Network pharmacology-based study on the mechanisms of Guben Kangmin Formula for the treatment of chronic urticaria

[Objective] To predict the targets and signal pathways of Guben Kangmin Formula (GBKMF) in treating chronic urticaria (CU) based on network pharmacology and molecular docking methods, and to explore the mechanisms of its action. [Methods] The active ingredients in GBKMF were obtained from the databases of TCMSP, BATMAN-TCM, Berstein CNPD and literatures. The drug-like components were screened by “rule of five” after comparing with the computational chemical descriptors of small molecule drugs for CU. Principal component analysis (PCA) was further conducted, and potential active components and corresponding targets were obtained. Meanwhile, disease targets for CU were obtained from disease databases. The common targets of the potential active components of GBKMF and CU were explored and submitted to ClueGo and DAVID database for GO enrichment and KEGG pathway analyses. Afterwards, the common targets were submitted to STRING database to analyze the protein-protein interaction (PPI) for these targets. The results were imported into Cytoscape software for MCODE clustering and network topological property analyses to obtain the core targets. Then core targets were imported into BioGPS database to analyze the expression abundance of core targets in the skin, lymph nodes, CD4+ T cells and CD8+ T cells. At the same time, KEGG pathway enrichment analysis was performed for the core targets. [Results] A total of 1 124 ingredients in GBKMF and 25 small molecule drugs for CU were retrieved. Through drug-likeness property and principal component analyses, 349 potential active ingredients were screened, and 90 targets were predicted. The core targets such as HIF1A, IL6 and MAPK3 were obtained by MCODE clustering and topo logical property analyses. These core targets were expressed in the skin, lymph nodes, CD4+ T cells, and CD8+ T cells. GO analysis showed that these targets were associated with multiple biological processes, molecular composition, and cell function, such as inflammatory response, involving in the regulation of HIF-1 signaling pathway, TNF signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and other signaling pathways. Molecular docking results indicated that active ingredients, such as deoxyshikonin, yinyanghuoA, and 9-alpha hydroxyfragrinellone 9-o-beta-d-glucosid, regulated targets (INS, MAPK3, JAK2, etc.), accounting for the the therapeutic mechanism of GBKMF for psoriasis. [Conclusions] GBKMF has characteristics of being multi-component, multi-target, and multi-pathway in the treatment of chronic urticaria, and mechanisms of its action may be related to HIF-1 signaling pathway, TNF signaling pathway, Th17 cell differentiation, PI3K-Akt, and other signaling pathways.