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

Journal of Pharmacological Sciences

Kazuo Minakuchi³  Sachiyo Ohnishi³  Shuhei Tomita¹  Yuki Motobayashi¹  Kazuyoshi Kawazoe³  Toshiaki Tamaki¹  Keisuke Ishizawa¹  Yuki Izawa-Ishizawa¹  Koichiro Tsuchiya⁴  Shuichi Hamano² 

[1] Department of Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan;Department of Pathological Science and Technology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan;Department of Clinical Pharmacy, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan;Department of Medical Pharmacology, The Institute of Health Bioscience, The University of Tokushima Graduate School, Japan

关键词: quercetin glucuronide;    platelet-derived growth factor;    migration;    proliferation;    vascular smooth muscle cell;   

DOI  :  10.1254/jphs.08236FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(40)Cited-By(24)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.

【 授权许可】

Unknown