Elucidating the potential pharmaceutical mechanism of Gyejibokryeong-hwan on rosacea using network analysis

Abstract

Rosacea is a chronic erythematous disease with telangiectasia that affects the central area of the face. However, because of the ambiguity in the pathophysiology of rosacea, its treatment has not been clearly elucidated; therefore, new therapeutic options need to be developed. Gyejibokryeong-hwan (GBH) is widely used in clinical practice for various blood circulation disorders, including hot flushes. Therefore, we explored the potential pharmaceutical mechanism of GBH on rosacea and investigated the therapeutic points exclusive to GBH through comparative analysis with chemical drugs recommended in 4 guidelines for rosacea based on network analysis. The active compounds in GBH were identified, and the proteins targeted by these compounds and the genes related to rosacea were searched. Additionally, the proteins targeted by the guideline drugs were also searched to compare their effects. And the pathway/term analysis of common genes was conducted. Ten active compounds were obtained for rosacea. There were 14 rosacea-related genes targeted by GBH, with VEGFA, TNF, and IL-4, which were suggested as core genes. The pathway/term analysis of the 14 common genes revealed that GBH could potentially act on rosacea via 2 pathways: the "interleukin 17 signaling pathway" and the "neuroinflammatory response." Comparison and analysis of the protein targets between GBH and guideline drugs revealed that only GBH separately acts on the "vascular wound healing pathway." GBH has the potential to act on IL-17 signaling pathway, neuroinflammatory response and vascular wound healing pathway. Further studies are needed to determine the potential mechanism of GBH in rosacea.Abbreviations: DL = drug-likeness, GBH = Gyejibokryeong-hwan, GO = gene ontology, IL = interleukin, KEGG = Kyoto encyclopedia of genes and genomes, MMP = matrix metalloproteinase, NF = nuclear factor, NK = natural killer, OB = oral bioavailability, PPI = protein-protein interaction, TCMSP = traditional Chinese medicine systems pharmacology database and analysis platform, TNF = tumor necrosis factor, TRP = transient receptor potential, UV = ultraviolet, VEGFA = vascular endothelial growth factor A.