title: Pharmacology in health food: metabolism of quercetin in vivo and its protective effect against arteriosclerosis.
abstract: Quercetin, a member of the bioflavonoids family, has been proposed to have anti-atherogenic, anti-inflammatory, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. It was recently demonstrated that quercetin 3-O-β-D-glucuronide (Q3GA) is one of the major quercetin conjugates in human plasma, in which the aglycone could not be detected. Although most of the in vitro pharmacological studies have been carried out using only the quercetin aglycone form, experiments using Q3GA would be important to discover the preventive mechanisms of cardiovascular diseases by quercetin in vivo. Therefore we examined the effects of the chemically synthesized Q3GA, as an in vivo form, on vascular smooth muscle cell (VSMC) disorders related to the progression of arteriosclerosis. Platelet-derived growth factor-induced cell migration and proliferation were inhibited by Q3GA in VSMCs. Q3GA attenuated angiotensin II-induced VSMC hypertrophy via its inhibitory effect on JNK and the AP-1 signaling pathway. Q3GA scavenged 1,1-diphenyl-2-picrylhydrazyl radical measured by the electron paramagnetic resonance method. In addition, immunohistochemical studies with monoclonal antibody 14A2 targeting the Q3GA demonstrated that the positive staining specifically accumulates in human atherosclerotic lesions, but not in the normal aorta. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may have preventative effects on arteriosclerosis relevant to VSMC disorders.
authors: Department of Medical Pharmacology, Institute of Health Bioscience, The University of Tokushima Graduate School, Japan. ikeisuke@ph.tokushima-u.ac.jp
authors: Keisuke
authors: K
authors: Ishizawa
authors: Masanori
authors: M
authors: Yoshizumi
authors: Yoshichika
authors: Y
authors: Kawai
authors: Junji
authors: J
authors: Terao
authors: Yoshitaka
authors: Y
authors: Kihira
authors: Yasumasa
authors: Y
authors: Ikeda
authors: Shuhei
authors: S
authors: Tomita
authors: Kazuo
authors: K
authors: Minakuchi
authors: Koichiro
authors: K
authors: Tsuchiya
authors: Toshiaki
authors: T
authors: Tamaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D058870:Food, Organic; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy / Q000188:drug therapy; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D005609:Free Radicals; C443401:quercetin 3-O-glucuronide; D011794:Quercetin