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Associative evidence from observational and intervention studies in human subjects shows that a diet including plant foods (particularly fruit and vegetables rich in antioxidants) conveys health benefits. There is no evidence that any particular nutrient or class of bioactive substances makes a special contribution to these benefits. Flavonoids occur naturally in fruits, vegetables and beverages such as tea and wine. Quercetin is the major flavonoid which belongs to the class called flavonols. Quercetin is found in many common foods including apples, tea, onions, nuts, berries, cauliflower, cabbage and many other foods. Quercetin provides many health promoting benefits, including improvement of cardiovascular health, eye diseases, allergic disorders, arthritis, reducing risk for cancers and many more. The main aim of this review is to obtain a further understanding of the reported beneficial health effects of Quercetin, its pharmacological effects, clinical application and also to evaluate its safety.
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Internet Journal of Medical Update, Vol. 2, No. 2, Jul-Dec 2007 Clinical Knowledge
Quercetin: A Versatile Flavonoid
Dr. Parul Lakhanpal*, MD and Dr. Deepak Kumar Rai, MD
*Reader, Department of Pharmacology, SSR Medical College, Mauritius
SMHO, Department of Pediatrics, Ministry of Health & Quality of Life, Mauritius
(Received 04 January 2007 and accepted 29 March 2007)
ABSTRACT: Associative evidence from observational and
intervention studies in human subjects shows that a diet including plant
foods (particularly fruit and vegetables rich in antioxidants) conveys
health benefits. There is no evidence that any particular nutrient or
class of bioactive substances makes a special contribution to these
benefits. Flavonoids occur naturally in fruits, vegetables and beverages
such as tea and wine. Quercetin is the major flavonoid which belongs to
the class called flavonols. Quercetin is found in many common foods
including apples, tea, onions, nuts, berries, cauliflower, cabbage and
many other foods. Quercetin provides many health promoting benefits,
including improvement of cardiovascular health, eye diseases, allergic
disorders, arthritis, reducing risk for cancers and many more.
The main aim of this review is to obtain a further understanding of the
reported beneficial health effects of Quercetin, its pharmacological
effects, clinical application and also to evaluate its safety.
KEY WORDS: Quercetin, Flavonoid, Antioxidant, Health.
INTRODUCTION:
Quercetin is a unique bioflavonoid that has been
extensively studied by researchers over the past
30 years. Bioflavonoids were first discovered by
Nobel Prize laureate Albert Szent Gyorgyi in the
year 1930. Flavonoids belong to a group of
natural substances with variable phenolic
structure and are found in the fruits, vegetables,
grains, bark roots, stem, flowers, tea and wine1.
These natural products were known for their
beneficial effects on health long before
flavonoids were isolated as the effective
compounds. More than 4000 varieties of
flavonoids have been identified, many of which
are responsible for their attractive colors of
flowers, fruits and leaves2.
Flavonoids occur as aglycones, glycosides and
methylated derivatives. The flavonoid aglycone
consists of a benzene ring (A) condensed with a
six membered ring (C), which in the 2-position
carries a phenyl ring (B) as a substituent3. The
Flavonoids can be divided into various classes
on the basis of their molecular structures (Figure
1)4.
Six-member ring condensed with the benzene
ring is either a-pyrone (flavonols and
flavonones) or its dihydroderivative (flavanols
and flavanones). The position of the benzenoid
substituent divides the flavonoid class into
flavonoids (2-position) and isoflavonoids (3-
position). Flavonols differ from flavonones by
hydroxyl group the 3-position and C2-C3 double
bonds5. Flavonoids are often hydroxylated in
position 3, 5, 7, 2’, 3’, 4’, 5’. Methylethers and
acetylesters of the alcohol group are known to
occur in nature. When glycosides are formed, the
glycosidic linkage is normally located in
positions 3 or 7 and the carbohydrate can be L-
rhamnose, D-glucose, glucor-hamnose, galactose
or arabinose6. Flavonoids are mainly divided into
seven major groups (figure-2)7. One of the best
described flavonoids, Quercetin is a member of
this group.
Corresponding Author: Dr. Parul Lakhanpal, Reader, Department of Pharmacology, SSR Medical
College, Belle-Rive, Mauritius, Email: lakhanpalparul@rediffmail.com
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Figure 1: Structures of the major classes of Flavonoid4
Figure 2: Major classes of Flavonoids7
Quercetin is found in abundance in onions,
broccoli, apples and berries. The second group is
flavanones, which are mainly found in citrus
fruits. An example of a Flavonoid in this group is
naringinin. Flavonoids belonging to the catechins
are mainly found in green and black tea and in
red wine, whereas, anthocyanins are found in
strawberries, other berries, grapes, wines and
tea2. Flavonoid contents of different foods are
shown in Table-1.
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Table 1: Main groups of flavonoids, compounds and food sources
Groups Compounds Food sources
Flavonols
Quercetin
Kaempferol
Myricetin
Isorhamnetin
Querctagetin
Yellow onion, Curly kale,
Leek, Cherry tomato,
Broccoli, Apple, Green and
black tea, Black grapes,
Blueberry.
