Utilizing integrating network pharmacological approaches to investigate the potential mechanism of Ma Xing Shi Gan Decoction in treating COVID-19

Beginning in December 2019, coronavirus disease 2019 (COVID-19), due to 2019-nCoV infection, emerged in Wuhan and spread rapidly throughout China and even worldwide. Employing combined therapy of modern medicine and traditional Chinese medicine has been proposed, in which Ma Xing Shi Gan Decoction (MXSGD) was recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. We investigated the underlying mechanism of MXSGD in treating COVID-19 utilizing the approaches of integrating network pharmacology. A total of 97 active ingredients of MXSGD were screened out, and 169 targets were predicted. The protein-protein interaction network exhibited hub targets of MXSGD, such as Heat shock protein 90, RAC-alpha serine/threonine-protein kinase, Transcription factor AP-1, Mitogen-activated protein kinase 1, Cellular tumor antigen p53, Vascular endothelial growth factor A, and Tumour necrosis factor. Gene Ontology functional enrichment analysis demonstrated that the biological processes altered within the body after taking MXSGD were closely related to the regulation of such processes as the acute inflammatory response, chemokine production, vascular permeability, response to oxygen radicals, oxidative stress-induced apoptosis, T cell differentiation involved in the immune response, immunoglobulin secretion, and extracellular matrix disassembly. KEGG enrichment analysis indicated that the targets of MXSGD were significantly enriched in inflammation-related pathways, immunomodulation-related pathways, and viral infection-related pathways. The therapeutic mechanisms of MXSGD on COVID-19 may primarily involve the following effects: reducing inflammation, suppressing cytokine storm, protecting the pulmonary alveolar-capillary barrier, alleviating pulmonary edema, regulating the immune response, and decreasing fever.