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Quercetin, Inflammation and Immunity

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In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
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nutrients
Review
Quercetin, Inflammation and Immunity
Yao Li 1,*, Jiaying Yao 1, Chunyan Han 1, Jiaxin Yang 1, Maria Tabassum Chaudhry 1,
Shengnan Wang 1, Hongnan Liu 2,* and Yulong Yin 2, *
1Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China;
qiumengyouzhi@163.com (J.Y.); hanchunyan920317@163.com (C.H.); jiaxinyang8040@163.com (J.Y.);
mariach046@yahoo.com (M.T.C.); 13674620839@163.com (S.W.)
2
Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central China,
Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy, Livestock,
Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical, Agriculture,
Chinese Academy of Sciences, Changsha 410125, China
*Correspondence: liyao@neau.edu.cn (Y.L.); liuhn@isa.ac.cn (H.L.); yinyulong@isa.ac.cn (Y.Y.);
Tel.: +86-147-4515-6908 (Y.L.); +86-731-8461-9767 (H.L. & Y.Y.)
Received: 25 January 2016; Accepted: 9 March 2016; Published: 15 March 2016
Abstract: In vitro
and some animal models have shown that quercetin, a polyphenol derived from
plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and
antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary
permeability. This review focuses on the physicochemical properties, dietary sources, absorption,
bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation
and immune function. According to the results obtained both
in vitro
and
in vivo
, good perspectives
have been opened for quercetin. Nevertheless, further studies are needed to better characterize the
mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
Keywords: quercetin; inflammation; immune function; dietary sources; metabolism
1. Introduction
Quercetin, a flavonoid found in fruits and vegetables, has unique biological properties that
may improve mental/physical performance and reduce infection risk [
1
]. These properties form
the basis for potential benefits to overall health and disease resistance, including anti-carcinogenic,
anti-inflammatory, antiviral, antioxidant, and psychostimulant activities, as well as the ability to inhibit
lipid peroxidation, platelet aggregation and capillary permeability, and to stimulate mitochondrial
biogenesis [
2
]. Therefore, there is a pressing need for well-designed clinical trials to evaluate this novel
dietary supplement further. This article reviews effects of quercetin on inflammation and immunity in
mental and physical performance and health.
2. Physicochemical Properties of Quercetin
Quercetin is categorized as a flavonol, one of the six subclasses of flavonoid compounds. The name
has been used since 1857, and is derived from quercetum (oak forest), after Quercus. It is a naturally
occurring polar auxin transport inhibitor [
3
]. The International Union of Pure and Applied Chemistry
(IUPAC) nomenclature for quercetin is 3, 3
1
, 4
1
, 5, 7-pentahydroxyflvanone (or its synonym 3, 3
1
, 4
1
, 5,
7-pentahydroxy-2-phenylchromen-4-one). This means that quercetin has an OH group attached at
positions 3, 5, 7, 31, and 41. Common forms of quercetin were shown in Figure 1.
Nutrients 2016,8, 167; doi:10.3390/nu8030167 www.mdpi.com/journal/nutrients
Nutrients 2016,8, 167 2 of 14
Nutrients2016,8,1672of13
Figure1.Molecularstructureofquercetin,quercetinglycoside,quercetinglucuronide,quercetin
sulfateandmethylatedquercetin.
Quercetin(C15H10O7)isanaglycone,lackinganattachedsugar.Itisabrilliantcitronyellow
needlecrystalandentirelyinsolubleincoldwater,poorlysolubleinhotwater,butquitesolublein
alcoholandlipids.Aquercetinglycosideisformedbyattachingaglycosylgroup(asugarsuchas
glucose,rhamnose,orrutinose)asareplacementforoneoftheOHgroups(commonlyatposition3).
Theattachedglycosylgroupcanchangethesolubility,absorption,andinvivoeffects.Asageneral
ruleofthumb,thepresenceofaglycosylgroup(quercetinglycoside)resultsinincreasedwater
solubilitycomparedtoquercetinaglycone[4,5].
Aquercetinglycosideisuniquebytheattachedglycosylgroup.Generally,thetermquercetin
shouldbeusedtodescribetheaglyconeonly;however,thenameisoccasionallyusedtoreferto
quercetintypemolecules,includingitsglycosidesinresearchandthesupplementindustry.
3.DietarySourcesofQuercetin
Quercetintypeflavonols(primarilyasquercetinglycosides),themostabundantofthe
flavonoidmolecules,arewidelydistributedinplants.Theyarefoundinavarietyoffoodsincluding
apples,berries,Brassicavegetables,capers,grapes,onions,shallots,tea,andtomatoes,aswellas
manyseeds,nuts,flowers,barks,andleaves.Quercetinisalsofoundinmedicinalbotanicals,
includingGinkgobiloba,Hypericumperforatum,andSambucuscanadensis[6–8].Inredonions,higher
concentrationsofquercetinoccurintheoutermostringsandinthepartclosesttotheroot,thelatter
beingthepartoftheplantwiththehighestconcentration[9].Onestudyfoundthatorganically
growntomatoeshad79%morequercetinthanchemicallygrownfruit[10].Quercetinispresentin
variouskindsofhoneyfromdifferentplantsources[11].Foodbasedsourcesofquercetininclude
vegetables,fruits,berries,nuts,beveragesandotherproductsofplantorigin[12].Inthedetermined
food,thehighestconcentrationis234mg/100gofedibleportionincapers(raw),thelowest
concentrationis2mg/100gofedibleportioninblackorgreentea(Camelliasinensis)[13].
Dietaryintakeofquercetinwasdifferentinseveralcountries.Theestimatedflavonoidintake
rangesfrom50to800mg/day(quercetinaccountsfor75%),mostlydependingontheconsumption
offruitsandvegetablesandtheintakeoftea[14].IntheSuihuaareaofnorthernChina,quercetin
intakewasreportedtobe4.37mg/day,wherethemainfoodsourcesofflavonolwasapples(7.4%),
Figure 1.
Molecular structure of quercetin, quercetin glycoside, quercetin glucuronide, quercetin sulfate
and methylated quercetin.
Quercetin (C15H10O7) is an aglycone, lacking an attached sugar. It is a brilliant citron yellow
needle crystal and entirely insoluble in cold water, poorly soluble in hot water, but quite soluble in
alcohol and lipids. A quercetin glycoside is formed by attaching a glycosyl group (a sugar such as
glucose, rhamnose, or rutinose) as a replacement for one of the OH groups (commonly at position 3).
