Therapeutic efficacy and mechanism of action of ginsenoside Rg1 in treating acute hepatic failure in mice
10.3760/cma.j.issn.1007-3418.2017.03.011
- VernacularTitle: 人参皂苷Rg1对小鼠急性肝衰竭的治疗作用和机制研究
- Author:
Huan LUO
1
;
Wenxiang HUANG
;
Cheng YANG
;
Jinqiu ZHAO
;
Shu LIU
;
Yashu XU
;
Chengwei LIU
Author Information
1. Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
- Publication Type:Journal Article
- Keywords:
Mice;
Apoptosis;
Liver failure;
Gensenoside Rg1;
Endoplasmic reticulum stress
- From:
Chinese Journal of Hepatology
2017;25(3):217-222
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To examine the regulatory effect of ginsenoside Rg1 (G-Rg1) on endoplasmic reticulum stress and its effect on hepatocellular apoptosis in carbon tetrachloride (CCl4)-induced acute liver failure (ALF).
Methods:Forty healthy, adult male C57/BL mice were randomly divided into normal saline control (NS) group, G-Rg1 blank control (G-Rg1) group, CCl4 model (CCl4) group, and G-Rg1 preventive treatment (CCl4+G-Rg1) group, and an ALF mouse model was established by CCl4 induction. Blood and liver specimens were collected from all mice upon sacrifice at 12 hours post-intraperitoneal injection. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined using commercial test kits. The mRNA expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) was measured using real-time PCR. The protein expression of GRP78, CHOP, caspase12, and caspase3 were measured by Western blot. Histological changes in the liver were assessed by hematoxylin-eosin staining, and the expression of GRP78 and caspase3 was detected by immunohistochemistry. Hepatocyte apoptosis was determined using terminal transferase dUTP nick end labeling. Quantitative data were analyzed using one-way ANOVA, and subsequent pairwise comparisons were performed using the LSD-t method.
Results:Serum ALT, AST, and TBil levels in the CCl4+G-Rg1 group were significantly reduced compared with those in the CCl4 group (ALT: 691.30 ± 108.06 U/L vs 980.66 ± 110.29 U/L, F = 365.07, P < 0.05; AST: 195.40 ± 15.41 U/L vs 319.44 ± 89.32 U/L, F = 115.64, P < 0.05; TBil: 1.09 ± 0.11 mg/dl vs 1.56 ± 0.12 mg/dl, F = 211.29, P < 0.05). The relative mRNA expression of GRP78 and CHOP was significantly lower in the CCl4 + G-Rg1 group than in the CCl4 group (P < 0.05). The relative protein expression of caspase3, GRP78, caspase12, and CHOP was significantly reduced to different extents in the CCl4+G-Rg1 group compared with those in the CCl4 group (P < 0.05). The CCl4 + G-Rg1 group showed reduced liver tissue degeneration and necrosis compared with the CCl4 group. Furthermore, the CCl4+G-Rg1 group showed significantly fewer brown granules in the liver than the CCl4 group (P < 0.05), indicating that G-Rg1 preventive treatment reduced CCl4-induced hepatocyte apoptosis.
Conclusion:G-Rg1 prophylaxis can inhibit inflammation and reduce hepatocyte necrosis and apoptosis during CCl4-induced ALF. Its mechanism may involve the suppression of endoplasmic reticulum stress-related signaling molecules to alleviate hepatocyte endoplasmic reticulum stress and apoptosis. The results of this study suggest that G-Rg1 may inhibit liver inflammation and hepatocyte apoptosis through multiple targets to protect liver function.