Flavones
Tangeretin
Heptamethoxyflavone
Nobiletin
Sinensetin
Quercetogetin
Chrysin
Apegenin
Luteolin
Disometin
Tricetin
Parsley, Celery, Capsicum
pepper.
Flavanones
Naringenin
Eriodictyol
Hesperetin
Dihydroquercetin
Dihydrofisetin
Dihydrobinetin
Orange juice, Grapefruit
juice, Lemon juice.
Flavanols
Silibinin
Silymarin
Taxifolin
Pinobanksin
Cocoa, Cocoa beverages,
Chocolates.
Catechins
(Proanthocyanidins)
(+) Catechin
Gallocatechin
(-) Epicatechin
Epigallocatechin
Epicatechin 3-gallate
Epigallocatechin 3-gallate
Chocolate, Beans, Apricot,
Cherry, Grapes, Peach, Red
wine, Cider, Green tea, Black
tea, Blackberry.
Isoflavones Daidzein
Genistein
Glycitein
Soy cheese, Soy flour, Soy
bean, Tofu.
Anthocyanins
Cyanidin
Delphinidin
Malvidin
Pelargonidin
Peonidin
Petunidin
Blue berry, Blackcurrant,
Black grapes, Cherry,
Rhubarb, Plum, Strawberry,
Red wine, Red cabbage.
Quercetin, the most abundant of the flavonoids
(the name comes from the Latin –quercetum,
meaning oak forest, quercus oak) consists of 3
rings and 5 hydroxyl groups (Figure-3)8.
Quercetin is a member of the class of flavonoids
called flavonoles and forms the backbone for
many other flavonoids including the citrus
flavonoids like rutin, hesperidins, Naringenin
and tangeritin. It is widely distributed in the
plant kingdom in rinds and barks. Quercetin
itself is an aglycon or aglucone that does not
possess a carbohydrate moiety in its structure.
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Quercetin is typically found in plants as glycone
or carbohydrate conjugates. Quercetin glycone
conjugates include rutin and thujin. Rutin is also
known as Quercetin-3-rutinoside.Thujin is also
known as quercitrin, Quercetin-3-L-rhamnoside
and 3-rhannosyl qurcetin. Onions contain
conjugates of Quercetin and carbohydrate iso
rhamnetin including Quercetin-3-4’-di-o-beta
glucoside, isorhamnetin-4’-o-beta glucoside and
Quercetin-4’-o-beta glucoside.
Figure-2 Molecular structure Quercetin8
MECHANISM OF ACTION:
Anti-oxidative action:
The best described property of Quercetin is its
ability to act as antioxidant. Quercetin seems to
be the most powerful flavonoids for protecting
the body against reactive oxygen species,
produced during the normal oxygen metabolism
or are induced by exogenous damage9,10. One of
the most important mechanisms and the
sequence of events by which free radicals
interfere with the cellular functions seem to be
the lipid peroxidation leading eventually the cell
death. To protect this cellular death to happen
from reactive oxygen species, living organisms
have developed antioxidant line of defense
systems11. These include enzymatic and non-
enzymatic antioxidants that keep in check
ROS/RNS level and repair oxidative cellular
damage. The major enzymes, constituting the
first line of defence, directly involved in the
neutralization of ROS/RNS are: superoxide
dismutase (SOD), catalase (CAT) and
glutathione peroxidase (GPx) The second line of
defence is represented by radical scavenging
antioxidants such as vitamin C, vitamin A and
plant phytochemicals including quercetin that
inhibit the oxidation chain initiation and prevent
chain propagation .This may also include the
termination of a chain by the reaction of two
radicals. The repair and de novo enzymes act as
the third line of defence by repairing damage and
reconstituting membranes. These include lipases,
proteases, DNA repair enzymes and
transferases12.
Direct radical scavenging action:
Free radical production in animal cells can either
be accidental or deliberate. With the increasing
acceptance of free radicals as common place and
important biochemical intermediates, they have
been implicated in a large number of human
diseases13,14. Quercetin acting as free radical
scavengers was shown to exert a protective effect
in reperfusion ischemic tissue damage15,16,17.
Quercetin prevents free radical induced tissue
injury by various ways. One way is the direct
scavenging of free radicals. By scavenging free
radicals, Flavonoid; particularly Quercetin can
inhibit LDL oxidation in vitro18. This action
protects against atherosclerosis.
Inducible nitric oxide syntheses Inhibitory
action:
Quercetin results in a reduction in ischemia –
reperfusion injury by interfering with inducible
nitric oxide synthase activity19. Nitric oxide is
produced by several different types of cells
including endothelial cells and macrophages.
Although the early release of nitric oxide through
the activity of constitutive nitric oxide synthase
is important in maintaining the dilatation of
blood vessels20, the much higher concentration of
nitric oxide produced by inducible nitric oxide
synthase in macrophages can result in oxidative
damage. In these circumstances the activated
macrophages greatly increase their simultaneous
production of both nitric oxide and superoxide
anions. Nitric oxide reacts with free radicals,
thereby producing high damaging peroxynitrite.