The attached glycosyl group can change the solubility, absorption, and
in vivo
effects. As a general rule
of thumb, the presence of a glycosyl group (quercetin glycoside) results in increased water solubility
compared to quercetin aglycone [4,5].
A quercetin glycoside is unique by the attached glycosyl group. Generally, the term quercetin
should be used to describe the aglycone only; however, the name is occasionally used to refer to
quercetin-type molecules, including its glycosides in research and the supplement industry.
3. Dietary Sources of Quercetin
Quercetin-type flavonols (primarily as quercetin glycosides), the most abundant of the flavonoid
molecules, are widely distributed in plants. They are found in a variety of foods including apples,
berries, Brassica vegetables, capers, grapes, onions, shallots, tea, and tomatoes, as well as many
seeds, nuts, flowers, barks, and leaves. Quercetin is also found in medicinal botanicals, including
Ginkgo biloba,Hypericum perforatum, and Sambucus canadensis [
6
8
]. In red onions, higher concentrations
of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part
of the plant with the highest concentration [
9
]. One study found that organically grown tomatoes
had 79% more quercetin than chemically grown fruit [
10
]. Quercetin is present in various kinds of
honey from different plant sources [
11
]. Food-based sources of quercetin include vegetables, fruits,
berries, nuts, beverages and other products of plant origin [
12
]. In the determined food, the highest
concentration is 234 mg/100 g of edible portion in capers (raw), the lowest concentration is
2 mg/100 g
of edible portion in black or green tea (Camellia sinensis) [13].
Dietary intake of quercetin was different in several countries. The estimated flavonoid intake
ranges from 50 to 800 mg/day (quercetin accounts for 75%), mostly depending on the consumption of
Nutrients 2016,8, 167 3 of 14
fruits and vegetables and the intake of tea [
14
]. In the Suihua area of northern China, quercetin intake
was reported to be 4.37 mg/day, where the main food sources of flavonol was apples (7.4%), followed
by potatoes (3.9%), lettuce (3.8%) and oranges (3.8%) [
15
], whereas the average quercetin intake was
4.43 mg/day, with apple (3.7%), potato (2.5%), celery (2.2%), eggplant (2.2%), and actinidia (1.6%) being
the main food sources of quercetin in Harbin, China [
16
]. The most recent study showed that quercetin
intake is about 18 mg/day for Chinese healthy young males. In the USA, flavonol intake is about
13 mg/day for U.S. adults, while quercetin represents three-quarters of this amount. The mean quercetin
intake was approximately 14.90 to 16.39 mg per day. Onions, tea, and apples contained high amounts
of quercetin [
17
]. In Japan, the average and median quercetin intakes were 16.2 and 15.5 mg/day,
respectively; the quercetin intake by men was lower than that by women; and the quercetin intakes
showed a low correlation with age in both men and women. The estimated quercetin intake was similar
during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer
and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good
sources of quercetin in summer [18]. In Australia, black and green teas were the dominant sources of
quercetin. Other sources included onion, broccoli, apple, grape, and beans [
19
]. Analysis of the 24-h
recall data indicated an average adult intake of total flavonoids (>18 years) of 454 mg/day. Apple was
the most important source of quercetin until age 16–18 years, after which onion became an increasingly
important prominent source [
19
]. In Spain, the average daily intake of quercetin is 18.48 mg/day, which
is significantly higher than that in the United States (9.75 mg/day), based on sources like tea, citrus
fruits and juice, beers and ales, wines, melon, apples, onions, berries and bananas [20].
4. Absorption, Bioavailability and Metabolism of Quercetin
The first investigation on the pharmacokinetics of quercetin in humans suggested very poor oral
bioavailability after a single oral dose (~2%). The estimated absorption of quercetin glucoside, the
naturally occurring form of quercetin, ranges from 3% to 17% in healthy individuals receiving 100 mg.
The relatively low bioavailability of quercetin may be attributed to its low absorption, extensive
metabolism and/or rapid elimination.
4.1. Absorption
Quercetin glycosides might be differently absorbed based on the type of sugar attached [
21
].
Available evidence indicates that quercetin glucosides (like those found predominantly in onion
or shallot flesh) are far better absorbed than its rutinosides (the major quercetin glycoside in tea).
The glucosides are efficiently hydrolyzed in the small intestine by beta-glucosidases to the aglycone
form, much of which is then absorbed [
22
]. Quercetin glucuronic acid and its sulfuric acid derivatives
were more easily absorbed than quercetin [
22
]. Thereafter, its absorption is affected by differences in
its glycosylation, the food matrix from which it is consumed, and the co-administration of dietary
components such as fiber and fat [
23
]. Thus different sugar types and sugar group conjugation sites
will result in absorption variation.
Quercetin and derivatives are stable in gastric acid; however, there were no reports whether they
can be absorbed in stomach. Studies suggest that quercetin is absorbed in the upper segment of small
intestinal [24,25].
Among quercetin’s derivatives, conjugated forms of its glycosides are better absorbed than quercetin.
Purified quercetin glucosides are capable of interacting with the sodium dependent glucose transport
receptors in the mucosal epithelium and may therefore be absorbed by the small intestine in vivo [21].
4.2. Transformation and Transportation
After absorption, quercetin becomes metabolized in various organs including the small intestine,
colon, liver and kidney. Metabolites formed in the small intestine and liver by biotransformation
enzymes include the methylated, sulfo-substituted and glucuronidated forms [
26
,
27
]. A study
Nutrients 2016,8, 167 4 of 14
regarding the tissue distribution in rats and pigs has shown that the highest accumulation of quercetin
and its metabolites are found in (rat) lung and (pig) liver and kidney [28].
Quercetin and derivatives are transformed into various metabolites (phenolic acid) by enteric
bacteria and enzymes in intestinal mucosal epithelial cells. These metabolites are absorbed, transformed
or excreted later. Moreover, bacteria ring fission of the aglycon occurs in both the small intestine and
colon, resulting in the breakdown of the backbone structure of quercetin and the subsequent formation
of smaller phenolics [29].
Quercetin metabolites analyzed in plasma and liver samples have shown that the concentrations
of its derivatives in the liver were lower than those in plasma, and the hepatic metabolites were
intensively methylated (90%–95%) [
30
]. Limited studies suggest that quercetin was methylated,
vulcanized and glucuronidated in liver [31].
