Exploration on the Mechanism of Wenyang Yiqi Huoxue Prescription in the Treatment of Chronic Heart Failure Based on miR-126/PI3K/Akt Axis
10.19879/j.cnki.1005-5304.202505063
- VernacularTitle:基于miR-126/PI3K/Akt轴探讨温阳益气活血方治疗慢性心力衰竭作用机制
- Author:
Xianru ZHANG
1
;
Qingming QI
;
Yongfu QI
;
Ke DU
;
Xiaozhen MA
;
Chang LIU
Author Information
1. 青海省中医院,青海 西宁 810012
- Publication Type:Journal Article
- Keywords:
network pharmacology;
chronic heart failure;
miR-126-3p;
PI3K/Akt signaling pathway;
Wenyang Yiqi Huoxue Prescription
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(10):41-50
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of Wenyang Yiqi Huoxue Prescription(WYYQHXP)in the treatment of chronic heart failure(CHF)by regulating miR-126-3p and PI3K/Akt signaling pathway based on network pharmacology and experimental studies.Methods Active components and targets of WYYQHXP were obtained through TCMSP,SwissTargetPrediction,SwissADME and PubChem.Four miRNA databases were used to obtain miR-126-3p targets,and four disease databases were used to obtain CHF related targets.The intersection of the three was taken as the potential target of action;the protein-protein interaction network relationships of potential targets were explored using STRING and Cytoscape 3.9.1 software,and the main active components and core targets were screened;GO and KEGG pathway enrichment analysis was performed using R 4.2.1 software;Molecular docking was performed on the main active components with the core targets.Isoproterenol was used to induce a rat model of CHF with qi deficiency and blood stasis syndrome,and intervened with WYYQHXP.MiR-126-3p and core target expression in coronary endothelial cells were detected by immunohistochemistry,RT-qPCR,and Western blot.Results Network pharmacology screened main active components of WYYQHXP,including β-sitosterol,doustanol,kaempferol,quercetin,baicalein and luteolin,and the core targets of EGFR,VEGFA and AKT1;KEGG was enriched to the signaling pathways such as PI3K/Akt,and the 3 core targets were distributed to the PI3K/Akt signaling pathway;molecular docking showed good binding ability of β-sitosterol and stigmasterol to three core targets.Animal experiments showed that WYYQHXP could increase left ventricular ejection fraction and left ventricular fractional shortening in model rats(P<0.01),reduce serum brain natriuretic peptide content(P<0.01),increase expression of miR-126-3p(P<0.05,P<0.01,P<0.001),the medium-dosage of WYYQHXP could increase mRNA and protein expressions of EGFR,PI3K,AKT1 and VEGFA in coronary endothelial cells(P<0.01).Conclusion WYYQHXP may activate PI3K/Akt signaling pathway by acting on miR-126-3p,thereby restoring endothelial dependent vasodilation of coronary arteries,repairing endothelial dysfunction of coronary arteries,and treating CHF.