A flavone from Manilkara indica as a specific inhibitor against aldose reductase in vitro.
Isoaffinetin (5,7,3',4',5'-pentahydroxyflavone-6-C-glucoside) was isolated from Manilkara indica as a potent inhibitor of lens aldose reductase by bioassay-directed fractionation. This C-glucosyl flavone showed specific inhibition against aldose reductases (rat lens, porcine lens and recombinant human) with no inhibition against aldehyde reductase and NADH oxidase. Kinetic analysis showed that isoaffinetin exhibited uncompetitive inhibition against both dl-glyceraldehyde and NADPH. A structure-activity relationship study revealed that the increasing number of hydroxy groups in the B-ring contributes to the increase in aldose reductase inhibition by C-glucosyl flavones.
Haraguchi
Hiroyuki
H
Faculty of Life Science and Biotechnology, Fukuyama University, Gakuen-cho, Fukuyama 729-0292, Japan. haragu@bt.fubt.fukuyama-u.ac.jp
Hayashi
Ryosuke
R
Ishizu
Takashi
T
Yagi
Akira
A
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D032129:Manilkara; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D051381:Rats; D013329:Structure-Activity Relationship; D013552:Swine
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; D000449:Aldehyde Reductase