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Int Immunopharmacol. 2018 Aug;61:266-276. doi: 10.1016/j.intimp.2018.06.008. Epub 2018 Jun 11.

Protective effects of ginsenoside Rg1 against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice through inhibiting toll-like receptor 4 signaling pathway.

Author information

1
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.
2
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China.
3
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China. Electronic address: qiangmeng@dlmedu.edu.cn.
4
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Key Laboratory of Pharmacokinetics and Transport of Liaoning Province, Dalian Medical University, Dalian 116044, China. Electronic address: kexinliu@dlmedu.edu.cn.

Abstract

Acute liver injury (ALI) is a dramatic liver disease characterized by large areas of inflammation in the liver. This study aimed to investigate the protective effects of ginsenoside Rg1 (Rg1), a biologically active component in Panax ginseng, on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI in mice, and meanwhile explore the molecular mechanism in vivo and in vitro. Mice were pretreated with Rg1 for three days prior to LPS (40 μg/kg)/D-GalN (700 mg/kg) administration. The results showed that Rg1 improved the survival rate and reduced the liver to body weight ratios in mice. Rg1 also reduced the production of oxidative markers such as MDA and MPO induced by LPS/D-GalN. In addition, Rg1 significantly decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-1β, Mip-2, Mcp-1, iNOS, and increased the activity of anti-inflammatory cytokine IL-10. Moreover, Rg1 inhibited the protein expression of TLR4 and its downstream genes including NF-κB and MAPKs, which are involved in inflammatory response. Rg1 dramatically reduced oxidative stress by regulating the expression of efflux transporters Mrp2 and various enzymes including GCLC, GCLM, HO-1 and NQO1. However, the changes in these genes and protein induced by Rg1 were abrogated by TLR4 antagonist TAK-242 in vitro. In conclusion, Rg1 had hepatoprotective effect on LPS/D-GalN-induced ALI in mice. The protection may be associated with the inhibition of TLR4. These findings suggest that Rg1 may be a promising agent for prevention against ALI.

KEYWORDS:

Acute liver injury; Ginsenoside Rg1; Inflammation response; Lipopolysaccharide/d-galactosamine; Oxidative stress; Toll like receptor 4

PMID:
29902710
DOI:
10.1016/j.intimp.2018.06.008
[Indexed for MEDLINE]

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