Effect of ganoderic acid A on a mouse model of concanavalin A-induced acute immune liver injury and its mechanism
Journal Title: Journal of Clinical Hepatology - Year 2024, Vol 40, Issue 12
Abstract
[Objective] To investigate the therapeutic effect of ganoderic acid A （GA-A） on a mouse model of concanavalin A （ConA）-induced autoimmune hepatitis （AIH）. [Methods] A total of 35 mice were randomly divided into control group （NC group）， model group （ConA group）， and low-， middle-， and high-dose GA-A treatment groups （GA-A-L， GA-A-M， and GA-A-H groups， respectively）， with 7 mice in each group. ConA was injected via the caudal vein of mice to establish a classic mouse model of AIH， and different doses of GA-A were administered via intraperitoneal injection 1 hour later for treatment. Proteomic techniques were used to investigate the protective mechanism of GA-A on hepatocytes， and HL-60 cells were differentiated into dHL-60 neutrophils by all-trans retinoic acid in vitro to validate the mechanism of action of GA-A. Related indicators were measured， including inflammatory markers （the activities of serum alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］， HE staining， and inflammation-related genes）， apoptosis markers （TUNEL staining）， neutrophils， and neutrophil extracellular trap （NET） markers （myeloperoxidase ［MPO］， citrullinated histone H3 ［CitH3］， Ly6G， and free double-stranded DNA ［dsDNA］）， and p38 phosphorylation markers. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. [Results] Compared with the NC group， the ConA group had significant increases in the serum levels of ALT and AST （both P<0.001）， and compared with the ConA group， GA-A treatment significantly reduced the levels of ALT and AST （both P<0.01）. HE staining showed that the mice in the ConA group had significant liver necrosis， while GA-A treatment significantly reduced the area of liver necrosis and the number of TUNEL-positive cells （both P<0.05）. Compared with the ConA group， the GA-A group had significant reductions in the expression levels of the inflammatory factors interleukin-6， tumor necrosis factor-α， and interferon gamma in serum and liver tissue （all P<0.05）. The proteomic analysis showed that GA-A alleviated ConA-induced acute immune liver injury by inhibiting the release of NET and the p38 MAPK pathway. Immunofluorescent staining of mouse liver tissue showed that compared with the ConA group， the GA-A group had significant reductions in the number of MPO-positive neutrophils and the number of cells with positive Ly6G and CitH3 （all P<0.01）. Western Blot and dsDNA testing showed that GA-A significantly inhibited the levels of the NET markers dsDNA and CitH3 and the level of p38 phosphorylation in liver tissue and dHL-60 cells （all P<0.05）. [Conclusion] GA-A alleviates liver inflammatory response and hepatocyte death by inhibiting the p38 MAPK pathway and the release of NET， thereby alleviating ConA-induced acute immune liver injury. This study provides a theoretical basis for the use of GA-A to treat immune liver injury by regulating neutrophil function.
Authors and Affiliations
Yi CUI, Fengjie QIAO, Jiahao QIU, Yufei LIU, Zhujun GAO, Zhi SHANG, Yueqiu GAO
Keywords
Related Articles
- EP ID EP753954
- DOI 10.12449/JCH241211
- Views 23
- Downloads 0
The role of CD8+ T cells in nonalcoholic steatohepatitis
Nonalcoholic steatohepatitis （NASH） is a liver disease closely associated with metabolic syndrome， and its pathogenesis includes insulin resistance， lipid metabolism disorders， and inflammatory response. This articl...
Influence of metabolism-related factors on the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure and establishment of a predictive model
[Objective] To investigate the influence of metabolism-related factors （overweight and/or obesity， hyperglycemia， hypertension and dyslipidemia）on the 90-day prognosis of patients with hepatitis B virus-related acute...
Hotspots and challenges in blocking the mother-to-child transmission of hepatitis B virus
Chronic hepatitis B virus （HBV） infection remains a major public health challenge in China， affecting over 70 million people and posing great challenges to the prevention and control of the disease. At present， both...
Systemic therapy for advanced hepatocellular carcinoma
Hepatocellular carcinoma （HCC） is one of the most common malignancies with high morbidity and mortality rates worldwide. With the advances in molecular biology and tumor immunology， molecular-targeted agents represent...
Efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with advanced hepatocellular carcinoma
[Objective] To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma （HCC）. [Methods...