Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro

Regulatory Toxicology and Pharmacology : RTP
Chenqing NingKe-Xin Liu

Abstract

Acetaminophen (APAP) is a worldwide used drug for treating fever and pain. However, APAP overdose is the leading cause of drug-induced liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of ginsenoside Rg1 (Rg1), the main pharmacologically active compounds of Panax ginseng, against APAP-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway by in vivo and in vitro experiments. Male C57BL/6 mice were treated with Rg1 for 3 days before injection of APAP. Serum and liver tissue samples were collected 6 h later. The results indicated that Rg1 significantly attenuated APAP-induced hepatotoxicity and oxidative stress in a dose-dependent manner. Rg1 effectively enhanced antioxidant and detoxification capacity, which is largely dependent on up-regulating Nrf2 nuclear translocation, reducing Keap1 protein expression and up-regulating Nrf2 target genes including GCLC, GCLM, HO-1, NQO1, Ugt1a1, Ugt1a6, Ugt2b1, Sult2a1, Mrp2, Mrp3 and Mrp4. Furthermore, Rg1 repressed the activities of Cyp2e1, Cyp3a11, Cyp1a2, which are important enzymes in the formation of APAP toxic metabolite N-acetyl-p-benzoquinone imine. However, the changes in transporters and enzymes, as we...Continue Reading

Citations

Mar 6, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Chan MoZhiping Lv
Jun 23, 2021·Journal of Food Biochemistry·Yunfeng BiLei Yu
Aug 2, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Apu ChowdhurySicen Wang

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