Mechanism of Ginsenoside Rg1 in Alleviating Alcohol-induced Liver Injury in Tree Shrews via Activating of Nrf2 Pathway  and Inhibiting of Mitochondrial Apoptosis

Jintao LI; Tianyong XU; Yanli HU; Yuexin HU; Shengxiong HONG; Yu LU; Jishuai CHENG; Li XU

doi:10.12259/j.issn.2095-610X.S20261002

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Jintao LI, Tianyong XU, Yanli HU, Yuexin HU, Shengxiong HONG, Yu LU, Jishuai CHENG, Li XU. Mechanism of Ginsenoside Rg1 in Alleviating Alcohol-induced Liver Injury in Tree Shrews via Activating of Nrf2 Pathway and Inhibiting of Mitochondrial Apoptosis[J]. Journal of Kunming Medical University. doi: 10.12259/j.issn.2095-610X.S20261002

Citation:

Jintao LI, Tianyong XU, Yanli HU, Yuexin HU, Shengxiong HONG, Yu LU, Jishuai CHENG, Li XU. Mechanism of Ginsenoside Rg1 in Alleviating Alcohol-induced Liver Injury in Tree Shrews via Activating of Nrf2 Pathway and Inhibiting of Mitochondrial Apoptosis[J]. Journal of Kunming Medical University. doi: 10.12259/j.issn.2095-610X.S20261002

Citation:

Jintao LI, Tianyong XU, Yanli HU, Yuexin HU, Shengxiong HONG, Yu LU, Jishuai CHENG, Li XU. Mechanism of Ginsenoside Rg1 in Alleviating Alcohol-induced Liver Injury in Tree Shrews via Activating of Nrf2 Pathway and Inhibiting of Mitochondrial Apoptosis[J]. Journal of Kunming Medical University. doi: 10.12259/j.issn.2095-610X.S20261002

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Mechanism of Ginsenoside Rg1 in Alleviating Alcohol-induced Liver Injury in Tree Shrews via Activating of Nrf2 Pathway and Inhibiting of Mitochondrial Apoptosis

doi: 10.12259/j.issn.2095-610X.S20261002

1.
Department of Laboratory Animal Science
2.
Department of Science and Technology
3.
School of Humanities and Management，Kunming Medical University，Kunming Yunnan 650500，China

Received Date: 2026-05-08
Available Online: 2026-10-10

Abstract

Abstract

Objective To explore the protective effect of ginsenoside Rg1 on alcohol-induced liver injury in tree shrews, and to reveal its molecular mechanism based on the Nrf2 signaling axis and mitochondrial apoptosis pathway, so as to provide new insights for the treatment of alcoholic liver disease. Methods Tree shrews were randomly divided into a control group, an alcohol model group and a ginsenoside Rg1 treatment group（6 animals per group）. The latter two groups were given alcohol by gavage to establish a liver injury model, while the Rg1 group was simultaneously administered ginsenoside Rg1 by gavage for 12 consecutive weeks. Hepatic ultrasonography was used to assess parenchymal changes; serum liver function indicators （ALT, AST）, oxidative stress indicator malondialdehyde （MDA） levels, and the activities of lactate dehydrogenase （LDH） and glutathione peroxidase （GSH-Px） were measured; liver tissue sections were stained with HE to observe the degree of steatosis, inflammatory cell infiltration, and ballooning degeneration; transmission electron microscopy was used to observe changes in mitochondrial ultrastructure; Western Blot was used to detect the expression of Nrf2 pathway proteins （Nrf2, Keap1） and apoptosis-related proteins （Bcl-2, Bax, Cytochrome c, total Caspase-9, total Caspase-3）. Immunohistochemistry was used to detect the protein expression and localization of Keap1, HO-1 and total Caspase-3 in liver tissue. Results Compared with the model group, the ginsenoside Rg1 group showed improved hepatic ultrasound imaging, significantly reduced serum ALT, AST, MDA levels and LDH activity （P < 0.05, F values were 327.57, 218.70, 510.07, and 331.59, respectively）, and significantly increased GSH-Px activity （P < 0.05）. Hepatic steatosis, inflammatory infiltration, and ballooning degeneration were all significantly attenuated; transmission electron microscopy showed repair of mitochondrial ultrastructural damage such as swelling. At the molecular level, ginsenoside Rg1 significantly upregulated Nrf2 expression and downregulated its negative regulator Keap1 （P < 0.05）; immunohistochemistry confirmed that after Rg1 intervention, Keap1-positive signals were weakened and HO-1-positive signals were significantly enhanced （P < 0.05）. Meanwhile, ginsenoside Rg1 increased the expression of the anti-apoptotic protein Bcl-2, decreased the expression of the pro-apoptotic protein Bax, and inhibited Cytochrome c release （P < 0.05）; the expression level of total Caspase-9 （precursor form） increased, and the downward trend in total Caspase-3 （precursor form） expression was reversed （P < 0.05）; immunohistochemistry showed that total Caspase-3-positive signals were significantly weakened in the ginsenoside Rg1 group （P < 0.05）. Conclusion Ginsenoside Rg1 has a definite protective effect against alcohol-induced liver injury in tree shrews. Its mechanism may involve activation of the Nrf2/Keap1/HO-1 antioxidant pathway, improvement of mitochondrial structure, regulation of Bcl-2/Bax balance, and inhibition of the caspase cascade, there by blocking the mitochondrial-dependent apoptosis pathway.
- Ginsenoside Rg1,
- Alcoholic liver disease,
- Tree shrew,
- Nrf2,
- Mitochondrial apoptosis,
- Oxidative stress

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