摘要
Objective:This study aimed to explore the mechanism of Panax notoginseng(PNS)in the treatment of heart failure(HF)based on network pharmacology analysis combined with experimental verification.Materials and Methods:The potential targets and key pathways of effective components of PNS in the treatment of HF were revealed using network pharmacology.The postacute myocardial infarction(MI)HF rat model was established by ligating the left anterior descending branch of the coronary artery.The rats were divided into three groups:model,PNS,and fenofibrate groups.PNS(0.75 g/kg)and fenofibrate(10 mg/kg)were administered for 28 days.The efficacy and target mechanism of PNS in the treatment of HF were verified by cardiac ultrasound,Masson staining,and western blotting(WB)techniques.Results:The results of network pharmacology showed that seven potentially active compounds,such as quercetin,were obtained,involving 105 targets of HF;GO function was enriched to 1240 items;and KEGG enrichment covered 1240 signal pathways.The results of echocardiography showed that EF and FS of HF rats after MI were significantly increased,while Left ventricular internal dimension diastole(LVIDd)and Left ventricular internal dimension systole(LVIDs)were significantly decreased(P<0.001,P<0.05).Masson staining showed that PNS could reduce the degree of myocardial fibrosis(MF)in HF.The results of WB showed that PNS could reduce the expression of the p-p38-MAPK,transforming growth factor-beta(TGF-β),and Smad3 in HF rats.Conclusion:PNS inhibited MF and treated HF by regulating p-p38 MAPK-TGF-βpathway,which lays a theoretical foundation for further study of its pharmacological mechanism and key target.
基金
supported by the National Natural Science Foundation of China(grant number 81822049)
the Major New Drug Creation of the Ministry of Science and Technology(grant number 2019ZX09201004-001-011)。