Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanism of Qushi Huatan Decoction Against Coronary Heart Disease

Drug Des Devel Ther. 2024 Sep 11:18:4033-4049. doi: 10.2147/DDDT.S463054. eCollection 2024.

Abstract

Purpose: This study was designed to evaluate the effect and mechanism of the Qushi Huatan (QSHT) decoction against coronary heart disease (CHD) through network pharmacology and experimental verification.

Methods: In the present study, the active ingredients of the QSHT decoction were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS), then the potential ingredients and coronary heart disease targets were predicted using the SwissTarget Prediction database and the database of Genecards and OMIM database, respectively. A herb-compound-target network was constructed using Cytoscape. GO and KEGG enrichment analysis were performed using the ClusterProfiler data package of R software. Molecular docking was used to predict the core targets of QSHT against CHD. In addition, we used a myocardial infarction (MI) and high-fat diet ApoE-/- mice model to investigate the cardioprotective effects of QSHT. Western blotting and immunochemistry were used to verify the core targets and the signaling pathway.

Results: A total of 68 active ingredients were found in the QSHT decoction. Network pharmacology indicated 28 targets and 147 signal pathways, including AKT1, HIF-1α, GSK-3β, TLR4 and NF-κB, those key targets were also verified by molecular docking. The results of GO and KEGG enrichment analysis showed that the targets of QSHT against CHD were largely associated with inflammatory and oxidative stress, and AKT/HIF-1α and TLR4/NF-κB pathways might be key functional pathways. In vivo, QSHT significantly improved cardiac function and attenuated fibrosis and inflammation. Furthermore, QSHT could significantly inhibit the expression of HIF-1α, TLR4, phosphorylation of AKT1, GSK-3β and NF-κB after MI in ApoE-/- mice.

Conclusion: Based on network pharmacology, molecular docking and experimental verification, this study demonstrated that QSHT could improve cardiac function and attenuate cardiac fibrosis by regulating TLR4/NF-κB and AKT/HIF-1α signaling pathway in post- MI and high-fat diet ApoE-/- mice.

Keywords: Qushi Huatan decoction; coronary heart disease; molecular docking; network pharmacology.

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Coronary Disease* / drug therapy
  • Coronary Disease* / metabolism
  • Diet, High-Fat
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / chemistry
  • Drugs, Chinese Herbal* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Docking Simulation*
  • Network Pharmacology*
  • Signal Transduction / drug effects
  • Tandem Mass Spectrometry

Substances

  • Drugs, Chinese Herbal
  • Apolipoproteins E

Grants and funding

The present work was supported by Guangzhou Basic and Applied Basic Research Foundation (Grant Nos. 202201020348, 202201020488, and 2023A03J0742), National Natural Science Foundation of China (Grant No. 82074369), the Specific Fund of State Key Laboratory of Dampness Syndrome of Chinese Medicine (Grant Nos. SZ2021ZZ46, SZ2021ZZ12, SZ2021ZZ26, SZ2021ZZ33, SZ2023ZZ13 and SZ2022KF23), and the Traditional Chinese Medicine Bureau of Guangdong Province (Grant No. 20225019), Natural Science Foundation of Guangdong Province (Nos. 2022A1515010103, and 2023B1212060063).