Modulation of the TLR4/MyD88/NF- κ B Pathway by Humulus japonicus Extract Protects Against Alcohol-Induced Liver Injury in a Rat Model

J Med Food. 2021 Jan;24(1):18-27. doi: 10.1089/jmf.2019.4650. Epub 2020 Dec 7.

Abstract

Alcohol induces liver injury related to oxidative stress and inflammatory responses. The purpose of this study was to investigate the hepatoprotective effect of Humulus japonicus extract (HJE) against alcohol-induced liver injury. Furthermore, we investigated the mechanisms of the protective effect of HJE on alcohol-induced liver injury. The pretreatment of HJE decreased the levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, and total cholesterol in the plasma, suppressed the malondialdehyde, myeloperoxidase, and enhanced the activities of superoxide dismutase, glutathione, and catalase. The inhibitory effect of HJE against oxidative stress may be associated with the upregulation of nuclear factor erythroid 2-related factor 2 and its target gene heme oxygenase-1. Moreover, HJE inhibited the pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta) by downregulating toll-like receptor 4, myeloid differentiation primary response 88, and nuclear factor kappa B p65. These findings provide evidence for the elucidation of the hepatoprotective mechanisms for HJE.

Keywords: Humulus japonicus extracts; TLR4; liver damage; oxidative stress.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Chemical and Drug Induced Liver Injury, Chronic / drug therapy*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Humulus / chemistry*
  • Liver / metabolism
  • Myeloid Differentiation Factor 88 / metabolism*
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Plant Extracts / therapeutic use*
  • Rats
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism*
  • Transcription Factor RelA / metabolism*

Substances

  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Plant Extracts
  • Rela protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Alanine Transaminase