Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90

Abstract

Objectives: In this study, we used network-based systems pharmacology analysis and molecular docking methods to predict the therapeutic mechanism of Scutellariae Radix on viral pneumonia.Methods: We screened active components of Scutellariae Radix and its’ genes by TCMSP. Also, we extracted viral pneumonia related target genes through Gene Cards, CTD and DisGeNet. To construct Protein-protein Interaction, STRING database was used. For functional enrichment, using SRplot platform, genes were classified by 3 categories: cellular component (CC), molecular function (MF) and biological process (BP). Molecular docking was conducted by AutoDockTools (version 4.2.6).Results: 32 Network-based systematic pharmacology analysis identified 37 target genes associated with baicalein. Based on the network and gene ontology analysis of the active ingredient's target genes and disease target genes, we identified nine core genes (<i>AKT1, BAX, BCL2, CASP3, HIF1A, PTGS2, RELA, TP53, VEGFA</i>) and HSP90 as involved. Notably, HIF1A showed the highest relevance, overlapping with two or more utilized programs. Hypoxia-inducible factor 1-alpha (HIF-1<i>α</i>) has been implicated in the expression of inflammatory cytokines, the induction of hypoxia, and the triggering of cytokine storms. Baicalein, a major component of SR, binds to both HIF-1 <i>α</i> and HSP90, suggesting that it may be a possible targeted treatment for viral pneumonia.Conclusions: Baicalein may bind to HIF-1<i>α</i> to control inflammation caused by viral infectious diseases and may also regulate hypoxic conditions to prevent impairment of lung function caused by an overactive immune system. These findings suggest further research into the molecular mechanisms involved in hypoxia and provide a scientific basis for improving the treatment of viral infectious diseases.