Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation.
This study examined the effects of metabolic transformation of the common dietary flavonoid, quercetin, on its ability to protect low-density lipoprotein (LDL) from neutrophil-mediated modification. Quercetin was shown to be effective in protecting LDL against neutrophil-mediated modification at physiological concentrations (1 microM) and appears to act by inhibiting myeloperoxidase (MPO)-catalyzed oxidation (IC(50) = 1.0 microM). Quercetin was also shown to protect against radical-induced [2,2'-azobis(2-methylpropionamidine)dihydrochloride] oxidation (IC(50) = 1.5 microM). Studies of structure-activity relationships showed that methylation at the 3'-position or glucuronidation at the 3-position did not significantly affect inhibition by quercetin of the MPO activity, but conjugations at both positions significantly reduce its activity. Our results suggest that the common dietary flavonoid, quercetin, and some of its major in vivo metabolites are potential inhibitors of MPO at physiological concentrations. Dietary flavonoids that could modify MPO activity could protect lipoproteins from damage in chronic inflammatory states such as cardiovascular disease.
Loke
Wai Mun
WM
School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital Unit, Medical Research Foundation Building, Level 4, 50 Murray Street, Perth, WA 6000, Australia.
Proudfoot
Julie M
JM
McKinley
Allan J
AJ
Needs
Paul W
PW
Kroon
Paul A
PA
Hodgson
Jonathan M
JM
Croft
Kevin D
KD
D004791:Enzyme Inhibitors / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000037:antagonists & inhibitors; D011794:Quercetin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D013481:Superoxides; D011794:Quercetin; D009195:Peroxidase; D019255:NADPH Oxidases