title: Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells.
abstract: Many epidemiologic studies have reported that dietary flavonoids provide protection against cardiovascular disease. Quercetin, a member of the bioflavonoids family, has been proposed to have anti-inflammatory, anti-atherogenic, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. Recent studies demonstrated that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore, we examined the effect of chemically synthesized quercetin glucuronide on platelet-derived growth factor (PDGF)-induced cell migration and kinase activation in cultured rat aortic smooth muscle cells (RASMCs). PDGF-induced RASMC migration was inhibited by quercetin 3-O-beta-D-glucuronide (Q3GA). Q3GA also attenuated PDGF-induced cell proliferation in RASMCs. PDGF activated extracellular-signal regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and Akt in RASMCs. PDGF-induced JNK and Akt activations were suppressed by Q3GA, whereas ERK1/2 and p38 MAP kinase activations were not affected. We also confirmed that PDGF-induced JNK and Akt activations were inhibited by antioxidants, N-acetylcysteine and diphenyleneiodonium chloride, in RASMCs. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may possess preventing effects for cardiovascular diseases relevant to vascular smooth muscle cell disorders.
authors.affiliation: Department of Pharmacology, Institute of Health Bioscience, University of Tokushima Graduate School, Kuramoto, Japan. ikeisuke@basic.med.tokushima-u.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa-Ishizawa
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Motobayashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hamano
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minakuchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020719:Glucuronides / Q000737:chemistry / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D020719:Glucuronides; D010982:Platelet-Derived Growth Factor; D011794:Quercetin; D048670:MAP Kinase Kinase 4