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Environ Toxicol. 2018 Oct;33(10):1050-1060. doi: 10.1002/tox.22616. Epub 2018 Jul 2.

Hepatoprotective effect of ginsenoside Rg1 from Panax ginseng on carbon tetrachloride-induced acute liver injury by activating Nrf2 signaling pathway in mice.

Ning C1, Gao X1, Wang C1,2, Huo X1,2, Liu Z1,2, Sun H1,2, Yang X1,2, Sun P1,2, Ma X1,2, Meng Q1,2, Liu K1,2.

Author information

1
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.
2
Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.

Abstract

Oxidative stress and inflammatory response are well known to be involved in the pathogenesis of acute liver injury. This study was performed to examine the hepatoprotective effect of ginsenoside Rg1 (Rg1) against CCl4 -induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway in vivo and in vitro. Mice were orally administered Rg1 (15, 30, and 60 mg/kg) or sulforaphane (SFN) once daily for 1 week prior to 750 μL/kg CCl4 injection. The results showed that Rg1 markedly altered relative liver weights, promoted liver repair, increased the serum level of TP and decreased the serum levels of ALT, AST and ALP. Hepatic oxidative stress was inhibited by Rg1, as evidenced by the decrease in MDA, and increases in GSH, SOD, and CAT in the liver. Further research demonstrated that Rg1 suppressed liver inflammation response through repressing the expression levels of inflammation-related genes including TNF-α, IL-1β, IL-6, COX-2, and iNOS. In addition, Rg1 enhanced antioxidative stress and liver detoxification abilities by up-regulating Nrf2 and its target-genes such as GCLC, GCLM, HO-1, NQO1, Besp, Mrp2, Mrp3, Mrp4, and down-regulating Cyp2e1. However, the changes in Nrf2 target-genes, as well as ameliorative liver histology induced by Rg1 were abrogated by Nrf2 antagonist all-transretinoic acid in vivo and Nrf2 siRNA in vitro. Overall, the findings indicated that Rg1 might be an effective approach for the prevention against acute liver injury by activating Nrf2 signaling pathway.

KEYWORDS:

acute liver injury; carbon tetrachloride (CCl4); inflammation response; nuclear factor erythroid-2-related factor 2 (Nrf2); oxidative stress

PMID:
29964319
DOI:
10.1002/tox.22616
[Indexed for MEDLINE]

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