Continuous intake of diet containing quercetin accumulated in blood and significantly increased
quercetin concentration in plasma, which was significantly correlated to its dietary content [
32
]. Quercetin is
present in a conjugated form in human blood whose major form is glycoside [
33
]. While isorhamnetin
and glucoside acid-sulfated derivatives of quercetin account for 91.5% of its metabolites, other
metabolites include its glucuronoside and methylated form [
34
]. Boulton also found that quercetin
conjugated plasma protein (albumin account for 99.4%), thus decreased its bioavailability in cells [
35
].
4.3. Excretion
The limited research suggests that quercetin and its metabolites tend to accumulate in the organs
involved in its metabolism and excretion, and that perhaps mitochondria might be an area of quercetin
concentration within cells [
36
42
]. Kidney is a major organ of excretion. Quercetin concentration in
urine increased with the increasing dose and time after intake of fruit juice was ingested in human [
36
],
perhaps benzoic acid derivatives are common metabolite of quercetin [
37
]. Human subjects can
absorb significant amounts of quercetin from food or supplements, and elimination is quite slow, with
a reported half-life ranging from 11 to 28 h [
38
]. The average terminal half-life of quercetin is 3.5 h [
39
].
The total recovery of C-quercetin in urine, feces and exhaled air is highly variable, depending on
the individual [
40
]. A high amount of absorbed quercetin is extensively metabolized and eventually
eliminated by the lungs [
41
]. Additional literature suggests that isoquercetin (glycosylated quercetin)
is more completely absorbed than quercetin in the aglycone form, and that the simultaneous ingestion
of quercetin with vitamin C, folate and additional flavonoids improves bioavailability [38,42].
All of these studies indicate that quercetin glucosides is absorbed in the upper segment of small
intestinal, then is methylated, sulfo-substituted and glucuronidated by biotransformation enzymes in
the small intestine and liver, and is finally excreted by kidney in urine.
5. Effect of Quercetin on Inflammation and Immune Function
5.1. In Vitro
5.1.1. Anti-Inflammation and Promotion of Immunity
Quercetin was reported as a long lasting anti-inflammatory substance that possesses strong
anti-inflammatory capacities [
43
,
44
]. It possesses anti-inflammatory potential that can be expressed
on different cell types, both in animal and human models [
45
53
]. It is known to possess both
mast cell stabilizing and gastrointestinal cytoprotective activity [
54
]. It can also play a modulating,
biphasic and regulatory action on inflammation and immunity [
53
]. Additionally, quercetin has
an immunosuppressive effect on dendritic cells function [55].
5.1.2. Mechanism of Action
Several studies
in vitro
using different cell lines have shown that quercetin inhibits
lipopolysaccharide (LPS)-induced tumor necrosis factor
α
(TNF-
α
) production in macrophages [
45
]
Nutrients 2016,8, 167 5 of 14
and LPS-induced IL-8 production in lung A549 cells [
46
]. Moreover, in glial cells it was even
shown that quercetin can inhibit LPS-induced mRNA levels of TNF-
α
and interleukin (IL)-1
α
, this
effect of quercetin resulted in a diminished apoptotic neuronal cell death induced by microglial
activation [
47
]. Quercetin inhibits production of inflammation-producing enzymes (cyclooxygenase
(COX) and lipoxygenase (LOX)) [
48
,
49
]. It limits LPS-induced inflammation via inhibition of
Src- and Syk-mediated phosphatidylinositol-3-Kinase (PI3K)-(p85) tyrosine phosphorylation and
subsequent Toll Like Receptor 4 (TLR4)/MyD88/PI3K complex formation that limits activation of
downstream signaling pathways in RAW 264.7 cells [
50
]. It can also inhibit Fc
ε
RI-mediated release
of pro-inflammatory cytokines, tryptase and histamine from human umbilical cord blood-derived
cultured mast cells (hCBMCs); this inhibition appears to involve in inhibition of calcium influx, as well
as phospho-protein kinase C (PKC) [51]. The study of quercetin against H2O2-induced inflammation
showed the protective effects of quercetin against inflammation in human umbilical vein endothelial
cells (HUVECs) and indicated that the effect was mediated via the downregulation of vascular cell
adhesion molecule 1 (VCAM-1) and CD80 expression [52].
Quercetin significantly induces the gene expression as well as the production of Th-1 derived
interferon-
γ
(IFN-
γ
) and down-regulates Th-2 derived interleukin 4 (IL-4) by normal peripheral blood
mononuclear cells (PBMC). Furthermore, quercetin treatment increased the phenotypic expression of
IFN-
γ
cells and decreased IL-4 positive cells by flow cytometry analysis, which corroborate with protein
secretion and gene expression studies. These results suggest that the beneficial immuno-stimulatory
effects of quercetin may be mediated through the induction of Th-1 derived cytokine, IFN-
γ
, and
inhibition of Th-2 derived cytokine, IL-4 [56].
Quercetin is able to inhibit matrix metalloproteinases, which are normally inhibited by plasminogen
activator inhibitor 1 (PAI-1) in human dermal fibroblasts [
57
]. IL-1-stimulated IL-6 production from
human mast cells is regulated by biochemical pathways distinct from IgE-induced degranulation, and
quercetin can block both IL-6 secretion and two key signal transduction steps involved [58].
Quercetin is known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity.
A study demonstrates that quercetin has a direct regulatory effect on basic functional properties of immune
cells which may be mediated by the extracellular regulated kinase 2 (Erk2) mitogen-activated protein
(MAP) kinase signal pathway in human mitogen-activated PBMC and purified T lymphocytes [54].
The property proves inhibitory to a huge panoply of molecular targets in the micromolar concentration
range, either by down-regulating or suppressing many inflammatory pathways and functions.
Quercetin has shown a biphasic behavior in basophils at nanomolar doses and hence its action
on cells involved in allergic inflammation. Quercetin affects immunity and inflammation by acting
mainly on leukocytes and targeting many intracellular signaling kinases and phosphatases, enzymes
and membrane proteins are often crucial for a cellular specific function. However, the wide group
of intracellular targets and the elevated number of natural compounds potentially effective as
anti-inflammatory therapeutic agents, asks for further insights and evidence to comprehend the
role of these substances in animal cell biology [53].
