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Decoding the Mechanism of Shixiao Powder in Treating Coronary Heart Disease Based on Network Pharmacology and Molecular Docking

ABSTRACT: Shixiao powder comes from the Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and consists of two herbs, Puhuang (PH) and Wulingzhi (WLZ). PH-WLZ is a commonly used drug pair for the treatment of coronary heart disease (CHD), and its clinical effect is remarkable. However, our understanding of the mechanism of treatment of CHD is still unclear. In this study, the method of network pharmacology was used to explore the mechanism of PH-WLZ in the treatment of CHD. A total of 56 active ingredients were identified from PH-WLZ, of which 93 targets of 41 active ingredients overlapped with those of CHD. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with CHD and those associated with the mechanism of PH-WLZ in the treatment of CHD. By constructing the protein-protein interaction (PPI) network of common targets, 10 hub genes were identified. Based on the number of hub genes contained in the enrichment analysis, we obtained the key pathways of PH-WLZ in the treatment of CHD. The key KEGG pathway in the treatment of CHD by PH-WLZ is mainly enriched in atherosclerosis, inflammation, immunity, oxidative stress, and infection-related pathways. Moreover, the results of molecular docking showed that the active ingredients of PH-WLZ had a good affinity with the hub genes. The results indicate that the mechanism of PH-WLZ in the treatment of CHD may be related to regulation of lipid metabolism, regulation of immune and inflammatory responses, regulation of downstream genes of fluid shear stress, antiaging and oxidative stress, and virus inhibition.

SUBMITTER: Jiang Z

PROVIDER: S-EPMC9279019 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Hawthorn leaves, which is a traditional Chinese medicine (TCM), has been used for treating coronary heart disease (CHD) for a long time in China. But the limited understanding of the main active components and molecular mechanisms of this traditional medicine has restricted its application and further research. The active compounds of hawthorn leaves were obtained from TCMSP database and SymMap database. The targets of it were predicted based on TCMSP, PubChem, Swiss Target Prediction, and SymMap database. The putative targets of CHD were gathered from multi-sources databases including the Online Mendelian Inheritance in Man (OMIM) database, the DrugBank database, the GeneCards database and the DisGeNet database. Network topology analysis, GO and KEGG pathway enrichment analyses were performed to select the key targets and pathways. Molecular docking was performed to demonstrate the binding capacity of the key compounds to the predicted targets. Furthermore, RAW264.7 cells stimulated by lipopolysaccharides (LPS) were treated with three effective compounds of hawthorn leaves to assess reliability of prediction. Quercetin, isorhamnetin and kaempferol were main active compounds in hawthorn leaves. Forty four candidate therapeutic targets were identified to be involved in protection of hawthorn leaves against CHD. Additionally, the effective compounds of it had good binding affinities to PTGS2, EGFR, and MMP2. Enrichment analyses suggested that immune inflammation related biological processes and pathways were possibly the potential mechanism. Besides, we found that three predicted effective compounds of hawthorn leaves decreased protein expression of PTGS2, MMP2, MMP9, IL6, IL1B, TNFα and inhibited activation of macrophage. In summary, the present study demonstrates that quercetin, kaempferol and isorhamnetin are proved to be the main effective compounds of hawthorn leaves in treatment of CHD, possibly by suppressing expression of PTGS2, MMP2, MMP9, inflammatory cytokines and macrophages viability. This study provides a new understanding of the active components and mechanisms of hawthorn leaves treating CHD from the perspective of network pharmacology.

Project description:BackgroundCoronary heart disease (CHD) is one of the most important complications of diabetes mellitus, having a high disability fatality rate. Qiweitangping is a Chinese medicine to control diabetes (type 1 and type 2 diabetes) and complications, having been used in clinic for more than 20 years, with the expected therapeutic effect. In a previous clinical study, the total effective rate of the drug for the treatment of type 2 diabetes reached 92.7%. However, the mechanism of the treatment process is unclear. Therefore, this research was conducted to explore the mechanism of treating diabetic coronary heart disease with the assistance of bioinformatics methods.MethodsThe TCMSP database was used to collect the effective chemical constituents of Qiweitangping and the target genes of the chemical constituents, and the related genes of diabetic CHD were obtained from the GeneCard database. Furthermore, the intersection was found between the target gene of the drug and the related gene of the disease to obtain the candidate genes; the STRING database and DAVID database were used to perform protein interaction analysis and KEGG enrichment analysis on the candidate genes. Also, molecular docking was used for auxiliary verification. Finally, a "drug component-gene target-pathway" network was constructed by using Cytoscape software.ResultsSixty-two effective chemical components including naringin, diosgenin, formogenin, isorolin, and isocryptanshinone, fifty-nine candidate target genes (such as AKT1, CASP3, and VEGF-A), and thirty-nine related pathways in Qiweitangping were obtained. In addition, two pairs (CASP-naringenin and STAT3-cryptotanshinone) of molecular docking results showed good affinity (<-5.00 kcal/mol).ConclusionThe results of the study indicate that Qiweitangping treats diabetic CHD with multiple chemical components. Its mechanism of action may be related to the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and ErbB signaling pathway. STAT3 and CASP genes have been verified by molecular docking to have a relatively good combination with Qiweitangping. This study is the theoretical basis for further experimental study on the treatment mechanism of diabetic CHD with Qiweitangping.

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Decoding the Mechanism of Shixiao Powder in Treating Coronary Heart Disease Based on Network Pharmacology and Molecular Docking

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