Inhibition of glutathione reductase by plant polyphenols.
The effects of forty-one plant polyphenols on the activity of glutathione reductase (GSH-RD) were studied. These polyphenols showed varying degrees of concentration-dependent inhibition on the enzyme, with IC50 values that varied from approximately 40 microM to 1 mM. 4'-Hydroxychalcone and tannic acid were among the more potent inhibitors, with IC50 values of 47.3 and 50.4 microM, respectively. Different classes of polyphenols varied in potency in the following order: chalcones > tannic acid > flavonoids > coumarins > catechins. Analysis of structure-activity relationships showed certain chemical structures to be important for the inhibition of GSH-RD: (a) C-5 and C-7 hydroxylations in the A-ring, a carbonyl group at C-4, and the B-ring attached to C-2 in flavonoids; (b) C-2' and C-4' hydroxylations in chalcones; and (c) C-6 and C-7 hydroxylations in coumarins. The inhibition of GSH-RD by tannic acid and quercetin was time dependent and irreversible, whereas that by 4'-hydroxychalcone and esculin was reversible but not time dependent. Enhanced inhibition of GSH-RD by the four polyphenols 4'-hydroxychalcone, quercetin, butein, and acacetin was observed in the presence of NADPH. Kinetic studies showed that both tannic acid and 4'-hydroxychalcone exhibited non-competitive inhibition on GSH-RD towards glutathione disulfide.
Zhang
K
K
Department of Experimental Surgery, Singapore General Hospital, Singapore. geskai@sgh.gov.sg
Yang
E B
EB
Tang
W Y
WY
Wong
K P
KP
Mack
P
P
D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D009249:NADP / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D009249:NADP; D005980:Glutathione Reductase