HIMH0021 attenuates ethanol-induced liver injury and steatosis in mice.

Abstract

Chronic alcohol consumption causes alcohol-induced lipogenesis and promotes hepatic injury by preventing the oxidation of hepatocellular fatty acids through the suppression of the activation of AMP-activated protein kinase (AMPK). HIMH0021, an active flavonoid compound, which is a component of the Acer tegmentosum extract, has been shown to protect against liver damage caused by alcohol consumption. Therefore, in this study, we aimed to determine whether HIMH0021 could regulate alcoholic fatty liver and liver injury in mice. Oral administration of 10 days of Lieber-DeCarli ethanol plus a single binge of 30% ethanol (chronic-plus-binge model) induced steatosis and liver injury and inflammation in mice, which appears similar to the condition observed in human patients with alcohol-related diseases. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

• Authors: Yongjun Lee, Dong-Joo Kwon, Young Han Kim, Moonjin Ra, Seong Il Heo, Won Gyeong Ahn, Jeong-Ran Park, Seoung Rak Lee, Ki Hyun Kim, Sun Young Kim
• Journal: PloS one (PLoS One) Vol. 12 Issue 11 Pg. e0185134 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 29091708 (Publication Type: Journal Article)

Chemical References

• Adiponectin
• Flavones
• Glycosides
• HIMH0021
• Tumor Necrosis Factor-alpha
• Ethanol
• Adenylate Kinase

Topics

• Adenylate Kinase (metabolism)
• Adiponectin (metabolism)
• Animals
• Ethanol (toxicity)
• Fatty Liver (prevention & control)
• Feeding Behavior
• Flavones (pharmacology)
• Glycosides (pharmacology)
• Lipid Metabolism
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)