发症中AGE-RAGE信号通路等多个途径发挥治疗GIOP的作用。为后期的药效机制研究提供了新的思路和方向。

Network pharmacology analysis of the molecular mechanism of herba epimedii in the treatment of glucocorticoid-induced osteoporosis

Objective To explore the molecular mechanism of herba epimedii in the treatment of glucocorticoid-induced osteoporosis (GIOP) with network pharmacology. Methods The active ingredients and related targets of herba epimedii were screened with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The disease target of GIOP was obtained with Used GeneCards database and OMIM database. The drug target was intersected with the GIOP disease target through R language. The Cytoscape 3.7.0 software was used to construct a network of herba epimedii-active ingredient-GIOP target. Herba epimedii-GIOP protein-protein interaction (PPI) network was constructed using the String database. The gene ontology (GO) biological function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway were analyzed using R language. Results Twenty-three major active ingredient of herba epimedii were obtained through the screening, and a total of 65 GIOP-related targets were involved. Quercetin, kaempferol, luteolin, and icariin connected with more than 10 related targets, which were the main components of epimedium in the treatment of GIOP. IL-6, VEGFA, MAPK8, CASP3, and ESR1 were the five most frequently linked targets in the interaction of common target protein of epimedium-GIOP, which were the core target genes. Conclusion Herba epimedii may have the treatment effect on GIOP through prostate cancer pathway, cell apoptosis pathway, fluid sheer stress and atherosclerosis pathway, TNF signal pathway, and AGE-RAGE signal pathway in diabetes. This provides a new thought and direction for the study of the mechanism of pharmacodynamics.