Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rk1 ameliorates paracetamol-induced hepatotoxicity in mice through inhibition of inflammation, oxidative stress, nitrative stress and apoptosis

  • Hu, Jun-Nan (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Xu, Xing-Yue (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Li, Wei (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Wang, Yi-Ming (College of Animal Science and Technology, Jilin Agricultural University) ;
  • Liu, Ying (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Wang, Zi (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Wang, Ying-Ping (Institute of Special Wild Economic Animals and Plant, CAAS)
  • Received : 2017.02.09
  • Accepted : 2017.07.20
  • Published : 2019.01.15
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Abstract

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, allmice treated with 250mg/kg APAP exhibited severeliverinjury after 24 h, and hepatotoxicitywas assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-$1{\beta}$ compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects.

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References

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