Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK

Life Sci. 2013 Nov 4;93(18-19):693-9. doi: 10.1016/j.lfs.2013.09.014. Epub 2013 Sep 21.

Abstract

Aims: This study investigated the hepatoprotective effects of low doses of curcumin against liver damage induced by chronic alcohol intake and a high-fat diet. We also examined several potential underlying mechanisms including action on alcohol metabolism, antioxidant activity, AMPK level and lipid metabolism.

Main method: Alcohol (25% v/v, 5 g/kg body weight) was orally administered once a day for 6 weeks to mice fed a high-fat diet with or without two different doses of curcumin (0.02% and 0.05%, wt/wt).

Key findings: Curcumin significantly decreased the plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities (p<0.05) and prevented hepatic steatosis compared with the alcohol control group. Curcumin significantly reversed the alcohol-induced inhibition of the alcohol dehydrogenase, aldehyde dehydrogenase 2 and antioxidant enzyme activities as well as the activation of cytochrome P4502E1 and promotion of lipid peroxidation (p<0.05). Curcumin significantly increased the hepatic total AMPK protein level and concomitantly suppressed the fatty acid synthase and phosphatidate phosphohydrolase activities compared with the alcohol control group (p<0.05). Furthermore, curcumin significantly lowered the plasma leptin, free fatty acids and triglycerides levels and hepatic lipid levels (p<0.05).

Significance: These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating the alcohol metabolic enzyme activity, the antioxidant activity and the lipid metabolism. Therefore, curcumin may provide a promising natural therapeutic strategy against liver disease.

Keywords: Alcohol; Curcumin; Hepatoprotective activity; High-fat diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / physiology*
  • Animals
  • Curcumin / administration & dosage*
  • Cytochrome P-450 CYP2E1 / physiology*
  • Dose-Response Relationship, Drug
  • Ethanol / administration & dosage
  • Ethanol / metabolism*
  • Ethanol / toxicity
  • Liver Diseases, Alcoholic / metabolism*
  • Liver Diseases, Alcoholic / prevention & control*
  • Male
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / physiology
  • Mice
  • Mice, Inbred ICR

Substances

  • Ethanol
  • Cytochrome P-450 CYP2E1
  • AMP-Activated Protein Kinases
  • Curcumin