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Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology
Yan-Gu Tao1,2, Xiu-Fang Huang1, Jun-Yan Wang1
1The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Insights
Huangqi shows potential for treating heart failure (HF) by impacting multiple targets and pathways, including AGE-RAGE signaling. Network pharmacology identified key compounds and molecular mechanisms for this cardiovascular disease treatment.
Area of Science:
- Herbal medicine research
- Systems pharmacology
- Cardiovascular disease mechanisms
Background:
- Heart failure (HF) is an advanced stage of cardiovascular diseases with high incidence.
- Huangqi is recognized for its multitarget, multipathway efficacy in cardiovascular disease treatment.
Purpose of the Study:
- To elucidate the molecular mechanisms of Huangqi in treating heart failure (HF) using network pharmacology.
- To identify key compounds and molecular targets of Huangqi relevant to HF treatment.
Main Methods:
- Network pharmacology approach utilizing TCMSP, PubChem, Cytoscape, STRING, and Metascape databases.
- Construction of compound-target and protein-protein interaction networks.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Molecular docking simulations to assess compound-target binding affinity.
Main Results:
- Identified 407 targets for 21 Huangqi compounds and 378 targets for HF.
- Discovered 46 overlapping targets, enriched in pathways like AGE-RAGE signaling, IL-17, and HIF-1 signaling.
- Top Huangqi compounds demonstrated favorable binding activities with key targets compared to digoxin.
Conclusions:
- Huangqi exhibits potential as a multitarget, multipathway therapeutic agent for heart failure (HF).
- The study highlights Huangqi's ability to modulate critical signaling pathways involved in HF pathogenesis.
- Further investigation into Huangqi's molecular mechanisms could lead to novel HF treatment strategies.
Abstract:
Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.
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