Exploration on Shengmai Decoction Targeting Bcl-2/Bax/Caspase-3 Pathway to Mediate Mitochondrial Apoptosis in Treatment of Heart Failure Based on Network Pharmacology
10.19879/j.cnki.1005-5304.202501148
- VernacularTitle:基于网络药理学探究生脉饮靶向Bcl-2/Bax/Caspase-3通路介导线粒体凋亡改善心力衰竭作用机制
- Author:
Xuan LIU
1
;
He FENG
;
Jingyang WANG
;
Yuting WANG
;
Rui ZHANG
;
Zilian ZHAN
;
Qiang XU
Author Information
1. 天津中医药大学研究生院,天津 301617
- Publication Type:Journal Article
- Keywords:
Shengmai Decoction;
heart failure;
network pharmacology;
mitochondria apoptosis;
Bcl-2/Bax/Caspase-3 pathway
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2025;32(9):22-30
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of Shengmai Decoction in improving heart failure by regulating mitochondrial apoptosis based on network pharmacology and experimental verification;To provide a basis for its clinical application.Methods The active components and targets of Shengmai Decoction were obtained through TCMSP and TCMID databases.Heart failure and mitochondrial apoptosis related targets were retrieved from GeneCards,OMIM,DrugBank,PharmGKB and TTD databases.A protein-protein interaction(PPI)network at the intersection of drugs and diseases was constructed using the STRING database,and a component-target network was constructed using Cytoscape 3.8.2 software.GO and KEGG pathway enrichment analysis was performed on intersecting targets using the DAVID database.Molecular docking was conducted to assess the binding affinity of key components to core target proteins.A rat model of heart failure was established,and the cardiac function of rats were detected by echocardiogram,ELISA was used to detect serum contents of BNP and NT-proBNP,mitochondrial ultrastructure was observed by transmission electron microscope,and Western blot was used to detect protein expressions of Bcl-2/Bax/Caspase-3 signaling pathway.Results A total of 66 active components and 146 targets of Shengmai Decoction were identified,and 22 intersecting targets with heart failure and mitochondrial apoptosis,including key proteins such as TNF,Bcl-2,Bax and Caspase-3.GO enrichment analysis revealed that the intersecting targets were closely associated with inflammation and cell signaling,while KEGG pathway analysis showed that the targets were primarily involved in the TNF signaling pathway,IL-17 signaling pathway,and mitochondrial function regulation.Molecular docking results indicated that Ginsenoside rh2,Beta-sitosterol and other components of Shengmai Decoction exhibited strong binding affinities with Bcl-2,Bax and Caspase-3.Animal experiments demonstrated that Shengmai Decoction significantly improved cardiac function(P<0.05,P<0.01),reduced serum BNP and NT-proBNP contents(P<0.01),alleviated mitochondrial damage,and inhibited mitochondrial apoptosis by upregulating Bcl-2 and downregulating Bax and Caspase-3 protein expression(P<0.01),thereby protecting cardiomyocytes.Conclusion Shengmai Decoction can target and regulate the Bcl-2/Bax/Caspase-3 signaling pathway,improving pathological processes associated with heart failure,which can provide a foundation for clinical optimization of Shengmai Decoction.
