Protective Effects of Antrodia cinnamomea and Its Constituent Compound Dehydroeburicoic Acid 32 Against Alcoholic Fatty Liver Disease

Background: Alcoholic fatty liver disease (AFLD), a leading chronic hepatic disease, affects an increasing number of people, and no effective drugs for the treatment of AFLD are available. Antrodia cinnamomea (AC) can inhibit AFLD, but its mechanisms and the effective compound in AC are unknown. Objective: We aimed to explore the anti-AFLD mechanism of AC and the active compound within AC. 10.2174/1874467214666210120152140 Methods: Wild-type (WT) C57BL/6J mice underwent 4 weeks of daily ethanol (EtOH) feeding to induce AFLD. AC or dehydroeburicoic acid 32 (DEA32), a compound in AC, was given to the mice. Parallel experiments to assess the effect of AC were conducted in aldehyde dehydrogenase 2 (ALDH2)-knockout (KO) mice. Primary mouse hepatocytes were incubated with ethanol and Alda-1 (an ALDH2 agonist), AC or DEA32. Results: In WT mice with AFLD, AC reduced lipid deposition, increased the expression and activity of ALDH2, reduced the acetaldehyde content, and downregulated the expression of lipogenic and inflammatory genes in the liver. These effects of AC disappeared in ALDH2 KO mice. DEA32 was identified as an active compound in AC, as its effects on EtOH-treated WT hepatocytes were similar to those of AC, which were comparable to the effects of Alda-1. These effects of DEA32 disappeared in EtOH-treated ALDH2 KO hepatocytes. Furthermore, in WT mice with AFLD, DEA32 reduced lipid deposition, increased the activity of ALDH2, and reduced the accumulation of acetaldehyde in the liver. DEA32 also downregulated the mRNA expression of genes related to lipogenesis and inflammation. Conclusion: AC and its constituent compound DEA32 inhibit AFLD by upregulating ALDH2 activity, accelerating acetaldehyde metabolism, and suppressing lipogenesis and inflammation in the liver.