Peroxynitrite can directly oxidize LDLs resulting
in irreversible damage to cell membranes.
Quercetin causes scavenging of free radicals;
therefore can no longer react with nitric oxide,
resulting in less damage21. Nitric oxide
interestingly can be viewed as radical itself and
can directly be scavenged by Flavonoids22.
Xanthine oxidase inhibitory action:
The xanthine oxidase pathway has been
implicated as an important route in the oxidative
injury to the tissues especially after ischemia-
reperfusion23. Both xanthine dehydrogenase and
xanthine oxidase are involved in the metabolism
of xanthine to uric acid. Xanthine dehydrogenase
is the form of the enzyme present under
physiological condition but its configuration
changed to xanthine oxidase during oxidative
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stress and ischemic conditions. Quercetin seems
to inhibit xanthine oxidase activity thereby
resulting in decreased oxidative injury19, 24, 25.
Decreasing Leukocyte immobilization:
The immobilization and the firm adhesions of
leukocytes to the endothelial wall is another
major mechanism responsible not only for the
formation of oxygen derived free radicals but
also for the release of cytotoxic oxidants and
inflammatory mediators and further activation of
complement system. Under normal conditions
leukocytes move freely along the endothelial
walls. However during ischemia and
inflammation, various factors mainly endothelial
derived mediators and complement factors may
cause adhesions of the leukocytes to the
endothelial walls, thereby immobilizing them
and stimulating degranulation of neutrophils. As
a result oxidants and inflammatory mediators are
released, resulting in injury to the tissues. Oral
administration of purified micronized flavonoids
fraction was reported to decrease the number of
immobilized leukocytes during reperfusion,
which may be related to its protective
mechanism against inflammatory conditions26.
Modulation of gene expression:
Recent studies indicate that the radical
scavenger property of Quercetin is unlikely to be
the sole explanation for their neuroprotective
capacity and in fact, a wide spectrum of cellular
signaling events may well account for their
biological actions27.
Much recent interest has focused on the potential
of Quercetin to interact with intracellular
signaling pathways such as with the mitogen-
activated protein kinase cascade. The strong
neurotoxic potential of quercetin in primary
cortical neurons may occur via specific and
sensitive interactions within neuronal mitogen-
activated protein kinase and Akt/protein kinase B
(PKB) signaling cascades, both implicated in
neuroal apoptosis. Quercetin induced potent
inhibition of both Akt/PKB and ERK
phosphorylation, resulting in reduced
phosphorylation of BAD and a strong activation
of caspase-327.
Tumor necrosis factor alpha (TNF-α) is one of
the major proinflammatory cytokines involved in
the pathogenesis of chronic inflammatory
diseases and is modulated by oxidative stress28,29.
TNF-α also triggers the cellular release of other
cytokines, chemokines, or inflammatory
mediators and displays antiviral and
antimicrobial effects30,31,32. Quercetin
significantly inhibited TNF-α production and
gene expression in a dose-dependent manner. A
decrease in endogenous TNF-α production in the
presence of quercetin indicates that flavonoids
have the capacity to modulate the immune
response and have potential anti-inflammatory
activity. In addition to its well-known
proinflammatory role, TNF-α has complex
effects on the growth, differentiation, and death
of immune cells. TNF-α inhibition is a validated
approach to treat several inflammatory
diseases28. Quercetin-induced suppression of
TNF-α can result in the stimulation of anti-
inflammatory cytokines via inhibiting the
activation of NF-κβ, and therefore, one can
anticipate that quercetin could be widely used as
an anti-TNF-α therapy. Kaneuchi et al33
showed that quercetin has anti-proliferative
activity and the mechanisms of quercetin action
may be through modulation of cell cycle and cell
growth regulatory genes. Quercetin can suppress
proliferation of Ishikawa cells (endometrial
carcinoma) through down-regulation of EGF and
cyclin D1.
Interaction with other enzyme systems:
Quercetin interacts with calmodulin, a calcium
regulatory protein34. Calmodulin transports
calcium ion across cellular membranes, initiating
numerous cellular process. Quercetin appears to
act as calmodulin antagonist. Through this
mechanism, Quercetin functions at cell
membrane level with a membrane stabilizing
action35. Quercetin inhibits calmodulin
dependent enzyme present at cell membrane
such as ATPases and phospholipases thereby
influencing membrane permeability36. Quercetin
affects other calmodulin dependent enzymes that
control various cellular functions, including the
secretions of histamine from mast cells4. A
number of investigations have demonstrated the
ability of Quercetin, to reduce histamine
secretion from mast cells in various tissues and
also from basophils37-42. The enzyme inhibitory
action of Quercetin extends to phospholipases
which catalyses the release of arachidonic acid
from phospholipids stored in cell membranes.
