基于网络药理学和细胞生物学研究黄芪治疗糖尿病肾病的作用机制

目的 运用网络药理学和细胞生物学验证探讨黄芪治疗糖尿病肾病的分子作用机制.方法 通过中药系统药理学数据库(TCMSP)筛选出黄芪有效成分;利用Drugbank数据库、GeneCards和OMIM数据库筛选黄芪有效成分和糖尿病肾病的相关靶点;应用String数据库绘制PPI网络;通过Cytoscape软件绘制黄芪-成分-...

Exploration into the Mechanism of Effective Components and Potential Targets of Astragali Radix in Treatment of Diabetic Nephropathy Based on Network Pharmacology and Cell Biology Verification

OBJECTIVE To explore the molecular mechanism of Astragali Radix in the treatment of diabetic nephropathy(DN) by the network pharmacology and cell biology verification. METHODS The main active ingredients of Astragali Radix were obtained through TCMSP. Drugbank, Gene Cards and OMIM were used to predict and screen the targets of Astragali Radix and DN. The PPI network was constructed using the String database. The GO and KEGG pathways involved in the targets were analyzed by DAVID. The ingredients-targets-diseases network was constructed by Cytoscape software. Cell biology verification analyzes the protective effect of active ingredients in Astragali Radix on DN. RESULTS The results showed that 12 active components and 56 targets of Astragali Radix were involved. The network results showed that the process of oxidative stress, inflammation, apoptosis were mainly involved, which played a role in the treatment of DN by adjusting the MAPK, HIF, ErbB, p53, NF-κB and other signal pathways. Its mechanism of action involved antioxidation, anti-inflammatory and anti-apoptosis. Cell biology verification analysis showed that quercetin and kaempferol could reduce cell apoptosis caused by high glucose, reduce ROS level(P<0.05), and improve CAT and SOD capacity(P<0.05). Quercetin could significantly reduce the protein expression levels of phosphorylated P38 MAPK and JNK in HK-2 cells caused by high glucose(P<0.01). CONCLUSION In the current study, the mechanism of Astragali Radix in the treatment of DN by network pharmacology was explored. Results showed that Astragali Radix could act on multi-ingredient, multi-target and multi-pathway played a potential therapeutic role on DN. The prediction results of network pharmacology suggest that the quercetin and kaempferol in Astragali Radix might be the material basis for treatment of DN. The analysis proved the quercetin and kaempferol in Astragali Radix can reduce cell damage caused by high glucose, reduce oxidative stress, and improve antioxidant capacity by in vitro experiment, providing a new idea for Astragali Radix in the treatment of DN.