In vitro
treatment of activated T cells with quercetin blocks IL-12-induced tyrosine phosphorylation
of JAK2, TYK2, STAT3, and STAT4, resulting in a decrease in IL-12-induced T cell proliferation and Th1
differentiation [59].
Taken as
in vitro
together, the possible pathway of quercetin on inflammation and immune
function is as follows (Figure 2).
Nutrients 2016,8, 167 6 of 14
Nutrients2016,8,1676of13
Figure2.Workingmodelonhowquercetinblocktumornecrosisfactor‐α (TNFα)mediated
inflammation.QuercetinpreventsTNF‐αfromdirectlyactivatingextracellularsignalrelatedkinase
(ERK),cJunNH2terminalkinase(JNK),cJun,andnuclearfactor‐κB(NF‐κB),whicharepotent
inducersofinflammatorygeneexpressionandproteinsecretion.Inaddition,quercetinmay
indirectlypreventinflammationbyincreasingperoxisomeproliferatoractivatedreceptorc(PPARγ)
activity,therebyantagonizingNF‐κBoractivatorprotein1(AP1)transcriptionalactivationof
inflammatorygenes.Together,theseblockTNF‐α‐mediatedinductionofinflammatorycascades.
Themainactionofquercetinoninflammationandimmunefunctioninvitroissummarizedin
theTable1.
Table1.Summaryofthemaineffectsofquercetinoninflammationandimmunefunctioninvitro.
DosageCellLinesEffect Mechanism Reference
Cellsfromanimals
100μmol/LPulmonaryEpithelial
Cell(A549)
Antiinflammation
PARP1inhibitionandpreservationof
cellularNAD1andenergyproduction[46]
100μmol/LN9microglialcells
InhibitionofTNFαandIL1α;Reduce
ofapoptoticneuronalcelldeath
inducedbymicroglialactivation
[47]
3μmol/LGuneapigepithelial
cells
Inhibitionofbothcyclooxygenaseand
lipoxygenase[48]
15–30μmol/LRatliverepithelial
(RLE)cells
InhibitionofarseniteinducedCOX2
expressionmainlybyblockingthe
activationofthePI3Ksignaling
pathway
[49]
‐ RAW264.7cells
InhibitionofSrc‐andSykmediated
PI3K(p85)tyrosinephosphorylation
andsubsequentTLR4/MyD88/PI3K
complexformationthatlimits
activationofdownstreamsignaling
pathways
[50]
Cellsfromhuman
10μmol/L
Humanumbilicalcord
bloodderivedcultured
mastcells(hCBMCs)
Antiallergicand
antiinflammation;
Protectiveeffects
againstcellinjury;
Gastrointestinal
cytoprotectiveaction
Inhibitionofintracellularcalcium
influxandPKCthetasignaling[51]
50or100μgTlymphocyteBlockageofinterleukin12signaling
throughJAKSTATpathway[52]
‐ Mastcell
Stabilizationofmastcelland
gastrointestinalcytoprotectionvia
lactonestimulatingmucusproduction,
andinhibitinghistamineand
serotoninreleasefromintestinalmast
cells
12.5–25.0
mmol/L
Human
inflamed/UVirradiated
skin
InhibitionofMMP1and
downregulationofMMP1expression
viaaninhibitionoftheAP1activation
[54]
Figure 2.
Working model on how quercetin block tumor necrosis factor-
α
(TNF
α
)-mediated inflammation.
Quercetin prevents TNF-
α
from directly activating extracellular signal-related kinase (ERK), c-Jun
NH
2
-terminal kinase (JNK), c-Jun, and nuclear factor-
κ
B (NF-
κ
B), which are potent inducers of
inflammatory gene expression and protein secretion. In addition, quercetin may indirectly prevent
inflammation by increasing peroxisome proliferator-activated receptor c (PPAR
γ
) activity, thereby
antagonizing NF-
κ
B or activator protein-1(AP-1) transcriptional activation of inflammatory genes.
Together, these block TNF-α-mediated induction of inflammatory cascades.
The main action of quercetin on inflammation and immune function
in vitro
is summarized in the
Table 1.
Table 1. Summary of the main effects of quercetin on inflammation and immune function in vitro.
Dosage Cell Lines Effect Mechanism Reference
Cells from animals
100 µmol/L Pulmonary Epithelial
Cell (A549)
Anti-inflammation
PARP-1 inhibition and preservation of
cellular NAD1 and energy production
[46]
100 µmol/L N9 microglial cells
Inhibition of TNF
α
and IL-1
α
; Reduce
of apoptotic neuronal cell death
induced by microglial activation
[47]
3µmol/L
Gunea pig epithelial cells
Inhibition of both cyclooxygenase
and lipoxygenase [48]
15–30 µmol/L Rat liver epithelial (RLE)
cells
Inhibition of arsenite-induced
COX-2 expression mainly by blocking
the activation of the PI3K
signaling pathway
[49]
- RAW 264.7 cells
Inhibition of Src- and Syk-mediated
PI3K-(p85) tyrosine phosphorylation
and subsequent TLR4/MyD88/PI3K
complex formation that
limits activation of downstream
signaling pathways
[50]
Cells from human
10 µmol/L
Human umbilical cord
blood-derived cultured
mast cells (hCBMCs)
Anti-allergic and
anti-inflammation;
Protective effects
against cell injury;
Gastrointestinal
cytoprotective action
Inhibition of intracellular calcium
influx and PKC theta signaling [51]
50 or 100 µg T lymphocyte Blockage of interleukin-12 signaling
through JAK-STAT pathway [52]
- Mast cell
Stabilization of mast cell and
gastrointestinal cytoprotection via
lactone stimulating mucus
production, and inhibiting histamine
and serotonin release from intestinal
mast cells
Nutrients 2016,8, 167 7 of 14
Table 1. Cont.