Arachidonic acid serves as a key substrate for
substances such as thromboxane, inflammatory
prostaglandins and leukotrienes. In addition,
Quercetin also inhibits the enzymes
cyclooxygenase and Lipooxygenase which
catalyses the conversion of arachidonic acid to
its metabolites42,43,44. Reducing levels of these
metabolites as well as histamine levels, is
beneficial in maintaining the normal comfort
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level of body tissue and structures. Quercetin has
also been shown to limit the function of adhesion
molecules on endothelial cells45. Quercetin also
chelates ions of transition metals such as iron
which can initiate the formation of oxygen free
radicals46,47. Direct inhibition of lipid
peroxidation is another protective measures48.
PHARMACOKINETICS:
The metabolism and pharmacokinetics of
flavonoids has been an area of active research in
the last decade. To date, approximately 100
studies have reported the pharmacokinetics of
individual flavonoids in healthy volunteers. The
data indicate considerable differences among the
different types of dietary flavonoids so that the
most abundant flavonoids in the diet do not
necessarily produce the highest concentration of
flavonoids or their metabolites in vivo. Small
intestinal absorption ranges from 0 to 60% of the
dose and elimination half-life (T1/2) range from 2
to 28 h49.
Quercetin is generally believed to be poorly
absorbed. About 25 % of an injected dose of
quercetin is absorbed from small intestine.
Although a recent study by Hollman et al
concludes that humans absorb appreciable
amount of quercetin, contradicts the
assumption50. However, it is found in human
plasma as conjugates with glucuronic acid,
sulfate or methyl groups, with no significant
amounts of free quercetin. Quercetin was found
to reach 0.1-10 µmol/lit (micromole per liter) in
the circulation. The concentration of quercetin
was mainly due to the presence of quercetin
metabolites rather than its aglycon as recently
revised by Murota and Terao51. Regarding the
pharmacokinetics of quercetin glucosides
conjugates; it seems that the main determinant of
absorption of these conjugates is the nature of
the sugar moiety. For example quercetin
glucoside is absorbed from small intestine,
whereas quercetin rutinosides is absorbed from
the colon after the removal of carbohydrate
moiety by bacterial enzymes. In addition to the
chemical form of the flavonol, the fat content of
the diet also influences oral bioavailability of
quercetin. Lesser et al investigated the influence
of dietary fat on oral bioavailability of quercetin.
According to the them, Quercetin bioavailability
from each diet was always higher from the
glucoside than from the aglycon but irrespective
of the chemical form applied, the bioavailability
of quercetin was also found to be higher in the
17% fat diet compared with the 3% fat diet (P <
0.05)52.
Studies have shown that Bromelain, an enzyme
derived from pineapple, enhances the absorption
of quercetin. Bromelain is a complex substance
largely composed of proteolytic enzymes.
Several studies have presented the evidence that
bromelain is a fibrinolytic agent53, 54. Bromelain
is also known to have many of the same
histamine and Leukotriene-inhibitory properties
as quercetin. In this way they enhance each other
properties.
After getting absorbed in small intestine,
quercetin is transported to the liver via portal
circulation, where it undergoes first pass
metabolism. Quercetin and its metabolites are
distributed to various tissues in the body.
Quercetin is strongly bound to the albumin in
plasma. Peak plasma level reaches in 0.7 h to 7.0
hours following its ingestion. The elimination
half life of quercetin is approximately 25 hours55.
The elimination of quercetin was significantly
delayed after its application with fat-enriched
diets (P < 0.05)52.
ADVERSE DRUG REACTION:
Adverse effects reported with oral quercetin
include gastrointestinal effects such as nausea
and rare reports of headache and mild tingling of
the extremities. Oral quercetin is generally well
tolerated. Intravenous quercetin has been
associated with nausea, vomiting, diaphoresis,
flushing, and dyspnoea.
Safety Profile:
There is much controversy regarding the
purported toxic or even mutagenic properties of
quercetin. Formica and Regelson gave an
interesting overview of quercetin in vivo and in
vitro56. The early data on toxic side effects are
mainly derived from in vitro studies. At a
conference of the Federation of American
societies for experimental biology in 1984 on
mutagenic food flavonoids, carcinogenicity was
reported in just one out of 17 feeding studies
conducted in laboratory animals57, 58. Dunnick
and Hailey reported that high doses of quercetin
over several years might result in the formation
of tumors in mice59. However, back in the 1970s,
quercetin was found to have mutagenic activity
as determined by the in vitro Ames test, which
was developed by researcher Bruce Ames to test
if a natural or synthetic substance will cause
DNA mutations in bacteria60. However in other
long term study, no carcinogenicity was found61.
