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PO2-6-1

Protective Effects of Antrodia Cinnamomea on Alcoholic Fatty Liver Disease

[Speaker] Yini Cao:1
[Co-author] Lu Xu:1, Qinyu Wang:1, Yunxia Wang:1, Rong Qi:1
1:Peking University Health Science Center, China

Background: Alcoholic fatty liver disease (AFLD) is a leading chronic liver disease worldwide, but currently there are no effective pharmaceutical interventions for its treatment. Antrodia Cinnamomea (AC), an indigenous fungus in Taiwan, has been used as an anti-alcoholic and liver protective drug, but the mechanisms are not fully understood. ALDH2 is the key enzyme in metabolism of alcohol in the liver, as it can turn the cytotoxic acetaldehyde into the non-toxic acetate. However, the role of ALDH2 in the anti-alcoholic effects of AC remains unknown. This study aimed to reveal the effects and mechanisms of AC on AFLD, and the role of ALDH2 therein.
Methods: To explore in vivo effects of AC on AFLD, mice AFLD model was established by giving C57BL/6J wild type (WT) mice 30% (v/v) ethanol (EtOH) via gavage for 4 weeks to induce AFLD. AC was given to the mice through daily intragastric administration during this 4-week EtOH feeding. Parallel experiments of AC were conducted in aldehyde dehydrogenase 2 (ALDH2) knockout (KO) mice.
To investigate in vitro effects of AC on lipid accumulation induced by EtOH in liver cells, primary hepatocytes isolated from WT or ALDH2 KO mice were incubated with 50 mM ethanol for 24 h together with Alda-1 (an agonist of ALDH2) or AC.
Results: In WT mice with AFLD, AC significantly reduced hepatic lipid deposition, increased protein expression and activity of ALDH2 in the liver, and subsequently decreased acetaldehyde content in the liver. AC also down-regulated mRNA expression of lipogenic and inflammatory genes in the liver. These effects of AC on AFLD disappeared in ALDH2 KO mice. In vitro results show that in WT primary hepatocytes stimulated with EtOH, AC reduced lipid accumulation, increased activity of ALDH2, and down-regulated mRNA expression of lipogenic as well as inflammatory genes, which were all comparable to the effects of Alda-1. These effects of AC disappeared in EtOH treated primary hepatocytes of ALDH2 KO mice.
Conclusions: AC inhibited AFLD via up-regulation of enzyme activity of ALDH2 and acceleration of acetaldehyde metabolism, and suppression of lipogenesis and inflammation in liver.
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