Dosage Cell Lines Effect Mechanism Reference
12.5–25.0 mmol/L
Human
inflamed/UV-irradiated
skin
Inhibition of MMP-1 and
down-regulation of MMP-1
expression via an inhibition of the
AP-1 activation
[54]
0–210 µmol/L
Human umbilical
vein endothelial
cells (HUVECs)
Downregulation of VCAM-1 and
CD80 expression [56]
0.5–50 mmol/L
Human normal
peripheral blood
mononuclear cells
Beneficial
immuno-stimulatory
effects
Induction of Th-1 derived cytokine,
IFNgamma, and inhibition of Th-2
derived cytokine, IL-4
[57]
1–100 mmol/L
Human umbilical cord
blood-derived cultured
mast cells (hCBMCs)
Inhibition of IL-1-induced
IL-6 secretion, p38 and
PKC-theta phosphorylation
[58]
ě100 mmol/L or
ď50 mmol/L
Mouse endritic
cells (mDCs) Immunosuppression
Inhibition of DC activation; DC
apoptosis; Downregulation of the
cytokines and chemokines,
disturbance of immunoregulation;
Attenuation of LPS-induced DC
maturation and limitation of
immunostimulatory activity;
downregulate of endocytosis and
impairment of Ag loading;
suppression of DC migration and
disconnection of the induction of
adaptive immune responses
[55]
5.2. In Vivo
5.2.1. Animal Models
Quercetin exerts inflammation and immune modulating activity in several murine models of
autoimmunity.
In vivo
, animal experiments also support an anti-inflammatory effect. Quercetin ameliorates
the inflammatory response induced by carrageenan [
60
] and a high-fat diet [
61
]. Quercetin reduced
visceral adipose tissue TNF-
α
and nitric oxide production and downregulated nitric oxide synthase
(NOS) expression in obese Zucker rats [
62
]. In chronic rat adjuvant induced arthritis, quercetin
decreased clinical signs of arthritis compared to untreated controls [63].
In rats, post-trauma administration of quercetin improves recovery of motor function after acute
traumatic spinal cord injury. Intraperitoneal (IP) doses of 5–100 micromoles quercetin/kg body weight
resulted in half or more of the animals walking, although with deficit [
64
]. This ability to promote
recovery from spinal cord injury appears to be highly dependent on the dose and frequency of dosing.
In this study a lower IP dose was ineffective. In another study, compared to an untreated control
group of animals (none of which recovered motor function sufficient to walk), quercetin administration
twice daily for three or 10 days resulted in about 50 percent of the animals recovering sufficient motor
function to walk. However, when quercetin was injected three times daily, none of the nine animals
recovered the ability to walk [65].
5.2.2. Mechanism of Action in Animal
Study has shown that quercetin exerted protective effect against irradiation-induced inflammation in
mice through increasing cytokine secretion [
66
]. Quercetin possesses activity against isoproterenol-induced
myocardial oxidative injury and immunity function impairment, and that the mechanism of
pharmacological action was related at least in part to the antioxidant activity of quercetin [
67
].
Quercetin decreased histological signs of acute inflammation in the treated animals in a dose-dependent
manner via suppressing leucocyte recruitment, decreasing chemokine levels and levels of the
lipid peroxidation end-product malondialdehyde, and increasing antioxidant enzyme activity in
experimental rat model [68].
Nutrients 2016,8, 167 8 of 14
Quercetin ameliorated experimental allergic encephalomyelitis (EAE) by blocking IL-12 signaling
and Th1 differentiation [
58
] and experimental autoimmune myocarditis (EAM) in Dark Agouti rats
by interfering with production of pro-inflammatory (TNF-
α
and IL-17) and/or anti-inflammatory
(IL-10) cytokines [
69
]. Quercetin most likely universally suppresses the accumulation and activation
of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression
associated with mitochondrial oxidative phosphorylation in Western diet-induced obese mice.
Suppression of oxidative stress and NF-
κ
B activity likely contributed to the prevention of the
accumulation and activation of immune cells and resulting chronic inflammation of epididymal
adipose tissue in Western diet-induced obese mice [70].
5.2.3. Clinical Studies
Diet supplementation with combinations of resveratrol, pterostilbene, morin hydrate, quercetin,
δ
-tocotrienol, riboflavin, and nicotinic acid reduces cardiovascular risk factors in humans when
used as nutritional supplements with, or without, other dietary changes in healthy seniors and
hypercholesterolemic subjects [71].
In a randomized, double-blinded, placebo-controlled trial, 1002 subjects took 500 or 1000 mg/day
quercetin or a placebo for 12 weeks. For the group as a whole, quercetin supplementation had
no significant influence on rates of upper respiratory tract infections (URTI) compared to placebo.
In a subgroup of subjects age 40 or older who self-rated themselves as physically fit, 1000 mg/day
quercetin resulted in a statistically significant reduction in total sick days and symptom severity
associated with URTI [
72
]. Female subjects were supplemented with 500 or 1000 mg/day quercetin
or placebo for 12 weeks. While quercetin supplementation significantly increased plasma quercetin
levels, it had no influence on measure of immune function [
73
]. Quercetin (100 mg/day) did not alter
exercise-induced changes in several measures of immune function following three days of intense
exercise in trained athletes, but it significantly reduced URTI incidence (1 of 20 subjects in active versus
9 of 20 in placebo group) during the two-week post-exercise period [
74
]. A similar lack of effect on
strenuous exercise-induced immune system perturbation was found in subjects who took 1000 mg/day
of quercetin for three weeks before, during, and continuing for two weeks after the 160-km Western
States Endurance Run. In this study, however, there were no differences in the post-race illness rates
between quercetin and placebo groups [75].
There are several studies in humans investigating the correlation of quercetin and its immunomodulatory
effects. Quercetin does indeed reduce illness after intensive exercise. Again, under double-blind
conditions, Nieman et al. showed that a supplement of 1000 mg of quercetin alone three weeks before,
during and two weeks after a three-day period of 3 h of cycling in the winter resulted in a markedly
lower incidence of URTI in well-trained subjects in the two weeks after the intensified training, but
had no effect on exercise-induced immune dysfunction, inflammation and oxidative stress [76].
The literature is supportive of the anti-pathogenic capacities of quercetin when it is cultured with
target cells and a broad spectrum of pathogens including URTI-related rhinoviruses, adenoviruses and
coronaviruses. The impact of the co-ingestion of two or more flavonoids increases their bioavailability and
the outcomes on immunity. Nieman et al. determined the influence of two weeks of 1000 mg/day quercetin
compared with placebo supplementation on exercise performance and skeletal muscle mitochondrial
biogenesis in untrained, young adult males. It resulted in significantly reduced post-exercise measures
for both inflammation and oxidative stress, with a chronic augmentation of granulocyte oxidative burst
activity [
77
]. When taken together, quercetin showed a successful reduction in the illness rates of
exercise-stressed athletes as well as a chronic augmentation of their innate immune function.
