ABSTRACTS QUERCETINA

Adv Exp Med Biol. 2011;701:283-9. doi: 10.1007/978-1-4419-7756-4_38.

Antioxidant properties of quercetin.

Zhang M, Swarts SG, Yin L, Liu C, Tian Y, Cao Y, Swarts M, Yang S, Zhang SB, Zhang K, Ju S, Olek DJ Jr,
Schwartz L, Keng PC, Howell R, Zhang L, Okunieff P.

Source
Department of Radiation Oncology, University of Florida, 2033 Mowry Road, 103633, Gainesville, FL 32610,
USA.

Abstract
Quercetin, a plant-derived aglycone form of flavonoid glycosides, has been used as a nutritional supplement
and may be beneficial against a variety of diseases, including cancer. We examined the antioxidant
properties of quercetin. The reduction potential of quercetin was measured at various pH values using
voltammetric methods, and its total antioxidant capacity (TAC) was measured using the
phosphomolybdenum method. The effect of quercetin on production of reactive oxygen species (ROS) and
nitric oxide (NO) in LPS-stimulated human THP-1 acute monocytic leukemia cells was determined by flow
cytometry using CM-H2DCFDA dye. The results were compared with curcumin, a natural product exhibiting
a similar range of reported health benefits. Results: 1) Quercetin has a higher reduction potential compared
with curcumin at three different pH settings and is comparable to Trolox at pH 7-9.5; 2) its TAC is 3.5 fold
higher than curcumin; 3) it reduced LPS-induced ROS to near normal levels; 4) it reduced LPS-induced NO
production. These data provide a physico-chemical basis for comparing antioxidants, with potential benefits
individually or in combination.
J Pharmacol Sci. 2011;115(4):466-70. Epub 2011 Mar 24.

Pharmacology in health food: metabolism of quercetin in vivo and its

protective effect against arteriosclerosis.
Ishizawa K, Yoshizumi M, Kawai Y, Terao J, Kihira Y, Ikeda Y, Tomita S, Minakuchi K, Tsuchiya K, Tamaki
T.

Source
Department of Medical Pharmacology, Institute of Health Bioscience, The University of Tokushima Graduate
School, Japan. ikeisuke@ph.tokushima-u.ac.jp

Abstract
Quercetin, a member of the bioflavonoids family, has been proposed to have anti-atherogenic, antiinflammatory, and anti-hypertensive properties leading to the beneficial effects against cardiovascular
diseases. It was recently demonstrated that quercetin 3-O--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. Plateletderived 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.
J Pharmacol Sci. 2011;115(4):466-70. Epub 2011 Mar 24.

Pharmacology in health food: metabolism of quercetin in vivo and its

protective effect against arteriosclerosis.
Ishizawa K, Yoshizumi M, Kawai Y, Terao J, Kihira Y, Ikeda Y, Tomita S, Minakuchi K, Tsuchiya K, Tamaki
T.

Source
Department of Medical Pharmacology, Institute of Health Bioscience, The University of Tokushima Graduate
School, Japan. ikeisuke@ph.tokushima-u.ac.jp

Abstract
Quercetin, a member of the bioflavonoids family, has been proposed to have anti-atherogenic, antiinflammatory, and anti-hypertensive properties leading to the beneficial effects against cardiovascular
diseases. It was recently demonstrated that quercetin 3-O--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. Plateletderived 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.

Clin Interv Aging. 2007;2(3):377-87.

Effects of antioxidant supplementation on the aging process.

Fusco D, Colloca G, Lo Monaco MR, Cesari M.

Source
Department of Gerontology, Geriatrics and Physiatry, Catholic University of Sacred Heart, Rome,
Italy.

Abstract
The free radical theory of aging hypothesizes that oxygen-derived free radicals are responsible for
the age-related damage at the cellular and tissue levels. In a normal situation, a balancedequilibrium exists among oxidants, antioxidants and biomolecules. Excess generation of free
radicals may overwhelm natural cellular antioxidant defences leading to oxidation and further
contributing to cellular functional impairment. The identification of free radical reactions as
promoters of the aging process implies that interventions aimed at limiting or inhibiting them
should be able to reduce the rate of formation of aging changes with a consequent reduction of the
aging rate and disease pathogenesis. Even if antioxidant supplementation is receiving growing

attention and is increasingly adopted in Western countries, supporting evidence is still scarce and
equivocal. Major limitations in literature are still needed to be addressed to better evaluate the
potential benefits from antioxidant supplementation: 1) an improved understanding of oxidation
mechanisms possibly at the basis of the aging process, 2) the determination of reliable markers of
oxidative damage and antioxidant status, 3) the identification of a therapeutic window in which an
eventual antioxidant supplementation may be beneficial, 4) a deeper knowledge of the antioxidant
molecules which in several conditions act as pro-oxidants. In the present paper, after a preliminary
introduction to the free radical theory of aging and the rationale of antioxidant supplementation as
an anti-aging intervention, we will present an overview of evidence relating antioxidant
supplementations with clinical conditions typical of older age (ie, cardiovascular disease,
Alzheimer's disease, cancer). We will also discuss studies that have evaluated whether antioxidant
supplementation might improve major outcomes of interest in older persons (ie, physical
performance, muscle strength, longevity). Given the large amount of data available on the
antioxidant supplementation topic, this overview is not intended to be exhaustive. The aim of this
paper is to provide the main basis from which future studies should start and indicate which the
main limitations that need to be addressed are.
Food Chem Toxicol. 1995 Dec;33(12):1061-80.

