The mechanism of Dange Jiecheng decoction improving alcoholic liver disease in a rat model
- VernacularTitle:丹葛解酲汤对酒精性肝病大鼠模型的改善作用及其机制分析
- Author:
Sujun GUO
1
;
Bo ZHOU
1
;
Li MA
1
Author Information
- Publication Type:Journal Article
- Keywords: Liver Diseases， Alcoholic; Dan Ge Jie Cheng Decoction; Ferroptosis; P53/GPX4; Rats， Sprague-Dawley
- From: Journal of Clinical Hepatology 2025;41(11):2351-2358
- CountryChina
- Language:Chinese
- Abstract: ObjectiveTo investigate the effect of Dange Jiecheng decoction in improving alcoholic liver disease （ALD） in rats， as well as its mechanism of action based on the tumor protein P53/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsA total of 36 male Sprague-Dawley rats were randomly divided into normal group， model group， Dange Jiecheng decoction group， and compound Yiganling tablets group， with 9 rats in each group. The rats were given gradient intragastric administration of 56% alcohol to establish a model of ALD， and meanwhile， the corresponding drug was given by gavage for 12 consecutive weeks. After the experiment ended， serum and liver tissue samples were collected to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） and the levels of malondialdehyde （MDA）， reactive oxygen species （ROS）， glutathione （GSH）， and Fe2+； HE staining was used to observe histopathological changes， and oil red O staining and Prussian blue staining were used to observe fat and iron deposition in liver tissue， respectively； RT-qPCR and Western blot were used to measure the mRNA and protein expression levels of P53， glutathione peroxidase 4 （GPX4）， NADPH oxidase 1 （NOX1）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and ferritin heavy chain 1 （FTH1） in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the model group had disordered arrangement and incomplete structure of hepatocytes with inflammatory cell infiltration and a large number of fat vacuoles， significant increases in the serum levels of AST， ALT， TG and the levels or activities of MDA， ROS， and Fe2+ in liver tissue （all P<0.01）， significant increases in the mRNA and protein expression levels of P53， NOX1， and PTGS2 （all P<0.01）， and significant reductions in the content of GSH in serum and the mRNA and protein expression levels of GPX4 and FTH1 in liver tissue （all P<0.01）. Compared with the model group， the Dange Jiecheng decoction group and the compound Yiganling tablets group had ordered arrangement of hepatocytes with a reduction in inflammation， significant reductions in the serum levels of AST， ALT， and TG， the levels of MDA， ROS， and Fe2+ in liver tissue， and the mRNA and protein expression levels of P53， NOX1， and PTGS2 in liver tissue （all P<0.05）， and significant increases in the content of GSH in serum and the mRNA and protein expression levels of GPX4 and FTH1 in liver tissue （all P<0.05）， as well as an improvement in hepatic steatosis and a reduction in iron deposition （all P<0.01）. ConclusionDange Jiecheng decoction can effectively improve disease progression in rats with ALD， possibly by regulating the P53/GPX4 pathway and inhibiting ferroptosis.
