Aiyuan Cai¹, Siting Xu¹, Jie He², Meiping Shi¹, Lanlin You¹, Zhongbin Pan¹, Yanxia Zheng³

Abstract

Purpose: To investigate the primary components and effect of Danshen-Chuanxiong (DS-CX) in the treatment of Kawasaki disease. Methods: Active ingredients of DS-CX and targets of action were screened via the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) and SwissTargetPrediction databases. Targets of Kawasaki disease were queried in OMIM, GeneCards, DRUGBANK, and Disgenet databases, and intersected with drug targets. Protein-protein interaction maps (PPIs) were constructed using STRING database and Cytoscape software, and core genes of Kawasaki disease were screened. Pathway enrichment analyses (DAVID database, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG)) were conducted for DS-CX targeting Kawasaki disease crossover targets. Results: A total of 64 active ingredients and corresponding potential target genes of DS-CX were obtained. Also, 928 human genes related to Kawasaki disease were obtained from OMIM, DRUGBANK, GeneCards and Disgenet databases. Potential target genes of DS-CX was intersected with 928 human Kawasaki disease-related genes, and a total of 55 genes were screened. The PPI network was built using STRING database and Cyotoscape software, and overlapping genes were further screened. A total of 61 active ingredients were screened for their effects on Kawasaki disease-related targets. GOfunction analysis revealed that DS-CX affected Kawasaki disease by positively regulating gene expression. Also, KEGG enrichment analysis found that DS-CX and Kawasaki disease was mainly enriched in pathways involved in cancer. Conclusion: DS-CX regulates core genes (AKT1, IL6, and TP53) and other genes through active ingredients which in turn act on cancer pathway. Thus, DS-CX demonstrates anti-inflammatory and anti-platelet activities and helps blood vessel repair and remodeling in Kawasaki disease. Further studies to validate Danshen and Chuanxiong for the treatment of Kawasaki disease are needed to determine its mechanism of action