Study on mechanism of the Hanshi Zufei syndrome formula for COVID-19 based on network pharmacology

Abstract Objective To study the mechanisms of Hanshi Zufei syndrome formula (HSZF) for coronavirus disease 2019 (COVID-19) using network pharmacology. Methods We screened the potential active constituents (oral bioavailability [OB] ≥ 30%, drug-likeness [DL] ≥ 0.18) of HSZF using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, predicted targets using the Swiss TargetPrediction database, constructed a pharmacologically active-compound–potential-target network and a protein–protein interaction (PPI) network using Cytoscape software, and used the org.Hs.eg.db and ClusterProfiler data packages in R language software to perform gene ontology (GO) biological-function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the potential targets of HSZF. Results A total of 170 effective active constituents, such as Genkwanin, diosmetin, wogonin, quercetin, kaempferol, luteolin, and herbacetin were obtained through oral OB and DL screenings. These constituents act on targets such as kininogen-1 (KNG1), epidermal growth factor receptor (EGFR), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), EStrogen Receptor 1 (ESR1), angiotensin-converting enzyme 2 (ACE2), and myeloperoxidase (MPO); participate in biological processes such as cellular metal ion homeostasis, calcium ion homeostasis, unsaturated fatty acid metabolism, and positive regulation of phospholipase activity; and treat COVID-19 through pathways such as apoptosis, calcium signaling, phospholipase D signaling, arachidonic acid metabolism, platelet activation, renin–angiotensin system (RAS), and inflammatory-mediator regulation of transient receptor potential (TRP) channels. Conclusion Flavonoids are important in the mechanism by which HSZF treats COVID-19. Inhibition of inflammatory response and regulation of both immune function and cell apoptosis might be important mechanisms of HSZF for this disease.