Review of the biology of Quercetin and related bioflavonoids.

Formica JV, Regelson W.

Source
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University,
Richmond 23298-0678, USA.

Abstract
The French paradox is a dietary anomaly which has focused attention on the Mediterranean diet.
Epidemiological studies revealed that this diet, replete in flavonoid-rich foods (Allium and Brassica
vegetables, and red wine), correlated with the increased longevity and decreased incidence of
cardiovascular disease seen in these populations. The most frequently studied flavonoid, quercetin, has
been shown to have biological properties consistent with its sparing effect on the cardiovascular system.
Quercetin and other flavonoids have been shown to modify eicosanoid biosynthesis (antiprostanoid and antiinflammatory responses), protect low-density lipoprotein from oxidation (prevent atherosclerotic plaque
formation), prevent platelet aggregation (antithrombic effects), and promote relaxation of cardiovascular
smooth muscle (antihypertensive, antiarrhythmic effects). In addition, flavonoids have been shown to have
antiviral and carcinostatic properties. However, flavonoids are poorly absorbed from the gut and are subject
to degradation by intestinal micro-organisms. The amount of quercetin that remains biologically available
may not be of sufficient concentration, theoretically, to explain the beneficial effects seen with the
Mediterranean diet. The role of flavonoids may transcend their presence in food. The activity of flavonoids as
inhibitors of reverse transcriptase suggests a place for these compounds in the control of retrovirus
infections, such as acquired immunodeficiency syndrome (AIDS). In addition to specific effects, the broadmodulating effects of flavonoids as antioxidants, inhibitors of ubiquitous enzymes (ornithine carboxylase,
protein kinase, calmodulin), and promoters of vasodilatation and platelet disaggregation can serve as
starting material for drug development programmes
J Ethnopharmacol. 2012 Sep 28;143(2):383-96. doi: 10.1016/j.jep.2012.07.005. Epub 2012 Jul 20.

Life or death: neuroprotective and anticancer effects of quercetin.

Dajas F.

Source

UNESCO CHAIR Neuroactive natural products, Department of Neurochemistry, Instituto de Investigaciones

Biolgicas Clemente Estable, Montevideo, Uruguay. fjdm@adinet.com.uy

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE:
Quercetin is a ubiquitous flavonoid that is present in numerous plants that are utilized in many different
cultures for their nervous system and anticancer effects. To better understand the neuroprotective and
antiproliferative activities of quercetin, we present a comprehensive review of the divergent actions that
contribute to the ethnopharmacological profile of these plants.
RESULTS:
The pharmacological activities of quercetin that modulate antioxidation/oxidation/kinase-signaling pathways
might be differentially elicited in neurons compared with malignant cells, ultimately promoting cell survival or
death in a cell type- and metabolism-specific manner. Whereas the broad antioxidation and antiinflammatory activities of quercetin are important for neuronal survival, the oxidative, kinase- and cell cycleinhibitory, apoptosis-inducing effects of quercetin are essential for its anticancer effects. The diverse
mechanistic interactions and activities of quercetin that modulate the phosphorylation state of molecules as
well as gene expression would alter the interconnected and concerted intracellular signaling equilibrium,
either inhibiting or strengthening survival signals. These mechanisms, which have been mainly observed in
in vitro studies, cannot be easily translated into an explanation of the divergent simultaneous neuroprotective
and anticancer effects observed in vivo. This is in part due to low bioavailability in plasma and in the brain,
as well as the nature of the actual active molecules.
CONCLUSIONS:
Numerous studies have demonstrated the beneficial effects of chronic quercetin intake, which is
ethnopharmacologically meaningful, as many plants that are chronically ingested by people contain
quercetin. Although quercetin and quercetin-containing plants exhibit potential as therapeutic modalities in
neuropathology and in cancer, the data collectively highlight the need to elucidate issues such as
bioavailability as well as its correlation with effectiveness at biomarkers in vivo. There would be an increased
potentential of these plants for chemoprevention and neuropathology prevention.
Food Chem Toxicol. 1995 Dec;33(12):1061-80.

Review of the biology of Quercetin and related bioflavonoids.

Formica JV, Regelson W.

Source
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University,
Richmond 23298-0678, USA.

