Protective Effect of <i>Codonopsis lanceolata</i> Root Extract Against Alcoholic Fatty Liver in the Rat

Abstract

Alcohol intake remains the most important cause of fatty liver throughout the world. The current study was undertaken to determine whether dietary supplementation with Codonopsis lanceolata root water extract attenuates the development of alcoholic fatty liver in rats and to elucidate the molecular mechanism for such an effect. Male Sprague-Dawley rats were fed normal diet (ND), ethanol diet (ED) (36% of total energy from ethanol), or 0.5% C. lanceolata root extract-supplemented ethanol diet (ED+C) for 8 weeks. C. lanceolata root water extract supplemented to rats with chronic alcohol consumption ameliorated the ethanol-induced accumulations of hepatic cholesterol and triglyceride. Chronic alcohol consumption up-regulated the hepatic expression of genes involved in inflammation, fatty acid synthesis, and cholesterol metabolism, including tumor necrosis factor alpha (TNFalpha), liver X receptor alpha (LXRalpha), sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase, acetyl-coenzyme A carboxylase alpha (ACC), stearoyl-coenzyme A desaturase 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), and low-density lipoprotein receptor (LDLR). The ethanol-induced up-regulations of TNFalpha, LXRalpha, SREBP-1c, HMGR, and LDLR genes in the liver were reversed by feeding C. lanceolata root water extract for 8 weeks. Moreover, ethanol-induced decreases in the ratio of phospho-5'-AMP-activated protein kinase (AMPK) alpha/AMPKalpha and phospho-ACC/ACC protein levels in the liver were significantly restored (135% and 35% increases, respectively, P < .05) by supplementing them with C. lanceolata root water extract. In conclusion, C. lanceolata root water extract appears to be protective against alcoholic fatty liver through the regulation of SREBP-1c, LXRalpha, HMGR, and LDLR genes and by the phosphorylation of AMPKalpha and ACC, which are implicated in lipid metabolism.