Most
in vitro
research suggests that quercetin possesses anti-inflammation and immunological
improvement. However, the results from a double-blinded, placebo-controlled, randomized trial
indicated that quercetin supplementation at 500 and 1000 mg/day for 12 weeks significantly increased
plasma quercetin levels but had no influence on measures of innate immune function or inflammation
in community-dwelling adult females [73].
Nutrients 2016,8, 167 9 of 14
The main action of quercetin on inflammation and immune function
in vivo
is summarized in the
Table 2.
Table 2. Summary of the main effects of quercetin on inflammation and immune function in vivo.
Dosage Subjects Effect Mechanism Reference
Animals
10 mg/kg diet Rat
Anti-inflammation
Modulation of prostanoid synthesis
and cytokine production [60]
0.8% diet C57BL/6J mouse
Increase of energy expenditure;
Decrease of interferon-γ,
interleukin-1α, and interleukin-4
[61]
10 mg/kg of
body weight Zucker rat
Downregulation of visceral
adipose tissue inducible nitric oxide
synthase expression, increase of
endothelial nitric oxide
synthase expression
[62]
160 mg/kg body
weight (oral
administration)
60 mg/kg
(intra-cutaneous
injections)
Lewis rat Inhibition of macrophage-derived
cytokines and nitric oxide [63]
10 and 40 mg/kg
body weight Mouse Increase of cytokine (interleukin-1β
and interleukin-6) secretion [66]
5–100 micromoles /kg
body weight
(administered
intraperitoneally)
25 µmol/kg
Wistar rat Functional recovery of acute
spinal cord injury and motor
function
Decrease of secondary damage
through iron chelation, No effect [64,65]
0.05% diet C57BL/6J mouse
Suppression of the accumulation
and activation of immune cells,
Suppression of oxidative stress and
NFκB activity
[70]
50, 100, 150 mg/kg
body weight Wistar rat Amelioration of immunity
function impairment
induced by isoproterenol;
Amelioration of brain
damage and
neuroprotection,
experimental allergic
encephalomyelitis,
experimental autoimmune
myocarditis
Increase of activity in aspartate
transaminase, creatine kinase,
nitric oxide, nitric oxide synthase,
interleukin-10, interleukin-1,
interleukin-8 and
lactate dehydrogenase
[59]
50 mg/kg Sprague-Dawley
(SD) rat
Increase of activity of endogenous
antioxidant enzymes and inhibition
of free radical generation
[67]
50 or 100 µg SJL/J mice
Blockage of interleukin-12 signaling
and Th1 differentiation [68]
10 or 20 mg/kg (oral
administration) Dark Agouti rat
Interference of pro-inflammatory
(TNF-αand IL-17) and/or
anti-inflammatory (IL-10)
cytokines production
[69]
Human
50 and 100 mg/person Elderly Human
subject
Anti-inflammatory
properties
Inhibition of proteasome (nitric
oxide, C-reactive protein,
γ-glutamyltransferase) activity
[71]
500 and 1000 mg/day Human subject Reduction of upper
respiratory tract infection
and total sick days;
Improvement in 12-min
treadmill time trial
performance
No effect [72]
1000 mg/day Human in
treadmill No effect [76]
500 and 1000 mg/day Human subject
No effect on innate immune
function or inflammation,
illness rates
No effect [73]
1000 mg/day Human cyclist No effect [74]
1000 mg/day Human runner No effect [75]
1000 mg/day Human cyclist No effect [77]
Nutrients 2016,8, 167 10 of 14
These results suggest that quercetin exhibited anti-inflammation and immune-enhancement
in vitro
(cells) and
in vivo
(animals), however, studies in human did not totally support these results
from cells and animals. The effect, in which quercetin acts as an immune booster in humans, needs to
be further verified for future broad application.
6. Summary
As a widespread flavonoid, quercetin is a safe and dietary supplement based on its broad range of
biological effects in animal. The results of these effects are not consistent, however, and the outcomes
need to be carefully evaluated, as they are dependent on the type of subject and their level of health.
Taken together, we know definitively that a quercetin glycoside is much more efficient than other
forms of quercetin. In the majority of the literature, we find references to the benefits of prolonged
supplementation with quercetin.
The future challenge is to investigate optimal benefits of quercetin, especially to the recommendation
for the protracted intake. For example, a carbohydrate drink may have a better effect than pure
quercetin preparation. The research in this area continues to determine the proper outcomes, dosing
regimen and adjuvants that may amplify any perceived bioactive effects of quercetin in vivo.
Acknowledgments:
The authors thank Heilong Department of Education (12541010), Heilongjiang Department
of Human Resources and Social Security (2014–2015), Harbin Science and Technology Bureau (2015RQXXJ014),
the Chinese Academy of Science STS Project (KFJ-EW-STS-063) and Academic Team Construction of Northeast
Agricultural University (2014–2017).
Conflicts of Interest: The authors declare no conflict of interest.
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2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons by Attribution
(CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
... The sugar component is usually bound to the C-ring at various positions (3 , 4 , 5 , 7 ) [3]. Flavonols, like all flavonoids, occur in nature in two forms, either as an aglycone lacking a carbohydrate moiety, or like a glycoside, where the hydroxyl group of the carbonate ring has been replaced by sugars such as glucose, rhamnose, or rutinose [4]. Quercetin has been reported to constitute 60-75% of total dietary flavonoid and flavonol intake [5,6]. ...
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Quercetin belongs to the broader category of polyphenols. It is found, in particular, among the flavonols, and along with kaempferol, myricetin and isorhamnetin, it is recognized as a foreign substance after ingestion in contrast to vitamins. Quercetin occurs mainly linked to sugars with the most common compounds being quercetin-3-O-glucoside or as an aglycone, especially in the plant population. The aim of this review is to present a recent bibliography on the mechanisms of quercetin absorption and metabolism, bioavailability, and antioxidant and the clinical effects in diabetes and cancer. The literature reports a positive effect of quercetin on oxidative stress, cancer, and the regulation of blood sugar levels. Moreover, research-administered drug dosages of up to 2000 mg per day showed mild to no symptoms of overdose. It should be noted that quercetin is no longer considered a carcinogenic substance. The daily intake of quercetin in the diet ranges 10 mg-500 mg, depending on the type of products consumed. This review highlights that quercetin is a valuable dietary antioxidant, although a specific daily recommended intake for this substance has not yet been determined and further studies are required to decide a beneficial concentration threshold.