In contrast to earlier studies several more recent
reports indicate that quercetin is antimutagenic in
vivo56, 62, 63. A large clinical study by Knekt et
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al, in which 9959 men and women were
followed for 24 years, showed an inverse
relationship between the intake of quercetin and
lung cancer64. One possible explanation for these
conflicting data is that quercetin is toxic to
cancer cells or immortalized cells but not toxic to
normal cells. In other studies quercetin was also
recognized as genoprotective against mutagenic
agents65, 66. Review of the total body of available
data on quercetin as presented in several
published reviews indicates that quercetin,
although displaying mutagenic activity in vitro is
not carcinogenic in the body. In a number of
studies such as Formica and Regelson56,
Stavric58, Stoewsand67, and recently
Okamoto68, a review of quercetin safety based
on past animal toxicity studies, concluded that
orally administered quercetin is unlikely to cause
any adverse effects although specific dose levels
were not indicated.
CONTRAINDICATIONS AND
PRECAUTIONS:
Contraindication of Quercetin is not known.
Quercetin has been shown to cause chromosomal
mutations in certain bacteria in test tube studies.
However the significance of this finding for
humans is not clear Because of lack of the
availability of long term safety data, quercetin
should be avoided by pregnant women and
nursing mothers.
DRUG INTERACTIONS:
Quercetin shows interaction with following
drugs:
Felodipine:
Quercetin (found in grapefruit juice, tea, onions,
and other foods) has been shown in test tube
studies to inhibit enzymes responsible for
breaking down of Felodipine into inactive forms.
This interaction may result in increased blood
levels of felodipine that could lead to unwanted
side effects69. Until more is known about this
interaction, patients taking felodipine should
avoid supplementing with quercetin. Regular
consumption of grapefruit juice can increase the
quantity of felodipine in the blood by reducing
the breakdown of the drug. The inhibitory effect
of grapefruit juice lasts up to 24 hours after
ingestion and can increase the blood levels
nearly three times the expected amount. In order
to prevent the side effects, individuals taking
felodipine should avoid consuming grapefruits
and its juice70.
Estrogens:
Studies have shown that grapefruit juice
significantly increases estradiol levels in the
blood71,72. One of the flavonoids found in
grapefruit juice is Quercetin. In a test tube study,
quercetin was found to change estrogen
metabolism in human liver cells in a way that it
increases estradiol level and reduces other forms
of estrogens72. However the levels of quercetin
used to alter estrogen metabolism in the test tube
were much higher than the levels found in the
body after supplementing with quercetin.
In a small controlled study of women with
surgically removed ovaries, estradiol levels in
the blood were significantly higher after taking
estradiol with grapefruit juice than when
estradiol was taken alone71. These results have
independently confirmed that women taking oral
estradiol should probably avoid grapefruits
altogether72.
Cyclosporine:
In a randomized study of nine adults with
cyclosporine treated auto-immune diseases,
grapefruit juice causes a significant increase in
cyclosporine blood levels compared with
cyclosporine with water74. In another study by
healthy human volunteers, supplementing
quercetin along with cyclosporine significantly
increased blood level of cyclosporine compared
to when not taken quercetin75.
Quinolones:
Quercetin binds in vitro with DNA gyrase site in
bacteria. Therefore theoretically it can serve as
competitive inhibitor to the Quinolones, which
also bind to the same site76.
Cisplatin:
Because of the theoretical risk of genotoxicity in
normal tissues, in those using cisplatin along
with quercetin, cisplatin users should avoid
quercetin supplements.
Doxorubicin:
Test tube and animal studies suggest that
quercetin may enhance the effect of doxorubicin.
Digoxin:
Treatment with both Digoxin and Quercetin may
result in large amounts of digoxin in blood,
which may cause more side effects of digoxin
than usual. This interaction has been reported in
animals, but how it affects people, is unclear80.
DIETARY SOURCES:
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29
Fruits and vegetables particularly citrus fruits,
apples, onions, parsley, tea, red wine, etc. are the
primary dietary sources of Quercetin. Olive oil,
grapes, dark cherries, and dark berries such as
blueberries and bilberries are also high in
flavonoids including quercetin.
Studies were conducted on the Flavonoids
(Myricetin, Quercetin, Kaempferol, Luteolin and
Apegenin) contents of 62 edible tropical plants.
The highest total flavonoids contents were found
in onion leaves (1497 mg/Kg Quercetin, 391
mg/kg Luteolin and 832 mg/kg Kaempferol)
followed by semambu leaves, bird chillies, black
tea, papaya shoots and guava. Major flavonoids
content in these plant extract is quercetin,
followed by myricetin, and kaempferol. In
vegetables quercetin glycosides predominate but
glycosides of kaempferol, luteolin and apigenin
are also present. Fruits contain almost
exclusively quercetin glycosides, whereas
kaempferol and myricetin glycosides are found
only in trace quantities78. Table-2 shows
contents of Quercetin, Myricetin and Kaempferol
in selected food79.
