Inhibition of aldose reductase by dietary antioxidant curcumin: Mechanism of inhibition, specificity and significance

Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2) activity has been implicated in the development of various secondary complications of diabetes. In this study we show that curcumin inhibits ALR2 with an IC50 of 10μM in a non-competitive manner, but is a poor inhibitor...

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Bibliographic Details
Published in:FEBS letters 2009-11, Vol.583 (22), p.3637-3642
Main Authors: Muthenna, P., Suryanarayana, P., Gunda, Shravan K., Petrash, J. Mark, Reddy, G. Bhanuprakash
Format: Article
Language:English
Subjects:
AKR
AKR1B10
aldehyde reductase
Aldehyde Reductase - antagonists & inhibitors
Aldehyde Reductase - genetics
Aldehyde Reductase - metabolism
Aldo-keto reductase
aldose reductase inhibitor
ALR1
ALR2
ALR2, AKR1B1
Animals
Antioxidants - administration & dosage
Antioxidants - chemistry
Antioxidants - pharmacology
ARI
Cattle
Curcumin
Curcumin - administration & dosage
Curcumin - chemistry
Curcumin - pharmacology
Dietary Supplements
Dose-Response Relationship, Drug
Erythrocytes - drug effects
Erythrocytes - metabolism
Glucose - pharmacology
HSIR, AKR1B10
human aldose reductase
human small intestine reductase
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - genetics
Isoenzymes - metabolism
Kidney - enzymology
Kinetics
Molecular Structure
RBC
red blood cells
Sorbitol
Sorbitol - metabolism
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Summary:Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2) activity has been implicated in the development of various secondary complications of diabetes. In this study we show that curcumin inhibits ALR2 with an IC50 of 10μM in a non-competitive manner, but is a poor inhibitor of closely-related members of the aldo-keto reductase superfamily, particularly aldehyde reductase. Results from molecular docking studies are consistent with the pattern of inhibition of ALR2 by curcumin and its specificity. Moreover, curcumin is able to suppress sorbitol accumulation in human erythrocytes under high glucose conditions, demonstrating an in vivo potential of curcumin to prevent sorbitol accumulation. These results suggest that curcumin holds promise as an agent to prevent or treat diabetic complications.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2009.10.042