... The interesting therapeutic potential of quercetin is unfortunately limited to its limited oral bioavailability of about 4%, due to its high lipophilicity and half-life of 3.5 h. Poor bioavailability and therapeutic response due to the rapid metabolism of the drug necessitates high dose and frequent administration leading to patient incompliance [18,19]. To overcome these limitations, various formulations have been developed for quercetin such as microemulsions, self-micro and nano-emulsifying drug delivery systems, phytosomes, micelles, solid lipid nanoparticles, liposomes, etc. [20][21][22][23][24][25]. ...
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Quercetin, a flavonoid, has antioxidant and anti-inflammatory properties and the potential to inhibit the proliferation of cancer, but its therapeutic efficacy is lowered due to poor solubility and bioavailability. Quercetin-loaded nanocochleates (QN) were developed using a trapping method by the addition of calcium ions into preformed negatively charged liposomes (QL) prepared by a thin-film hydration method. Liposomes were optimized by varying the concentration of Dimyristoyl phosphatidyl glycerol and quercetin by applying D-optimal factorial design using Design Expert ® software. Stable rods were observed using TEM with an average particle size, zeta potential and encapsulation efficiency of 502 nm, −18.52 mV and 88.62%, respectively, for QN which were developed from spherical QL showing 111.06 nm, −40.33 mV and 74.2%, respectively. In vitro release of quercetin from QN and QL was extended to 24 h. Poor bioavailability of quercetin is due to its degradation in the liver, so to mimic in vivo conditions, the degradation of quercetin released from QL and QN was studied in the presence of rat liver homogenate (S9G) and results revealed that QN, due to its unique structure, i.e., series of rolled up solid layers, shielded quercetin from the external environment and protected it. The safety and biocompatibility of QL and QN were prov-enby performing cytotoxicity studies on fibroblast L929 cell lines. QN showed superior anticancer activity compared to QL, as seen for human mouth cancerKB cell lines. Stability studies proved that nanocochleates were more stable than liposomal formulations. Thus, nanocochleates might serve as pharmaceutical nanocarriers for the improved efficacy of drugs with low aqueous solubility, poor bioavailability, poor targeting ability and stability. Citation: Munot, N.; Kandekar, U.; Giram, P.S.; Khot, K.; Patil, A. A
... The role of vitamin A in the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and schizophrenia, is currently under investigation [108,111]. Vitamin A has also been studied in association with quercetin, a well-known flavonol (see Section 2.7 Flavonoids) [112]. This combination has proven capable of reducing rapid senescence-like response induced by acute liver injury [113]. ...
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Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.
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Rotavirus (RV) is the leading cause of acute gastroenteritis and watery diarrhea in children under 5 years accounting for high morbidity and mortality in countries with poor socioeconomic status. Although vaccination against RV has been implemented in more than 100 countries, the efficacy of vaccine has been challenged in low-income settings. The lack of any FDA-approved drug against RV is an additional concern regarding the treatment associated with rotavirus-induced infantile death. With the purpose for the discovery of anti-RV therapeutics, we assessed anti-rotaviral potential of quercetin, a well-characterized antioxidant flavonoid. In vitro study revealed that quercetin treatment resulted in diminished production of RV-SA11 (simian strain) viral particles in a concentration-dependent manner as estimated by the plaque assay. Consistent with this result, Western blot analysis also revealed reduced synthesis of viral protein in quercetin-treated RV-SA11-infected MA104 cells compared to vehicle (DMSO) treated controls. Not surprisingly, infection of other RV strains A5-13 (bovine strain) and Wa (Human strain) was also found to be abridged in the presence of quercetin compared to DMSO. The IC50 of quercetin against three RV strains ranges between 2.79 and 4.36 Mm, and S.I. index is greater than 45. Concurrent to the in vitro results, in vivo study in mice model also demonstrated reduced expression of viral proteins and viral titer in the small intestine of quercetin-treated infected mice compared to vehicle-treated infected mice. Furthermore, the result suggested anti-rotaviral activity of quercetin to be interferon-independent. Mechanistic study revealed that the antiviral action of quercetin is co-related with the inhibition of RV-induced early activation of NF-κB pathway. Overall, this study delineates the strong anti-RV potential of quercetin and also proposes it as future therapeutics against rotaviral diarrhea.
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For some classes of dietary polyphenols, there are now sufficient intervention studies to indicate the type and magnitude of effects among humans in vivo, on the basis of short-term changes in biomarkers. Isoflavones (genistein and daidzein, found in soy) have significant effects on bone health among postmenopausal women, together with some weak hormonal effects. Monomeric catechins (found at especially high concentrations in tea) have effects on plasma antioxidant biomarkers and energy metabolism. Procyanidins (oligomeric catechins found at high concentrations in red wine, grapes, cocoa, cranberries, apples, and some supplements such as Pycnogenol) have pronounced effects on the vascular system, including but not limited to plasma antioxidant activity. Quercetin (the main representative of the flavonol class, found at high concentrations in onions, apples, red wine, broccoli, tea, and Ginkgo biloba) influences some carcinogenesis markers and has small effects on plasma antioxidant biomarkers in vivo, although some studies failed to find this effect. Compared with the effects of polyphenols in vitro, the effects in vivo, although significant, are more limited. The reasons for this are 1) lack of validated in vivo biomarkers, especially in the area of carcinogenesis; 2) lack of long-term studies; and 3) lack of understanding or consideration of bioavailability in the in vitro studies, which are subsequently used for the design of in vivo experiments. It is time to rethink the design of in vitro and in vivo studies, so that these issues are carefully considered. The length of human intervention studies should be increased, to more closely reflect the long-term dietary consumption of polyphenols.
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Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease. Objective: Our objective was to investigate the effect of intake of flavonoid-containing black currant and apple juice on urinary excretion of quercetin and on markers of oxidative status. Design: This was a crossover study with 3 doses of juice (750, 1000, and 1500 mL) consumed for 1 wk by 4 women and 1 man corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin/d. Results: Urinary excretion of quercetin increased significantly with dose and with time. The fraction excreted in urine was 0.29–0.47%. Plasma quercetin did not change with juice intervention. Plasma ascorbate increased during intervention because of the ascorbate in the juice. Total plasma malondialdehyde decreased with time during the 1500-mL juice intervention, indicating reduced lipid oxidation in plasma. Plasma 2-amino-adipic semialdehyde residues increased with time and dose, indicating a prooxidant effect of the juice, whereas erythrocyte 2-amino-adipic semialdehyde and γ-glutamyl semialdehyde concentrations, Trolox-equivalent antioxidant capacity, and ferric reducing ability of plasma did not change. Glutathione peroxidase activity increased significantly with juice dose. Conclusions: Urinary excretion of quercetin seemed to be a small but constant function of quercetin intake. Short-term, high intake of black currant and apple juices had a prooxidant effect on plasma proteins and increased glutathione peroxidase activity, whereas lipid oxidation in plasma seemed to decrease. These effects might be related to several components of the juice and cannot be attributed solely to its quercetin content.
