Quercetin Abstracts
1. Inhibits LDL oxidation. More potent than Vitamin C and Vitamin E.
Inhibition of mammalian 15-lipoxygenase-dependent lipid peroxidation in low-density lipoprotein by quercetin and quercetin monoglucosides. Luiz da Silva E, Tsushida T, Terao J. National Food Research Institute, Ministry of Agriculture, Forestry, and Fisheries, Ibaraki, Japan. Arch Biochem Biophys. 1998 Jan 15;349(2):313-20.
Lipoxygenase is suggested to be involved in the early event of atherosclerosis by inducing plasma low-density lipoprotein (LDL) oxidation in the subendothelial space of the arterial wall. Since flavonoids such as quercetin are recognized as lipoxygenase inhibitors and they occur mainly in the glycoside form, we assessed the effect of quercetin and its glycosides (quercetin 3-O-beta-glucopyranoside, Q3G; quercetin 4'-O-beta-glucopyranoside, Q4'G; quercetin 7-O-beta-glucopyranoside, Q7G) on rabbit reticulocyte 15-lipoxygenase (15-LOX)-induced human LDL lipid peroxidation and compared it with the inhibition obtained by ascorbic acid and alpha-tocopherol, the main water-soluble and lipid-soluble antioxidants in blood plasma, respectively. Quercetin inhibited the formation of cholesteryl ester hydroperoxides (CE-OOH) and endogenous alpha-tocopherol consumption effectively throughout the incubation period of 6 h. Ascorbic acid exhibited an effective inhibition only in the initial stage and LDL preloaded with fivefold alpha-tocopherol did not affect the formation of CE-OOH compared with the native LDL. CE-OOH formation was inhibited by both quercetin and quercetin monoglucosides in a concentration-dependent manner. Quercetin, Q3G, and Q7G exhibited a higher inhibitory effect than Q4'G (IC50: 0.3-0.5 microM for quercetin, Q3G, and Q7G and 1.2 microM for Q4'G). While endogenous alpha-tocopherol was completely depleted after 2 h of LDL oxidation, quercetin, Q7G, and Q3G prevented the consumption of alpha-tocopherol. Quercetin and its monoglucosides were also exhausted during the LDL oxidation. These results indicate that quercetin glycosides as well as its aglycone are capable of inhibiting lipoxygenase-induced LDL oxidation more efficiently than ascorbic acid and alpha-tocopherol.
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2. May Stop the start of Mammary Tumors and inhibits the growth of Breast Cancer Cells.
1. Miodini P, Fioravanti L, di Fronzo G, Capelletti V. The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. Br J Cancer 1999;80:1150–5.
29. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK. Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada. Nutrition and Cancer (USA) , 1996, 26/2 (167 181)
Two citrus flavonoids, hesperetin and naringenin, found in oranges and grapefruit, respectively, and four noncitrus flavonoids, baicalein, galangin, genistein, and quercetin, were tested singly and in one to one nd growth of a human breast carcinoma cell line, MDA MB 435. The concentration at which cell proliferation was inhibited by 50% (IC50), based on incorporation of (3H)thymidine, varied from 5.9 to 140 microg/ml for the single flavonoids, with the most potent being baicalein. IC50 values for the one to one combinations ranged from 4. 7 microg/ml (quercetin + hespererin, quercetin + naringenin) to 22.5 microg/ml (naringenin + hespererin). All the flavonoids showed low cytotoxicity (>500 microg/ml for 50% cell death). Naringenin is present in grapefruit mainly as its glycosylated form, naringin. These compounds, as well as grapefruit and orange juice concentrates, were tested for their ability to inhibit development of mammary tumors induced by 7,12 dimethylbenz(a)anthracene (DMBA) in female Sprague Dawley rats. Two experiments were conducted in which groups of 21 rats were fed a semipurified diet containing 5% corn oil and were given a 5 mg dose of DMBA intragastrically at approximately 50 days of age while in diestrus. One week later, individual groups were given double strength grapefruit juice or orange juice or fed naringin or naringenin at levels comparable to that provided by the grapefruit juice; in the second experiment, the rats were fed a semipurified diet containing 20% corn oil at that time. As expected, rats fed the high fat diet developed more tumors than rats fed the low fat diet, but in both experiments tumor development was delayed in the groups given orange juice or fed the naringin supplemented diet compared with the other three groups. Although tumor incidence and tumor burden (grams of tumor/rat) were somewhat variable in the different groups, rats given orange juice had a smaller tumor burden than controls, although they grew better than any of the other groups. These experiments provide evidence of anticancer properties of orange juice and indicate that citrus flavonoids are effective inhibitors of human breast cancer cell proliferation in vitro, especially when paired with quercetin, which is widely distributed in other foods.
