Dissecting the underlying pharmaceutical mechanism of Danggui Buxue decoction acting on idiopathic pulmonary fibrosis with network pharmacology

摘要

Backgroud:Danggui Buxue decoction(DBD),a classical prescription in traditional Chinese medicine,has been found to have protective effect on bleomycin-induced pulmonary fibrosis in rats by reducing alveolar inflammation and fibrosis.However,the biological activity of individual chemical components and mechanism of action of whole formula are not clear.Methods:Potential targets of active ingredients of DBD were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SymMap database.Target genes related to idiopathic pulmonary fibrosis were obtained from the Online Mendelian Inheritance in Man database,Therapeutic Targets Database and Gkb database.Then,the common targets were obtained by overlapping the potential targets of active ingredients in DBD and diseases related targets.The selected targets were subjected to Kyoto Encyclopedia of Genes and Genomes signaling pathway and Gene Ontology analysis,and the network map of active component-target-pathway was established using Cytoscape 3.7.1 software.The active components of DBD with most targets were selected for fibrosis-related marker verification.The mRNA and protein expression of fibrosis markers,α-smooth muscle actin,collagen 1 and fibronectin,were detected in TGF-β1-induced fibroblast cell line after treatment with the active components.Results:The 14 active ingredients,such as quercetin and kaempferol,were screened from DBD.It acts on 26 targets like estrogen receptor 2 and prostaglandin-endoperoxide synthase 2,and mainly involves 38 signaling pathways such as cell inflammation and autophagy.Kaempferol and quercetin are the two compounds with the highest network regulation,which can inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of fibrosis markersα-smooth muscle actin,collagen 1 and fibronectin.Conclusion:The integration mode of multi-component,multi-target,multi-channel and mechanism of DBD in the treatment of idiopathic pulmonary fibrosis are predicted by means of network pharmacology.Our study could indicate the direction of further anti-fibrotic mechanism research.