Exploring potential mechanisms of Suhexiang Pill against COVID-19 based on network pharmacology and molecular docking

Abstract

Background: The traditional Chinese medicine prescription Suhexiang Pill (SHXP), a classic prescription for the treatment of plague, has been recommended in the 2019 Guideline for coronavirus disease 2019 (COVID-19) diagnosis and treatment of a severe type of COVID-19. However, the bioactive compounds and underlying mechanisms of SHXP for COVID-19 prevention and treatment have not yet been elucidated. This study investigates the mechanisms of SHXP in the treatment of COVID-19 based on network pharmacology and molecular docking. Methods: First, the bioactive ingredients and corresponding target genes of the SHXP were screened from the traditional Chinese medicine systems pharmacology database and analysis platform database. Then, we compiled COVID-19 disease targets from the GeneCards gene database and literature search. Subsequently, we constructed the core compound-target network, the protein-protein interaction network of the intersection of compound targets and disease targets, the drug-core compound-hub gene-pathway network, module analysis, and hub gene search by the Cytoscape software. The Metascape database and R language software were applied to analyze gene ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock software was used for molecular docking of hub genes and core compounds. Results: A total of 326 compounds, 2450 target genes of SHXP, and 251 genes related to COVID-19 were collected, among which there were 6 hub genes of SHXP associated with the treatment of COVID-19, namely interleukin 6, interleukin 10, vascular endothelial growth factor A, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and epidermal growth factor. Functional enrichment analysis suggested that the effect of SHXP against COVID-19 is mediated by synergistic regulation of several biological signaling pathways, including Janus kinase/ STAT3, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), T cell receptor, TNF, Nuclear factor kappa-B, Toll-like receptor, interleukin 17, Chemokine, and hypoxia-inducible factor 1 signaling pathways. SHXP may play a vital role in the treatment of COVID-19 by suppressing the inflammatory storm, regulating immune function, and resisting viral invasion. Furthermore, the molecular docking results showed an excellent binding affinity between the core compounds and the hub genes. Conclusion: This study preliminarily predicted the potential therapeutic targets, signaling pathways, and molecular mechanisms of SHXP in the treatment of severe COVID-19, which include the moderate immune system, relieves the “cytokine storm,” and anti-viral entry into cells.

Application of network pharmacology in the study of the mechanism of action of traditional chinese medicine in the treatment of COVID-19

“…Network pharmacological analysis of Suhexiang Pill (SHXP) found that 326 compounds were screened out, such as quercetin and so on, among which 6 central genes were closely related to the treatment of diseases, including IL6, IL10, EGFR, TNF, etc. Through GO enrichment analysis, its therapeutic effects are mediated by synergistic regulation of multiple biological signaling pathways, including Interleukin 17, Toll-like receptor, Nuclear factor kappa-b, Janus kinase/STAT3and hypoxia-inducible factor 1 signaling Pathways SHXP works to treat severe COVID-19 by moderating cytokine storms inhibiting viral growth and regulating the body’s immune system ( Li, et al, 2021a ). Studies have proved that TNF signaling pathway is an important pathway of the inflammatory response, and its related factor receptors can play a role by inducing apoptosis, while quercetin, an important component, also plays an anti-inflammatory role by regulating TNF signaling pathway ( Berntsen, et al, 2018 ; Nishikawa, et al, 2018 ; Pang, et al, 2018 ).…”

Network pharmacology research of mechanism of Maxing Shigan Decoction in treating COVID‐19

“…In 1999, Shao Li firstly proposed the hypothesis that there is an interconnection between TCM and biomolecular networks. In September 2007, he constructed a research framework for TCM prescriptions based on biological networks [4]. Hopkins defined the concept of "network pharmacology" in October of the same year, the principle is to select specific nodes for multi-target drug design through network analysis of drug-target-disease, thereby improving the efficiency of drug development [5].…”