Inhibition of xanthine oxidase and suppression of intracellular reactive oxygen species in HL-60 cells by theaflavin-3,3'-digallate, (-)-epigallocatechin-3-gallate, and propyl gallate.
The inhibitory effects of five tea polyphenols, namely theaflavin (TF1), theaflavin-3-gallate (TF2), theaflavin-3,3'-digallate (TF3), (-)-epigallocatechin-3-gallate (EGCG), and gallic acid, and propyl gallate (PG) on xanthine oxidase (XO) were investigated. These six antioxidant compounds reduce oxidative stress. Theaflavins and EGCG inhibit XO to produce uric acid and also act as scanvengers of superoxide. TF3 acts as a competitive inhibitor and is the most potent inhibitor of XO among these compounds. Tea polyphenols and PG all have potent inhibitory effects (>50%) on PMA-stimulated superoxide production at 20 approximately 50 microM in HL-60 cells. Gallic acid (GA) showed no inhibition under the same conditions. At 10 microM, only EGCG, TF3, and PG showed significant inhibition with potency of PG > EGCG > TF3. The superoxide scavenging abilities of these six compunds are as follows: EGCG > TF2 > TF1 > GA > TF3 > PG. PG was the most potent inhibitor of PMA-stimulated H(2)O(2) production in HL-60 cells. The order of H(2)O(2) scavenging ability was TF2 > TF3 > TF1 > EGCG > PG > GA. Therefore, the antioxidative activity of tea polyphenols and PG is due not only to their ability to scavenge superoxides but also to their ability to block XO and related oxidative signal transducers.
Lin
J K
JK
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan. jklin@ha.mc.ntu.edu.tw
Chen
P C
PC
Ho
C T
CT
Lin-Shiau
S Y
SY
D000975:Antioxidants / Q000494:pharmacology; D044946:Biflavonoids; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008956:Models, Chemical; D011435:Propyl Gallate / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D013662:Tea; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D044946:Biflavonoids; D017382:Reactive Oxygen Species; D013662:Tea; D013481:Superoxides; C077197:theaflavin digallate; D005707:Gallic Acid; D011435:Propyl Gallate; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D014969:Xanthine Oxidase