Study on the Effect and Mechanism of Danbie Capsule in Treating Uterine Fibroid Based on Network Pharmacology and Cell Experiments
Objective To explore the effect and mechanism of Danbie Capsule in treating uterine fibroid (UF)based on network pharmacology and cell experiments. Methods Databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),Traditional Chinese Medicines Integrated Database (TCMID),GeneCards,and DisGeNET were used to search for anti-UF targets of Danbie Capsule. Protein-protein interaction network (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment were used to screen key targets and key pathways. The optimal ingredients and targets of Danbie Capsule against UF were determined through the "key ingredients-key targets-key pathways" network,and the affinity between the target and the ingredient was verified by molecular docking. Human primary uterine fibroid cells were used for invasion,migration and apoptosis experiments,and Western Blot technology was used to verify the key protein pathways,which were predicted by network pharmacology. Results It was found that 144 active ingredients of Danbie Capsule,which act on 111 potential targets of UF. A total of 30 key targets including AKT1,IL6,TP53,VEGFA and TNF were involved in regulating 20 key signaling pathways such as cancer pathway,IL-17 signaling pathway and PI3K/AKT pathway. The key ingredient(quercetin)has a good affinity with the key target(AKT1). The experimental results of the cells showed that Danbie Capsule can significantly reduce the invasion ability and migration rate of uterine fibroid cells,promote apoptosis of uterine fibroid cells,increase Bax protein expression,and reduce the protein expression of Bcl-2,p-PI3K and p-AKT (P<0.01,P<0.001,P<0.0001). Conclusion Danbie Capsule can treat UF through multiple components,multiple targets and multiple pathways. Quercetin and AKT1 are the main active components and core targets. The effects of pro-apoptosis,anti-invasion and anti-migration are closely related to regulating the expression of Bcl-2 and Bax,and down-regulating the PI3K/AKT pathway.
万方数据
维普