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3. Quercetin demonstrated inhibition of platelet aggregation which may lessen the threat of athlersclerosis.
25. Zhongguo Yao Li Xue Bao. 1995 May;16(3):223-6. Effects of quercetin on aggregation and intracellular free calcium of platelets. Xiao D, Gu ZL, Bai JP, Wang Z. Department of Pharmacology, Suzhou Medical College, China.
AIM: To study the effects of Que on the intraplatelet free calcium concentration and the effects of calcium on the inhibition of platelet aggregation by Que. METHODS: Using Quin-2 fluorescence technique. RESULTS: Que inhibited the platelet aggregation and the rise of [Ca2+]i induced by thrombin in platelets. The values of IC50 and 95% confidence interval were 146.2 (92.4 - 231.3) and 78.5 (49.5 - 124.4) mumol.L-1, respectively. The inhibitory effects of Que on platelet aggregation induced by thrombin were reduced by adding calcium to the medium, and Que had no effect on thrombin-induced internal Ca2+ release from dense tubular system. CONCLUSION: The inhibitory effects of Que on aggregation and the rise of [Ca2+]i in platelets was mainly due to an inhibition of Ca2+ influx.
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4. Quercetin appears to inhibit oxidation of the lens of the eye and may prevent the formation of cataracts.
22. Free Radic Biol Med. 2002 Jul 1;33(1):63-70. Quercetin metabolism in the lens: role in inhibition of hydrogen peroxide induced cataract. Cornish KM, Williamson G, Sanderson J. School of Biological Sciences, University of East Anglia, Norwich, Norfolk, UK.
Oxidative stress is implicated in the initiation of maturity onset cataract. Quercetin, a major flavonol in the diet, inhibits lens opacification in a lens organ culture oxidative model of cataract. The aim of this research was to investigate the metabolism of quercetin in the lens and show how its metabolism affects the ability to prevent oxidation-induced opacity. The LOCH model (Free Radical Biology & Medicine 26:639; 1999) was employed, using rat lenses to investigate the effects of quercetin and metabolites on hydrogen peroxide-induced opacification. High-performance liquid chromatography analysis showed that the intact rat lens is capable of converting quercetin aglycone to 3'-O-methyl quercetin (isorhamnetin). Over a 6 h culture period no further metabolism of the 3'-O-methyl quercetin occurred. Loss of quercetin in the lens was accounted for by the increase in 3'-O-methyl quercetin. Incubation with 3,5-dinitrocatechol (10 microM), a catechol-O-methyltransferase (COMT) inhibitor, prevented the conversion of quercetin to 3'-O-methyl quercetin. The presence of both membrane-bound and soluble COMT was confirmed by immunoblotting. The results demonstrate that in the rat lens COMT methylates quercetin and that the product accumulates within the lens. Quercetin (10 microM) and 3'-O-methyl quercetin (10 microM) both inhibited hydrogen peroxide- (500 microM) induced sodium and calcium influx and lens opacification. Incubation of lenses with quercetin in the presence of COMT inhibitor revealed that the efficacy of quercetin is not dependent on its metabolism to 3'-O-methyl quercetin. The results indicate dietary quercetin and metabolites are active in inhibiting oxidative damage in the lens and thus could play a role in prevention of cataract formation.
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5. May play a key role in decreasing allergic reactions
19. Clin Exp Allergy. 2000 Apr;30(4):501-8. Effects of luteolin, (found in many plants including soy) quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H. Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
BACKGROUND: Flavonoids have a variety of activities including anti-allergic activities, and are known to inhibit histamine release from human basophils and murine mast cells. OBJECTIVE: The effects of luteolin, a flavone, on the immunoglobulin (Ig) E-mediated allergic mediator release from human cultured mast cells (HCMCs) were investigated and compared with those of baicalein and quercetin. METHODS: HCMCs were sensitized with IgE, and then treated with flavonoids before challenge with antihuman IgE. The amount of released mediators was determined as was mobilization of intracellular Ca2+ concentration, protein kinase C (PKC) translocation and phosphorylation of intracellular proteins were detected after anti-IgE stimulation. RESULTS: Luteolin, baicalein and quercetin inhibited the release of histamine, leukotrienes (LTs), prostaglandin D2 (PGD2), and granulocyte macrophage-colony stimulating factor (GM-CSF) from HCMC in a concentration-dependent manner. Additionally, the three flavonoids inhibited A23187-induced histamine release. As concerns Ca2+ signalling, luteolin and quercetin inhibited Ca2+ influx strongly, although baicalein did slightly. With regard to PKC signalling, luteolin and quercetin inhibited PKC translocation and PKC activity strongly, although baicalein did slightly. The suppression of Ca2+ and PKC signallings might contribute to the inhibition of mediator release. The activation of extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinase (JNK), that were activated just before the release of LTs and PGD2 and GM-CSF mRNA expression in IgE-mediated signal transduction events, were clearly suppressed by luteolin and quercetin. In contrast, the flavonoids did not affect the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway. CONCLUSION: These results indicate that luteolin is a potent inhibitor of human mast cell activation through the inhibition of Ca2+ influx and PKC activation.