Abstract
The French paradox is a dietary anomaly which has focused attention on the Mediterranean diet.
Epidemiological studies revealed that this diet, replete in flavonoid-rich foods (Allium and Brassica
vegetables, and red wine), correlated with the increased longevity and decreased incidence of
cardiovascular disease seen in these populations. The most frequently studied flavonoid, quercetin, has
been shown to have biological properties consistent with its sparing effect on the cardiovascular system.
Quercetin and other flavonoids have been shown to modify eicosanoid biosynthesis (antiprostanoid and antiinflammatory responses), protect low-density lipoprotein from oxidation (prevent atherosclerotic plaque
formation), prevent platelet aggregation (antithrombic effects), and promote relaxation of cardiovascular
smooth muscle (antihypertensive, antiarrhythmic effects). In addition, flavonoids have been shown to have
antiviral and carcinostatic properties. However, flavonoids are poorly absorbed from the gut and are subject
to degradation by intestinal micro-organisms. The amount of quercetin that remains biologically available

may not be of sufficient concentration, theoretically, to explain the beneficial effects seen with the
Mediterranean diet. The role of flavonoids may transcend their presence in food. The activity of flavonoids as
inhibitors of reverse transcriptase suggests a place for these compounds in the control of retrovirus
infections, such as acquired immunodeficiency syndrome (AIDS). In addition to specific effects, the broadmodulating effects of flavonoids as antioxidants, inhibitors of ubiquitous enzymes (ornithine carboxylase,
protein kinase, calmodulin), and promoters of vasodilatation and platelet disaggregation can serve as
starting material for drug development programmes.
Arch Toxicol Suppl. 1998;20:237-48.

Bioavailability and health effects of dietary flavonols in man.

Hollman PC, Katan MB.

Source
DLO State Institute for Quality Control of Agricultural Products (RIKILT-DLO), Wageningen, The
Netherlands.

Abstract
Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Over 4000 different
flavonoids have been described, and they are categorized into flavonols, flavones, catechins, flavanones,
anthocyanidins, and isoflavonoids. Flavonoids have a variety of biological effects in numerous mammalian
cell systems, as well as in vivo. Recently much attention has been paid to their antioxidant properties and to
their inhibitory role in various stages of tumour development in animal studies. Quercetin, the major
representative of the flavonol subclass, is a strong antioxidant, and prevents oxidation of low density
lipoproteins in vitro. Oxidized low density lipoproteins are atherogenic, and are considered to be a crucial
intermediate in the formation of atherosclerotic plaques. This agrees with observations in epidemiological
studies that the intake of flavonols and flavones was inversely associated with subsequent coronary heart
disease. However, no effects of flavonols on cancer were found in these studies. The extent of absorption of
flavonoids is an important unsolved problem in judging their many alleged health effects. Flavonoids present
in foods were considered non-absorbable because they are bound to sugars as beta-glycosides. Only free
flavonoids without a sugar molecule, the so-called aglycones were thought to be able to pass through the gut
wall. Hydrolysis only occurs in the colon by microorganisms, which at the same time degrade flavonoids. We
performed a study to quantify absorption of various dietary forms of quercetin. To our surprise, the quercetin
glycosides from onions were absorbed far better than the pure aglycone. Subsequent pharmacokinetic
studies with dietary quercetin glycosides showed marked differences in absorption rate and bioavailability.
Absorbed quercetin was eliminated only slowly from the blood. The metabolism of flavonoids has been
studied frequently in various animals, but very few data in humans are available. Two major sites of flavonoid
metabolism are the liver and the colonic flora. There is evidence for O-methylation, sulfation and
glucuronidation of hydroxyl groups in the liver. Bacterial ring fission of flavonoids occurs in the colon. The
subsequent degradation products, phenolic acids, can be absorbed and are found in urine of animals.
Quantitative data on metabolism are scarce
Recenti Prog Med. 2004 Jul-Aug;95(7-8):345-51.

[Flavonoids: risks or therapeutic opportunities?].

[Article in Italian]
Firenzuoli F, Gori L, Crupi A, Neri D.

Source
Centro di Medicina Naturale, Ospedale S. Giuseppe, Azienda USL 11, Empoli. f.firenzuoli@usl11.toscana.it

Abstract

Flavonoids are polyphenolic compounds that occur ubiquitously in fruits and vegetables. Over 4,000 different
flavonoids have been described, and they are categorized into flavonols, flavones, catechins, flavanones,
anthocyanidins and isoflavonoids. Flavonoids have many different biological effects in numerous mammalian
cell systems, showed both in vitro and in vivo. Recently, much attention has been paid to their antioxidant
properties and to their inhibitory role in various stages of tumour development in animal studies. In
epidemiological studies the intake of flavonoids was inversely associated with subsequent coronary heart
disease and cancer. Soy, St. John's Wort, Silybum marianum, Ginkgo biloba, Citrus species, Vaccinum
mirtillus, Hawthorn and tea are medicinal plants containing flavonoids whose efficacy in the treatment of a
variety of diseases has been demonstrated in numerous clinical studies. The main question that has not
been answered satisfactorily deal with the triad absorption/metabolism/efficacy of flavonoids and is actually
an important unsolved problem in judging their many alleged health effects. The aim of this review is based
on providing by means of experimental and clinical studies information about efficacy and toxicity of
flavonoids, especially focusing on infantile leukaemia for which there has been an international warning
without sufficient and affordable scientific data.