Table 2: Amount of Quercetin in selected food79
FOOD Quercetin
mg/100g Myricetin
mg/100g Kaempferol
mg/100g
Broccoli, Raw 2.8 0.0 6.3
Carrots, Raw 0.4 0.0 0.0
Celery, Raw 3.5 ---- ----
Cocoa powder, Unsweetened 20.1 ---- ----
Cranberries, Raw 14.0 4.3 0.1
Kale, Raw 5.1 0.0 14.6
Lettuce, Looseleaf, Raw 2.0 0.0 0.0
Lingonberries, Raw 11.3 0.0 0.0
Onions, Raw 22.6 0.0 0.3
Tomatoes, Red ripe, Raw 0.5 0.0 0.1
In another study, content of quercetin was
estimated in 25 edible berries. Sixteen species of
cultivated berries and nine species of wild berries
were collected in Finland in 1997. Quercetin was
found in all the berries such as bog whortleberry
(158 mg/kg fresh weight), lingon berry (74 and
146 mg/kg), cranberry (83 and 121 mg/kg),
chokeberry (89 mg/kg), sweet rowan (85 mg/kg),
rowanberry (63 mg/kg), sea buckthorn berry (62
mg/kg) and crowberry (53 and 56 mg/kg)80.
Onions (Allium cepa L) ranked highest in
quercetin content in a survey of 28 vegetables
and 9 fruits81, 82. Quercetin levels tend to be
highest in red and yellow onions and lowest in
white onions83, 84. Amount of quercetin in onions
vary with bulb color type and variety. Regardless
of onion bulb pigmentation, quercetin
concentration is highest in the outer rings85, 86.
However in another study, more than 60 fresh
fruits, vegetables, and nuts were collected from
four regions across the United States at two
times of the year. Sample collection was
designed and implemented by the Nutrient Data
Laboratory (USDA), using a hydrolysis method
for the anthocyanidins, flavones, and flavonols
and a direct extraction method for the flavan-3-
ols and flavanones. This study showed that the
variation in the flavonoid content of foods, as
purchased by the U.S. consumer, is very large.
The relative standard deviation, averaged for
each flavonoid in each food, was 168%87.
THERAPEUTIC USES:
Quercetin offers a variety of potential therapeutic
uses primarily in the prevention and the
treatment of the conditions listed below.
Quercetin seems to work better when it is used in
conjunction with bromelain, a digestive enzyme
found in pineapple.
Allergies, asthma, hay fever and hives:
Quercetin might be useful in some of the
allergies such as hay fever, hives. It inhibits the
production and release of histamine and other
allergic/inflammatory substances possibly by
stabilizing cell membranes of mast cells86,88.
Mast cells have been proposed as an immune
gate to the brain, as well as sensors of
environmental and emotional stress, and are
likely involved in neuropathologic processes
Internet Journal of Medical Update, Vol. 2, No. 2, Jul-Dec 2007 Clinical Knowledge
such as multiple sclerosis. Among mast cell
products, the protease tryptase could be
associated with neurodegenerative processes
through the activation of specific receptors
(PARs) expressed in the brain, while interleukin
(IL)-6 likely causes neurodegeneration and
exacerbates dysfunction induced by other
cytokines; or it could have a protective effect
against demyelinisation. In the year 2006 a study
conducted by Kempuraj et al showed that
quercetin, a natural compound able to act as an
inhibitor of mast cell secretion, causes a decrease
in the release of tryptase and IL-6 and the down-
regulation of histidine decarboxylase (HDC)
mRNA from human mast cell (HMC)-1. As
quercetin dramatically inhibits mast cell tryptase,
IL-6 release and HDC mRNA transcription by
HMC-1 cell line, these results nominate
quercetin as a therapeutical compound in
association with other therapeutical molecules
for neurological diseases mediated by mast cell
degranulation89.
Antibacterial activity:
Quercetin seems to exert antibacterial activity
against almost all the strains of bacteria known
to cause respiratory, gastrointestinal, skin and
urinary disorders90.
Arthritis:
Quercetin inhibits both cyclo-oxygenase and
lipo-oxygenase activities thus diminishing the
formation of inflammatory mediators91,92. In
addition there are reports of people with
rheumatoid arthritis, who experienced an
improvement in their symptoms, when they
switched from a typical western diet to a vegan
diet with lots of uncooked berries, fruits,
vegetables containing amongst other
antioxidants, quercetin93.
Cancers:
Although the etiology of cancer may be
multifactorial (e.g. diet, genetic, environment),
there is wide recognition that reactive oxygen
and nitrogen species (ROS/RNS) play a pivotal
role in the pathophysiological process.
ROS/RON have been shown to be carcinogenic
and may exert their deleterious effects by
causing DNA damage, alter cell signaling
pathways (MAPK, NFkB, AP-1, PLA, ASK-1)
and modulate gene expression (proto-oncogene,
tumour suppressor gene). The evidence from in
vitro and in vivo laboratory studies, clinical trials
and epidemiological investigations show that
plant-based diets have protective effects against
various cancers. Indeed it has been suggested
that about 7-31% of all cancers could be reduced
by diets high in fruits and vegetables94.
