Inhibitory effects of Zingiber officinale Roscoe derived components on aldose reductase activity in vitro and in vivo.
Ginger (Zingiber officinale Roscoe) continues to be used as an important cooking spice and herbal medicine around the world. Scientific research has gradually verified the antidiabetic effects of ginger. Especially gingerols, which are the major components of ginger, are known to improve diabetes including the effect of enhancement against insulin-sensitivity. Aldose reductase inhibitors have considerable potential for the treatment of diabetes, without increased risk of hypoglycemia. The assay for aldose reductase inhibitors in ginger led to the isolation of five active compounds including 2-(4-hydroxy-3-methoxyphenyl)ethanol (2) and 2-(4-hydroxy-3-methoxyphenyl)ethanoic acid (3). Compounds 2 and 3 were good inhibitors of recombinant human aldose reductase, with IC50 values of 19.2 +/- 1.9 and 18.5 +/- 1.1 microM, respectively. Furthermore, these compounds significantly suppressed not only sorbitol accumulation in human erythrocytes but also lens galactitol accumulation in 30% of galactose-fed cataract rat model. A structure-activity relationship study revealed that the applicable side alkyl chain length and the presence of a C3 OCH3 group in the aromatic ring are essential features for enzyme recognition and binding. These results suggested that it would contribute to the protection against or improvement of diabetic complications for a dietary supplement of ginger or its extract containing aldose reductase inhibitors.
Kato
Atsushi
A
Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan. kato@med.u-toyama.ac.jp
Higuchi
Yasuko
Y
Goto
Hirozo
H
Kizu
Haruhisa
H
Okamoto
Tadashi
T
Asano
Naoki
N
Hollinshead
Jackie
J
Nash
Robert J
RJ
Adachi
Isao
I
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001555:Benzene Derivatives / Q000302:isolation & purification; D002264:Carboxylic Acids / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D004376:Galactitol / Q000378:metabolism; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013012:Sorbitol / Q000378:metabolism
C514151:2-(4-hydroxy-3-methoxyphenyl)ethanoic acid; C514150:2-(4-hydroxy-3-methoxyphenyl)ethanol; D001555:Benzene Derivatives; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D004376:Galactitol; D013012:Sorbitol; D000449:Aldehyde Reductase; D010626:Phenylethyl Alcohol