Root bark of Ulmus davidiana var. japonica restrains acute alcohol-induced hepatic steatosis onset in mice by inhibiting ROS accumulation

PLoS One. 2017 Nov 27;12(11):e0188381. doi: 10.1371/journal.pone.0188381. eCollection 2017.

Abstract

Alcohol-induced hepatic steatosis and inflammation are key drivers of alcohol-induced liver injury, mainly caused by oxidative stress. The roots bark of Ulmus davidiana var. japonica is well known for its substantial antioxidative and antitumorigenic potency. In this study, we examined whether this plant can ameliorate alcohol-induced liver injuries characterized by hepatic steatosis and inflammation through its antioxidative activity. C57BL/6J mice were treated with the root bark extract of Ulmus davidiana var. japonica (RUE; 100 mg of extract/kg bodyweight; oral gavage) and alcohol (1 g/kg of bodyweight; oral gavage) for 5 days. Markers of acute alcohol-induced hepatic steatosis were determined and putative molecular mechanisms responsible for the protection of RUE were investigated. RUE noticeably protected against alcohol-induced hepatic steatosis and inflammation. Reactive oxygen species (ROS), over-produced by alcohol, negatively orchestrated various signaling pathways involved in the lipid metabolism and inflammation. These pathways were restored through the ROS scavenging activity of RUE in the liver. In particular, the expression of lipogenic genes (e.g., SREBP-1, ACC, and FAS) and inflammatory cytokines (e.g., IL-1β, and NF-κB p65) significantly decreased with RUE treatment. Conversely, the expression of fatty acid oxidation-related genes (e.g., SIRT1, AMPKα, and PGC1α) were increased in mice treated with RUE. Thus, the results indicate that RUE counteracts and thus attenuates alcoholic hepatic steatosis onset in mice, possibly by suppressing ROS-mediated steatosis and inflammation.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Catechin / analysis
  • Cytokines / metabolism
  • Ethanol
  • Fatty Liver, Alcoholic / drug therapy*
  • Fatty Liver, Alcoholic / genetics
  • Fatty Liver, Alcoholic / pathology
  • Gene Expression Regulation / drug effects
  • Inflammation / pathology
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Liver / drug effects
  • Liver / pathology
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Plant Bark / chemistry*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Roots / chemistry*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Ulmus / chemistry*

Substances

  • Biomarkers
  • Cytokines
  • NF-kappa B
  • Plant Extracts
  • Reactive Oxygen Species
  • Ethanol
  • Catechin
  • Mitogen-Activated Protein Kinases

Grants and funding

The research was supported by the International Science and Business Belt Program through the Ministry of Science, ICT and Future Planning (Grant Number: 2015K000388).