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6. Quercetin is protective of the Heart
17. Free Radic Biol Med. 2002 Jun 1;32(11):1220-8. Mitochondrial function in response to cardiac ischemia-reperfusion after oral treatment with quercetin. Brookes PS, Digerness SB, Parks DA, Darley-Usmar V. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-2180, USA. brookes@uab.edu
Polyphenolic compounds present in red wines, such as the flavonol quercetin, are thought capable of cardioprotection through mechanisms not yet clearly defined. It has been established that mitochondria play a critical role in myocardial recovery from ischemia-reperfusion (I-R) damage, and in vitro experiments indicate that quercetin can exert a variety of direct effects on mitochondrial function. The effects of quercetin at concentrations typically found in 1-2 glasses of red wine on cardiac I-R and mitochondrial function in vivo are not known. Quercetin was administered to rats (0.033 mg/kg per day by gavage for 4 d). Isolated Langendorff perfused hearts were subjected to I-R, and cardiac functional parameters determined both before and after I-R. Mitochondria were isolated from post-I-R hearts and their function assessed. Compared to an untreated control group, quercetin treatment significantly decreased the impairment of cardiac function following I-R. This protective effect was associated with improved mitochondrial function after I-R. These results indicate that oral low dose quercetin is cardioprotective, possibly via a mechanism involving protection of mitochondrial function during I-R.
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Helps Prevent Heart disease
Surgery. 2002 Feb;131(2):198-204. Quercetin inhibits human vascular smooth muscle cell proliferation and migration. Alcocer F, Whitley D, Salazar-Gonzalez JF, Jordan WD, Sellers MT, Eckhoff DE, Suzuki K, Macrae C, Bland KI. Department of Surgery, University of Alabama at Birmingham, 35294-0007, USA.
BACKGROUND: The French paradox has been associated with regular intake of red wine, which is enriched with flavonoids. Quercetin, a flavonoid present in the human diet, exerts cardiovascular protection through its antioxidant properties. We hypothesized that the beneficial effect of quercetin also could be related to the inhibition of vascular smooth muscle cell proliferation and migration. METHODS: Human aortic smooth muscle cells (AoSMC) were grown in culture in the presence of serum. Quercetin inhibited the serum-induced proliferation of AoSMC. This inhibition was dose-dependent and not attributed to toxicity. Cell cycle analysis revealed that quercetin arrested AoSMC in the G(0)/G(1) phase. The effect of quercetin on AoSMC migration was examined using explant migration and Transwell migration assays. Quercetin significantly decreased migration in both assays in a consistent manner. Finally, Western blot analysis of AoSMC exposed to quercetin demonstrated a significant reduction in the activation of mitogen-activated protein kinase, a signaling pathway associated with the migration of vascular smooth muscle cells. CONCLUSIONS: Quercetin inhibits the proliferation and migration of AoSMC, concomitant with inhibition of mitogen-activated protein kinase phosphorylation. These findings provide new insights and a rationale for the potential use of quercetin in the prophylaxis of cardiovascular diseases.
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7. Shows strong signs of lowering blood pressure
16. Br J Pharmacol. 2001 May;133(1):117-24. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Duarte J, Perez-Palencia R, Vargas F, Ocete MA, Perez-Vizcaino F, Zarzuelo A, Tamargo J. Department of Pharmacology, School of Pharmacy, University of Granada, 18071 Granada, Spain.
1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. 2. Quercetin induced a significant reduction in systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood pressure. 4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%, P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as compared to WKY rats. However, in quercetin-treated SHR rats both parameters were similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the antioxidant properties of the drug.
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8. Quercetin helped 67% of men with prostatitis in this study.
Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999;54:960–3.