In various animal and test tube studies, quercetin
has been shown to inhibit the growth of cancer
cells including those from breast, colon, prostate
and lung cancers63. Quercetin by virtue of its
anti-oxidant property prevents reactive oxygen
species induced DNA damage, leading to
mutational changes. A large clinical study
suggested the presence of an inverse association
between quercetin intake and subsequent
incidence of lung cancers64. In the study done by
Caltagirone et al, quercetin showed the
inhibitory effect on the growth of melanoma and
also influenced the invasive and metastatic
potential in mice95. The bioflavonoid quercetin
may be a potent alternative to reduce cisplatin
induced nephrotoxicity96. Furthermore quercetin
seems to inhibit angiogenesis97. Angiogenesis is
normally a strictly controlled process in the
human body. Pathological, unregulated
angiogenesis occurs in cancers98. Among the
angiogenesis inhibitors quercetin seems to play
an important role99. However the mechanism
behind the anti-angiogenic effect of flavonoids is
unclear. A possible mechanism could be the
inhibition of protein kinase100. As many of the
PTKs are oncogenes, this raised the possibility of
quercetin being an effective anti-cancer
compound. Quercetin was effective in inhibiting
radiation-induced PKC activity. Activation of
PKC is one of the means of conferring
radioresistance on a tumour cell. Suppression of
PKC activity by Quercetin may be one of the
means of preventing the development of
radioresistance following radiotherapy101.
Coronary Heart Diseases:
Anti-oxidant quercetin intake protects against
coronary heart disease (CHD), caused by
oxidized LDL (bad cholesterol). Hertog et al
stated that regular consumption of flavonoids in
the food might reduce the risk of deaths from
CHD in elderly men102,103. Furthermore a
Japanese study reported an inverse correlation
between quercetin intake and total plasma
cholesterol concentration104. Quercetin was also
shown to be effective inhibitor of platelets
aggregation in dogs and monkeys105. The main
antiplatelet aggregating effect is because of the
inhibition of thromboxane A2106. Quercetin
inhibits the proliferation and migration of aortic
smooth muscle cells, and platelet aggregation
along with the inhibition of mitogen–activated
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protein kinase phosphorylation. These findings
provide new insights and a rationale for the
potential use of quercetin in the prevention of
cardiovascular diseases107.
Diabetic complications:
Quercetin has been found to be an inhibitor of
the enzyme aldose reductase, which plays a role
in converting glucose (sugar) to sorbitol (a sugar
alcohol) in the body. People with diabetes
develop secondary problems, such as
neuropathy, retinopathy, diabetic cataracts, and
nephropathy because of sorbitol buildup in the
body. Quercetin may therefore be beneficial in
the nutritional management of diabetes, but
clinical studies need to be conducted to verify
these effects, which have been observed in non-
human experiments108.
Eye disorders:
Free radicals are thought to contribute the
development of certain disorders including
cataracts and macular degeneration. Quercetin
prevents and treats these eye conditions by
neutralizing these free radicals. In a study of
3,072 adults with the symptoms of macular
degeneration, moderate red wine consumption (a
source of quercetin) offered some protection
against the development and the progression of
the disease109. Regular consumption of dark
berries offers benefits for preventing macular
degeneration110.
Gout:
Quercetin by virtue of its xanthine oxidase
inhibitory nature prevents the production of uric
acid, thereby easing the gout symptoms24, 25.
Neurodegenerative disorders:
According to a study conducted by researchers at
Cornell University in New York, a potent
antioxidant (quercetin) in apples and in
vegetables appear to protect brain cells against
oxidative stress, a tissue damaging process
associated with Alzheimer and other
neurodegenerative disorders111. Quercetin seems
to protect the brain functions by inhibiting the
formation if fibrillated amyloid–beta, the senile
plaque found in Alzheimer’s brain106. An
experiment was performed to demonstrate the
possible effects of quercetin on cognitive
performance of young and aged, ethanol
intoxicated mice (animal model), where chronic
quercetin treatment had shown the reversal of
cognitive deficits112. Even though quercetin is
relatively stable during cooking, fresh apples are
always better sources of quercetin than cooked or
processed apples because the compound is
mainly concentrated in the skin of apples. In
general red apples tend have more of antioxidant
than green or yellow ones. Quercetin, through its
COMT and MAO enzymes inhibiting properties,
might potentiate the anticatabolic effect of L-
dopa plus carbidopa treatment. The results of the
present study strongly suggest that quercetin
could serve as an effective adjunct to L-dopa
therapy in Parkinson disease113. Quercetin has
potential for the treatment of neuroleptic-induced
extrapyramidal side effects, such as from
haloperidol114. Quercetin also is a powerful
antioxidant that may protect brain cells from
damage.
Osteoporosis:
In an English study, bone mineral density was
compared between elder women, who consumed
tea and those who did not. Women in the study,
who drank tea (quercetin), had higher bone
mineral density measurements than those who
did not drink tea. Quercetin in the tea might be
responsible for the prevention of osteoporosis115.
Peptic Ulcer:
Quercetin seems to play a very important role in
the prevention and treatment of peptic ulcer. It
acts by promoting mucus secretion, thereby
serves as gastroprotective agent. Apparently,
many peptic ulcers can be caused by infectious
bacteria, known as Helicobacter pylori.
