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 IC(50) of 10 microM 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.
Muthenna
P
P
Biochemistry Division, National Institute of Nutrition, Hyderabad 500 604, India.
Suryanarayana
P
P
Gunda
Shravan K
SK
Petrash
J Mark
JM
Reddy
G Bhanuprakash
GB
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D015394:Molecular Structure; D013012:Sorbitol / Q000378:metabolism
D000975:Antioxidants; D007527:Isoenzymes; D013012:Sorbitol; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; D003474:Curcumin; D005947:Glucose