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We studied the bioavailability and the plasma transport of flavonols in rats fed quercetin or rutin diets. Wistar rats were fed one of the following purified diets for 10 d: control; 16.4 or 8.2 mmol rutin/kg diet; or 16.4, 8.2 or 4.1 mmol quercetin/kg diet. Flavonol concentrations were determined in plasma, ileal and cecal contents, and feces. In rats fed diets containing 16.4 mmol quercetin or rutin/kg, the concentration of circulating flavonols was ∼115 µmol/L. Quercetin or rutin administration resulted in similar concentrations of quercetin in cecal contents. By HPLC analysis and β-glucuronidase/sulfatase treatment, plasma flavonols have been identified as conjugated quercetin itself, or a conjugated form (4.5-fold as abundant) of an aglycone less polar than quercetin. Rats fed quercetin or rutin diets had a green/yellow-colored plasma that exhibited a peak absorbance at 411 nm, vs. 363 or 375 nm for pure rutin or quercetin solutions, respectively. This shift of band I absorption was obtained when pure quercetin was in the presence of albumin or added to a plasma fraction. The bathochromic properties of flavonoids in the presence of albumin are highly dependent on the presence of the C-2/C-3 double bond on the C-ring and are influenced by the degree of B-ring hydroxylation. The existence of intermolecular bonds between albumin and quercetin is supported by in vitro absorbance and fluorescence studies. With human albumin, the fluorescence intensity and the shift of quercetin absorbance increased in parallel to the albumin/quercetin molar ratio. Conjugated diene formation, resulting from Cu²⁺-catalyzed oxidation of human LDL or rat VLDL+LDL was effectively inhibited in vitro by 0.5 µmol/L quercetin. These results show that dietary flavonols are recovered in rat plasma as conjugated metabolites in non-negligible concentrations, and that these flavonols may be interesting antioxidant micronutrients with a variety of biological effects.
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Estimating flavonoid intake is a first step toward documenting the protective effects of flavonoids against risk of chronic diseases. Although flavonoids are important dietary sources of antioxidants, insufficient data on the comprehensive food composition of flavonoids have delayed the assessment of dietary intake in a population. We aimed to estimate the dietary flavonoid intake in U.S. adults and its sociodemographic subgroups and to document major dietary sources of flavonoids. We expanded the recently released USDA Flavonoid Database to increase its correspondence with the 24-h dietary recall (DR) of the NHANES 1999–2002. We systematically assigned a particular food code to all foods that were prepared or processed similarly. This expanded database included 87% of fruits and fruit juices, 86% of vegetables, 75% of legumes, and, overall, 45% of all foods reported by the 24-h DR of the NHANES 1999–2002. Estimated mean daily total flavonoid intake, 189.7 mg/d, was mainly from flavan-3-ols (83.5%), followed by flavanones (7.6%), flavonols (6.8%), anthocyanidins (1.6%), flavones (0.8%), and isoflavones (0.6%). The flavonoid density of diets increased with age (P < 0.001) and income (P < 0.05). It was higher in women (P < 0.001), Caucasians (P < 0.001), and vitamin supplement users (P < 0.001) and lower in adults with high levels of nonleisure time physical activity (P < 0.01) compared with their counterparts. The greatest daily mean intake of flavonoids was from the following foods: tea (157 mg), citrus fruit juices (8 mg), wine (4 mg), and citrus fruits (3 mg). The proposed relation between flavonoid intake and the prevention of chronic diseases needs further investigation using the estimates introduced in this study.
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Flavonoids are the most numerous group of natural polyphenolic compounds, the secondary metabolites of plants that may play an important role in human health protection. Flavonols and flavones constitute the main two classes of flavonoids, whose antioxidant properties and high biological activity have been proofed both in vitro and in vivo. This review summarizes data, concerning the structure, occurrence and content of the main flavonols (quercetin, kaempherol, myricetin, isorhamnetin) and flavones (apigenin, luteolin) in some most widely consumed foodstuffs, including vegetables, fruits, berries, nuts, beverages and other products of plant origin. The products with high content of these biologically active food compounds--the major dietary sources of them--are noted. Forms of flavonols and flavones more often distributed among edible plants are characterized and some of their known glycosides occurred in foods are enumerated. Some peculiarities, characteristic to flavonol sand flavones glycosilation (O- and/or C-glycosides formation) are described. The data for flavonol and flavone glycosides composition (profiles) of some commonly consumed commodities rich by these flavonoids (onions, cabbage, apples at al.) are shown. Information about levels of daily dietary intake of total and individual flavonols and flavones in several countries is presented. The questions about dietary habits and lifestyle factors and the contribution of certain foods to flavonols and flavones in daily dietary consumption values are also discussed.
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Scientific research is constantly looking for new molecules that could be used as dietary functional ingredients in the fight against obesity and diabetes, two pathologies highly prevalent in Western societies. In this context, flavonoids represent a group of molecules of increasing interest. The major flavonoid is Quercetin, which belongs to the class called flavonols and is mainly found in apples, tea, onions, nuts, berries, cauliflower, cabbage and many other foods. It exhibits a wide range of biological functions including anticarcenogenic, anti-inflammatory and antiviral; it also inhibits lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the main effects of Quercetin on obesity and diabetes. The mechanisms of action explaining the effects of Quercetin on these two metabolic disturbances are also considered. Good perspectives have been opened for Quercetin, according to the results obtained either in cell cultures or in animal models. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of this flavonoid on these pathologies. Moreover, the body fat-lowering effect and the improvement of glucose homeostasis need to be confirmed in humans. Animal studies have consistently failed to demonstrate adverse effects caused by Quercetin. In contrast, due to inhibitory effect of Quercetin in cytochrome P450, interactions with drugs can be taken into account when they are administered at the same time than Quercetin.