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


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Department of Food and Nutrition, Sunchon National University, Suncheon 540-742, Republic of Korea.
Hae-In
HI
Lee
Robin A
RA
McGregor
Myung-Sook
MS
Choi
Kown-Il
KI
Seo
Un Ju
UJ
Jung
Jiyoung
J
Yeo
Myung-Joo
MJ
Kim
Mi-Kyung
MK
Lee
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage*; D019392:Cytochrome P-450 CYP2E1 / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D055372:AMP-Activated Protein Kinases; D003474:Curcumin
Alcohol; Curcumin; Hepatoprotective activity; High-fat diet