Antioxidant properties of isotorachrysone isolated from Rhamnus nakaharai.
Isotorachrysone inhibited iron-induced lipid peroxidation with an IC50 value of 1.64 +/- 0.08 microM in rat brain homogenates, and was comparable in potency to butylated hydroxytoluene and was more potent than alpha-tocopherol or desferrioxamine. The mechanism of antioxidant properties were then examined. Isotorachrysone could scavenge the stable free radical diphenyl-p-picrylhydrazyl. And it was an efficient direct scavenger of water-soluble peroxyl radicals with stoichiometry factor of 0.53 +/- 0.05 in the aqueous phase and also toward lipid-soluble peroxyl radicals in tissue homogenates. The oxygen consumption during peroxidation induced by radicals on human erythrocyte ghosts was suppressed by isotorachrysone. Furthermore, it was reactive towards superoxide anion with a second-order rate constant of 5.06 +/- 0.65 x 10(5) M-1 S-1. But it did not react with hydrogen peroxide detected within the sensitivity limit of our assay. Using ascorbate/iron ion/H2O2 as a hydroxyl radical generating system and deoxyribose as a probe, isotorachrysone was effective with hydroxyl radicals with a second-order rate constant of 3.88 +/- 0.54 x 10(11) M-1 S-1 under stimulation by iron-EDTA. On the other hand, isotorachrysone retarded the peroxidation of human low density lipoprotein (LDL) initiated by both aqueous and lipophilic peroxyl radicals. And it also suppressed copper-catalyzed human LDL oxidation, as measured by fluorescence intensity, electrophoretic mobility, and thiobarbituric acid-reactive substances formation in a concentration-dependent manner. Our results show that isotorachrysone is potentially an effective and versatile antioxidant, and can help protecting LDL against oxidation.
Hsiao
G
G
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ko
F N
FN
Lin
C N
CN
Teng
C M
CM
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D005453:Fluorescence; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010799:Phycoerythrin / Q000378:metabolism; D010944:Plants / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D001391:Azo Compounds; D002614:Chelating Agents; C045076:Fenton's reagent; D016166:Free Radical Scavengers; D005609:Free Radicals; D008077:Lipoproteins, LDL; D009284:Naphthols; D009570:Nitriles; C102504:isotorachrysone; C099252:oxidized low density lipoprotein; C055792:2,2'-azobis(2,4-dimethylvaleronitrile); D010799:Phycoerythrin; D013481:Superoxides; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron