摘要
目的基于网络药理学及细胞实验探讨丹鳖胶囊抗子宫肌瘤的作用及机制。方法检索中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)、GeneCards、DisGeNET等,挖掘丹鳖胶囊抗子宫肌瘤靶点;利用蛋白互作网络(PPI)及基因组百科全书(KEGG)信号通路富集筛选关键靶点及通路;通过关键成分-关键靶点-关键通路网络确定丹鳖胶囊抗子宫肌瘤最佳成分、最佳靶点,以分子对接验证两者的亲和力。采用原代人子宫肌瘤细胞进行侵袭、迁移及凋亡实验,应用Western Blot技术验证网络药理学预测的关键蛋白通路。结果丹鳖胶囊的144个活性成分作用于111个子宫肌瘤潜在靶点;AKT1、IL6、TP53、VEGFA、TNF等30个关键靶点参与调控癌症通路、IL-17信号通路、PI3K/AKT通路等20条关键信号通路;最佳成分槲皮素与最佳靶点AKT1有良好的亲和力。细胞实验显示丹鳖胶囊能显著降低子宫肌瘤细胞的侵袭力及迁移率,促进子宫肌瘤细胞凋亡,提高蛋白Bax表达,降低蛋白Bcl-2、p-PI3K、p-AKT的表达(P<0.01,P<0.001,P<0.0001)。结论丹鳖胶囊能多成分、多靶点、多通路抗子宫肌瘤,槲皮素与AKT1是其最佳成分及靶点,其促凋亡、抗侵袭、抗迁移作用与调控Bcl-2、Bax表达,下调PI3K/AKT通路密切相关。
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.
作者
李杭林
温小丽
武亭宇
王博龙
LI Hanglin;WEN Xiaoli;WU Tingyu;WANG Bolong(The People’s Hospital of Santai County,Mianyang 621100 Sichuan,China;The Second People’s Hospital of Yichun City,Yichun 336000 Jiangxi,China;The People’s Hospital of Jiexiu City,Jiexiu 032000 Shanxi,China;Yichun University,Yichun 336000 Jiangxi,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2024年第12期1868-1875,共8页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
四川省医院协会2022年度青年药师科研专项资金项目(22039)
江西省教育厅科技项目(GJJ211617)。
