Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice.
10.3760/cma.j.cn501113-20200910-00509
- Author:
Ming Yue HAO
1
;
Lin Lin SUN
2
;
Ming Wei SHENG
3
;
Jing Shu LYU
4
;
Yuan Bang LIN
5
;
Yu Hua YANG
4
;
Jia Hao ZHI
4
;
Wen Li YU
3
;
Hong Yin DU
5
Author Information
1. Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300192, China Hao Mingyue is working on the Department of Anesthesiology, Tianjin Eye Hospital, Tianjin 300020, China.
2. Department of Anesthesiology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, China.
3. Department of Anesthesiology, Tianjin First Center Hospital, School of Medical, Nankai University, Tianjin 300192, China.
4. Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300192, China.
5. Department of General Surgery, General Hospital, Tianjin Medical University, Tianjin 300052, China.
- Publication Type:Randomized Controlled Trial, Veterinary
- Keywords:
Berberine;
Metabolic associated fatty liver disease;
Necroptosis;
Nuclear-factor erythroid 2-related factor 2
- MeSH:
Animals;
Berberine/therapeutic use*;
Fatty Liver;
Male;
Mice;
Mice, Inbred C57BL;
NF-E2-Related Factor 2/metabolism*;
Necrosis
- From:
Chinese Journal of Hepatology
2022;30(2):224-229
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
