基于网络药理学的黄芪抗肺纤维化机制预测与验证研究

目的 通过网络药理学分析和实验验证阐释黄芪抗肺纤维化作用机制.方法 从中药系统药理学数据库和分析平台、中药分子机制的生物信息学分析工具中获取黄芪所有化学成分和对应靶点,从DrugBank和DisGeNET数据库获取肺纤维化疾病相关靶点,两者取交集,获得黄芪治疗肺纤维化潜在作用靶点,采用Cytoscape构建成分-靶点图...

Mechanism prediction and validation research of Huangqi (Astragali Radix) in the treatment of pulmonary fibrosis based on network pharmacology

Objective To explore the potential mechanism of Huangqi(Astragali Radix) in the treatment of pulmonary fibrosis based on network pharmacology and experimental verification. Methods All chemical components and corresponding targets of Huangqi(Astragali Radix) were obtained from traditional Chinese medicine systems pharmacology database and analysis platform and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, and pulmonary fibrosis disease related targets were obtained from DrugBank and DisGeNET databases. The intersection of the two was taken to obtain the potential targets of Huangqi(Astragali Radix) in the treatment of pulmonary fibrosis. The component-target map was constructed by Cytoscape. After topological analysis, the key active components of Huangqi(Astragali Radix) in the treatment of pulmonary fibrosis were screened by Degree value. The target protein interaction map was constructed by STRING to screen the core targets. The pathways involved in the treatment of pulmonary fibrosis by Huangqi(Astragali Radix) were obtained by Enrichr analysis. The effects of Huangqi(Astragali Radix) extract on the expression of TGF-β, PTGS2 and P-ErK1/2 proteins in bleomycin-induced rat alveolar macrophages was observed. Results Huangqi(Astragali Radix) contained 76 chemical components that acted on 563 targets, 932 targets related to pulmonary fibrosis disease and 97 targets of intersection. The top 4 components in the map of Huangqi(Astragali Radix)components-targets of pulmonary fibrosis disease network were quercetin, kaempferol, daidzein, canavanine. The suppositional targets were PTGS2, MAPK1, MAPK14, EGF, JUN, involving AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, cancer, IL-17 signaling pathway and so on. Low, medium and high doses of Huangqi(Astragali Radix) extract could down-regulate the content of TGF-β1 and PTGS2 in bleomycin-induced NR8383 cells(P<0.05), and down-regulate the expression of P-ERK1/2(P<0.05, P<0.01). Conclusion Huangqi(Astragali Radix) can act on the whole course of pulmonary fibrosis through multicomponent, multi-target and multi-action pathway, the mechanism may be related to down-regulating the expression of TGF-β,PTGS2 and p-ERK1/2 in pulmonary macrophage, which provides a basis for studying on the mechanism of Huangqi(Astragali Radix) in treating pulmonary fibrosis.