Study on the liver function protective effect and mechanism of ethanol extract from Atractylodes lancea
Objective Based on the network pharmacology and animal experiments,to investigate the protective effect and possible molecular mechanism of ethanol extract from Atractylodes lancea on liver function in mice with liver fibrosis induced by bile duct ligation.Methods The main active ingredients atractylodin,atractylenolide Ⅰ,Ⅱ and Ⅱ from Atractylodes lancea were selected,which had been verified by literature and experiments,and the targets of these active ingredients were obtained through the SwissTargetPrediction database.The liver fibrosis disease targets were obtained through On-line Mendelian Inheritance in Man (OMIM),DisGeNET and GeneCards databases.The targets were added to the Wei Sheng Xin platform to find the intersection target for Atractylodes lancea in treating liver fibrosis.Cytoscape 3.10.1 was used to construct the "drug-component-target-disease" network diagram and protein-protein interaction core target network diagram.GO functional enrichment analysis and KEGG pathway analysis were performed,and molecular docking was performed between active components and core targets.Liver fibrosis was induced in mice by bile duct ligation,and liver function markers were measured.Results A total of 91 corresponding targets of atractylodin,atractylenolide Ⅰ,Ⅱ and Ⅲ and 9296 liver fibrosis disease targets were obtained,including 74 intersecting targets and 31 core targets.KEGG enrichment analysis showed that the main signaling pathways involved included inflammatory pathways such as epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt).Molecular docking results showed that the active ingredients had strong binding activity with the core target protein.The results of animal experiments showed that,compared with the sham surgery group,the model group displayed notable,the liver index,spleen index,activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),degree of liver fibrosis,mRNA and protein expression of α-smooth muscle actin (α-SMA) and recombinant collagen type Ⅰ alpha 1 (COL1A1),and mRNA of recombinant collagen type Ⅳ alpha 2 (COL4A2) were significantly increased,and the thymus index was sigficantly decreased (P<0.05);compared with the model group,the liver injury of mice in the Atractylodes lancea administration group reduced liver injury,its liver index,spleen index,activity of serum ALT and AST,degree of liver fibrosis,mRNA and protein expression of α-SMA and COL1A1,and mRNA of COL4A2 were significantly decreased,and the thymus index was sigficantly increased (P<0.05).Conclusion Atractylodes lancea can improve liver function and alleviate tissue pathological damage in mice with liver fibrosis,which may be related to activating pathways such as PI3K/Akt,inhibiting oxidative stress and inflammatory reactions,and intervening in liver fibrosis.
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