Black Carrot (Daucus carota ssp. sativus var. Atrorubens Alef.) Extract Protects against Ethanol-induced Liver Injury via the Suppression of Phosphodiesterase 4 mRNA Expression

Abstract

We examined the protective effects of Black Carrot Extract (BCE) on Alcoholic Liver Disease (ALD) using in vivo and in vitro models. In an in vivo ethanol-Carbon Tetrachloride (CCl4)-treated rat model, BCE treatment suppressed serum alanine aminotransferase and aspartate aminotransferase activity. BCE also suppressed ethanol- and CCl4-induced alcoholic liver disease. Furthermore, we observed that the BCE or butanol-extracted fraction of BCE (BCE-BuOH) recovered the cell viability of in vitro ethanol-treated hepatocytes. BCE-BuOH also suppressed the production of reactive oxygen species induced by ethanol to the control level. Moreover, BCE-BuOH regulated the activities of three alcoholic metabolism-related enzymes: cytochrome P450 2E1 activity was suppressed at the posttranslational level, alcohol dehydrogenase activity was increased at the posttranslational level, and aldehyde dehydrogenase 2 activity was increased at the transcriptional level. Novel findings in this study include an increase in intracellular Cyclic Adenosine 3’,5’-Monophosphate (cAMP) levels in hepatocytes with the simultaneous addition of ethanol and BCE-BuOH and the suppression of changes in the activities of three enzymes upon treatment with an inhibitor of cAMP-dependent protein kinase. Our study also found that BCE-BuOH suppressed the expression of phosphodiesterase 4b mRNA, which increased intracellular cAMP levels. These results suggest that BCE is useful for the treatment of ALD.