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

被引：75

作者：

Muthenna, P. ^{[1
]}

Suryanarayana, P. ^{[1
]}

Gunda, Shravan K. ^{[2
]}

Petrash, J. Mark ^{[3
]}

Reddy, G. Bhanuprakash ^{[1
]}

机构：

[1] Jamai Osmania, Div Biochem, Natl Inst Nutr, Hyderabad 500604, Andhra Pradesh, India

[2] Osmania Univ, Bioinformat Ctr, Hyderabad 500007, Andhra Pradesh, India

[3] Univ Colorado, Rocky Mt Lions Eye Inst, Dept Ophthalmol, Aurora, CO USA

来源：

FEBS LETTERS | 2009年 / 583卷 / 22期

关键词：

Aldo-keto reductase; ALR2; AKR1B10; Curcumin; Sorbitol; HUMAN-TISSUES; ALDEHYDE; SORBITOL; END;

D O I：

10.1016/j.febslet.2009.10.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 10 mu M 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. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：3637 / 3642

页数：6

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