Abstract

Liver fibrosis is an outcome of many chronic liver diseases and often results in cirrhosis, liver failure and even hepatocarcinoma. Zhuyu zhenggan decoction as a classical traditional Chinese medicine formula is used to liver fibrosis in clinical practice while its mechanism is unclear. The aim of this study was to investigate the anti-fibrosis effect of Zhuyu zhenggan decoction and to explore the molecular mechanisms by combining network pharmacology and animal experiment. The carbon tetrachloride-induced liver fibrosis rats were treated with three doses of Zhuyu zhenggan decoction. The liver fibrosis and function were evaluated by histopathological examination and biochemical detection. The fibrosis related protein phosphoinositide 3-kinase, phosphorylated phosphoinositide 3-kinase, protein kinase B and phosphorylated protein kinase B were assessed by Western blot. The herb-component-target network was constructed combined the network pharmacology. Network pharmacology found that 119 potential active compounds were obtained through the analysis of bioavailability and drug-like properties, involving 142 anti-liver fibrosis targets. Gene ontology function enrichment analysis yielded 625 gene ontology entries, most of which were related to biological processes and molecular functions. Kyoto encyclopedia of genes and genomes pathway enrichment screening yielded 117 signal pathways, including phosphoinositide 3 kinase-protein kinase B signal pathway, mitogen-activated protein kinase signal pathway, tumor necrosis factor pathway, etc. Compared with the model group, Zhuyu zhenggan decoction can ameliorate the pathological damage and fibrosis of rat liver tissues, significantly reduce rat serum aminotransferase, aspartate aminotransferase, malondialdehyde levels and significantly increase serum superoxide dismutase levels and can significantly inhibit tumor necrosis factor alpha, interleukin-1 beta and interleukin-6 level. Western blot analysis showed that Zhuyu zhenggan decoction can down-regulate the expression of phosphorylated-phosphoinositide 3-kinase and phosphorylated protein kinase B protein. These results suggested that Zhuyu zhenggan decoction markedly alleviated carbon tetrachloride-induced liver fibrosis by regulating anti-oxidation, inhibiting the expression of pro-inflammatory factors and phosphoinositide 3-kinase-protein kinase B signaling pathway.