Quercetin Glucuronide Inhibits Cell Migration and Proliferation by Platelet-Derived Growth Factor in Vascular Smooth Muscle Cells

Keisuke Ishizawa; Yuki Izawa-Ishizawa; Sachiyo Ohnishi; Yuki Motobayashi; Kazuyoshi Kawazoe; Shuichi Hamano; Koichiro Tsuchiya; Shuhei Tomita; Kazuo Minakuchi; Toshiaki Tamaki

doi:10.1254/jphs.08236FP

Full Papers

Quercetin Glucuronide Inhibits Cell Migration and Proliferation by Platelet-Derived Growth Factor in Vascular Smooth Muscle Cells

Keisuke Ishizawa, Yuki Izawa-Ishizawa, Sachiyo Ohnishi, Yuki Motobayashi, Kazuyoshi Kawazoe, Shuichi Hamano, Koichiro Tsuchiya, Shuhei Tomita, Kazuo Minakuchi, Toshiaki Tamaki

Author information

Keisuke Ishizawa
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Yuki Izawa-Ishizawa
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Sachiyo Ohnishi
Department of Clinical Pharmacy, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Yuki Motobayashi
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Kazuyoshi Kawazoe
Department of Clinical Pharmacy, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Shuichi Hamano
Department of Pathological Science and Technology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Koichiro Tsuchiya
Department of Medical Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Shuhei Tomita
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Kazuo Minakuchi
Department of Clinical Pharmacy, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan
Toshiaki Tamaki
Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan

Keywords: quercetin glucuronide, platelet-derived growth factor, migration, proliferation, vascular smooth muscle cell

JOURNAL FREE ACCESS

2009 Volume 109 Issue 2 Pages 257-264

DOI https://doi.org/10.1254/jphs.08236FP

View "Advance Publication" version (February 7, 2009).

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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-β-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.

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