Network Pharmacology Systematically Uncovers Multiple Mechanisms of Zhisousan (止嗽散) for Treatment of Chronic Cough

Abstract

IntroductionZhisousan is a classical prescription consisting of seven Chinese herbal medicines and has been used historically in the treatment of chronic cough. The aim of this study was to identify the chemical constituents and targets of Zhisousan using network pharmacological analysis. MethodsParameters such as the oral utilization rate and the drug similarity of ingredients in Zhisousan were obtained. The effective ingredients of traditional Chinese medicine were screened, and targets of effective ingredients of traditional Chinese medicine were collected by the TCMSP database. Genes related to chronic cough were collected by the GeneCards database, and key targets were obtained after intersecting with the targets of Zhisousan. The above targets were analysed using the String database, and a protein-protein interaction network (PPI network) was constructed. Finally, GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out on key targets. ResultsAfter iteratively screening and removal of duplicates, 151 active ingredients and 2022 targets of Zhisousan were obtained. There were 2348 genes related to the chronic cough disease and 79 targets for drug and disease identified. PPI network analysis suggested that IL6 (Interleukin-6), VEGFA (Vascular endothelial growth factor A), EGFR (Epidermal growth factor receptor) and CASP3 (Caspase-3) may be the key targets of Zhisousan in the treatment of chronic cough. ConclusionNetwork pharmacology systemically describes the pharmacological mechanisms of Zhisousan in the treatment of chronic cough and suggests they are associated with multiple signaling pathways such as hepatitis B, Kaposi sarcoma-associated herpesvirus infection, microRNAs in cancer, non-small cell lung cancers, P53 signaling pathway, and apoptosis.