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Rg1 Attenuates alcoholic hepatic damage through regulating AMP-activated protein kinase and nuclear factor erythroid
Yan Gao1, Shi-Feng Chu2, Cong-Yuan Xia1
1a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology , Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Abstract:
Rg1 has shown multiple pharmacological activities and been considered to be evaluated for hepatic protective activity, as Rg1 could modulate different pathways in various diseases. Herein we assessed its effect and potential mechanism in a newly modified ethanol model. C57BL/6 mice were fed with Lieber-DeCarli liquid diet containing ethanol or isocaloric maltose dextrin as control diet with or without Rg1. Meanwhile, bicyclol was treated as positive drug to compare the efficacy of Rg1 against alcoholic hepatotoxicity. According to our data, Rg1 indeed improved the survival rate and lowered the abnormal high levels of serum parameters. H&E and Oil Red O staining indicated that the condition of liver damage was mitigated by Rg1 administration. Furthermore, AMPK and Nrf2 pathways were all modulated at both RNA and protein levels. In accordance with these findings, Rg1 effectively protected against alcoholic liver injury, possibly by modulating metabolism, suppressing oxidative stress, and enhancing oxidant defense systems of Nrf2 pathway. In vitro, Rg1 has no cell toxicity and promotes Nrf2 translocate into nuclear. In summary, we demonstrate that Rg1 is a potent activator of Nrf2 pathway, and could therefore be applied for prevention of hepatic damage.
Insights
Ginsenoside Rg1 (Rg1) effectively protected mice against alcoholic liver injury by modulating metabolism and enhancing the Nrf2 pathway. Rg1 also showed no cell toxicity and promoted Nrf2 nuclear translocation in vitro.
Area of Science:
- Pharmacology
- Hepatology
- Molecular Biology
Background:
- Ginsenoside Rg1 (Rg1) exhibits diverse pharmacological activities.
- Rg1's potential for hepatic protection warrants investigation, particularly in modulating disease pathways.
- Alcoholic liver injury (ALI) remains a significant health concern with complex mechanisms.
Purpose of the Study:
- To assess the protective effects of Rg1 against alcoholic hepatotoxicity in a modified mouse model.
- To elucidate the underlying molecular mechanisms of Rg1's hepatoprotective action.
- To compare Rg1's efficacy with a known drug, bicyclol.
Main Methods:
- C57BL/6 mice were administered an ethanol-containing liquid diet or a control diet, with or without Rg1.
- Histopathological analysis (H&E, Oil Red O) was performed on liver tissues.
- Serum parameters, and RNA/protein levels of AMPK and Nrf2 pathways were analyzed.
- In vitro assays assessed Rg1's cytotoxicity and Nrf2 nuclear translocation.
Main Results:
- Rg1 significantly improved survival rates and normalized elevated serum parameters in ethanol-fed mice.
- Histological examination revealed mitigation of liver damage and lipid accumulation upon Rg1 treatment.
- Rg1 modulated both AMPK and Nrf2 pathways at the RNA and protein levels.
- In vitro studies confirmed Rg1's lack of cytotoxicity and its ability to promote Nrf2 nuclear translocation.
Conclusions:
- Rg1 demonstrates potent protective effects against alcoholic liver injury.
- Rg1 likely exerts its effects by modulating metabolism, reducing oxidative stress, and activating the Nrf2 pathway.
- Rg1 is a promising activator of the Nrf2 pathway for preventing hepatic damage.
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