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The essential target was selected by using Cytoscape to analyze the topological network of potential targets. Furthermore, we constructed a preliminary molecule docking study to explore the binding site by Surflex\u2010Dock suite SYBYL X 2.0. The DAVID database was selected for gene functional annotations and KEGG enrichment analysis. Moreover, we demonstrated the ameliorating effect of emodin on carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced liver injury in mice. We also verified the network predictions in vitro via various techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The collected results showed that 35 targets were related to emodin, and 6,198 targets were associated with liver fibrosis. The Venn analysis revealed that 17 intersection targets were correlated with emodin anti\u2010liver fibrosis. The topological network analysis suggested that the p53 was the remarkable crucial target. Besides, the molecule docking results showed that emodin could directly interact with p53 by binding the active site residues ASN345, GLN331, and TYR347. Finally, KEGG pathway enrichment results indicated that essential genes were mainly enriched in mitogen\u2010activated protein kinase (MAPK) signaling pathways. Moreover, our study confirmed that emodin alleviated CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury in mice, inducing hepatic stellate cells (HSCs) apoptosis via regulating the p53\/ERK\/p38 axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study partially verified the network pharmacological prediction of emodin inducing HSCs cell apoptosis through the p53\/ERK\/p38 axis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iub.2523","type":"journal-article","created":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T09:19:27Z","timestamp":1624699167000},"page":"1166-1179","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The mechanism research on the anti\u2010liver fibrosis of emodin based on network pharmacology"],"prefix":"10.1002","volume":"73","author":[{"given":"Baoyu","family":"Liang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Pharmacology and Safety 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