Quercetin has been shown to inhibit the growth
of this bacterium in in-vitro studies116,117.
Prostatitis:
In a prospective double-blind placebo controlled
study, quercetin was found to be helpful in
category III chronic prostatitis (non bacterial
chronic prostatitis and prostodynia). Thirty men
with this disorder received either placebo or 500
mg of quercetin twice daily for one month.
Significant improvement was achieved in treated
group, as measured by the National Institute of
Health Chronic Prostatitis score118. In a follow
up unblind open study, additional men received
the same amount of quercetin for one month, but
this time quercetin was combined with bromelain
and papain, which may enhance its absorption. In
this study 82% achieved a minimum 25%
improvement score.
Viral infections:
The antiviral effect of Flavonoid was shown in a
study conducted by Wang et al119. Some of the
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viruses reported to be affected by Flavonoids are
herpes simplex virus, respiratory syncitial virus
and adenovirus. Quercetin was reported to
exhibit both anti-infective and antireplicative
abilities. By far most of the studies were
performed in vitro and little is known about the
antiviral effect of flavonoids in vivo. There is
some evidence that flavonoids in their glycon
form seem to be more inhibitory effect on
rotavirus infectivity than flavonoids in their
aglycon form120. Because of the worldwide
spread of HIV, since 1980s, the investigations of
the antiviral activity of flavonoids have mainly
focused on HIV. The discovery and the
development of flavonoids as anti-HIV agents
have expanded in the past two decades. Most of
the studies focused on the inhibitory activity of
reverse transcriptase or RNA directed DNA
polymerase but antiintegrase and antiprotease
activities were also reported. Flavonoids have
mainly been studied in vitro experiments;
therefore no clear contribution of flavonoids to
the treatment of HIV infected patients has yet
been shown121, 122.
PREPARATION AND DOSAGES:
The average diet can supply 15 to 40mg of
quercetin per day from fruit and vegetable
consumption. Increasing quercetin intake for
general health reasons can be accomplished by
simply eating more vegetables and fruit.
However, as most people are confronted with the
reality of not being able to maintain an adequate
intake of bioflavonoid from food sources, extra
quercetin can be obtained from dietary
supplements. For therapeutic purposes such as
allergy management, anti-inflammatory
treatment, and disease treatment, higher dosages
of quercetin are usually prescribed. Therapeutic
dosages can range from 250 to 500mg three
times per day. Quercetin is available in the form
of capsules (250 mg, 300 mg, and 500mg) and
tablets (50 mg, 250 mg, and 500mg).
Recommended adult dosages of quercetin vary
depending on the health condition being treated.
For allergic conditions, 250-600 mg per day in
divided doses and for chronic hives, 200-400 mg
thrice daily quercetin is recommended123.
FUTURE IMPLICATIONS:
Various cohort studies indicated an inverse
association between Flavonoids intake
(Quercetin) and coronary heart disease mortality.
These studies are promising and indicate that
flavonoids may be useful food compounds.
Flavonoids have received much attention in the
literature over the past 10 years and a variety of
potential beneficial effects have been elucidated.
However, most of the studies have been
conducted in vitro studies; therefore, it is difficult
to draw definite conclusion about the usefulness
of flavonoids in the diet. Furthermore,
insufficient methods are available to measure
oxidative damage in vivo and the measurement
of objective endpoints remains difficult.
Although recently some studies124,125,126 have
been conducted on absorption and excretion of
flavonols including quercetin but there is a need
to improve analytic techniques to allow
collection of more data in this aspect. Data on
the long-term consequences of chronic quercetin
ingestion are especially scarce. To conclude, in-
vivo studies could be performed to give a hopeful
picture for the future. Currently, the intake of
fruit, vegetables, and beverages (e.g., tea and
moderate amounts of red wine) containing
quercetin is recommended, although it is too
early to make recommendations on daily
quercetin intakes.
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... Flavonoids are natural products belonging to a category of polyphenolic compounds with more than 4,000 varieties. These compounds are found in the normal human diet, particularly plants and most of them are known for their role in the color of flowers, fruits, and leaves (Lakhanpal & Rai, 2007). ...
... Flavonoids are phenolic structures found in the fruits, bark roots, vegetables, tea, grains, stem, and flowers (Lakhanpal & Rai, 2007). UR is a member of flavonoids obtained from quercetum (oak forest) and has been extensively used since 1857 (Fischer, Speth, Fleig-Eberenz, & Neuhaus, 1997). ...
... Indeed, it directly scavenges free radicals such as reactive oxygen/ nitrogen species (ROS/RNS). Moreover, QUR inhibits the activity of xanthine oxidase which leads to oxidative damage during injury, ischemia, and oxidative stress (Alrawaiq & Abdullah, 2014;Lakhanpal & Rai, 2007). Furthermore, it inhibits the lipid peroxidation, prevents the chain propagation, and reduces the production of more free radicals (Jia, Lin, Mi, & Zhang, 2011;Lakhanpal & Rai, 2007). ...
Article
Over the last few decades, using natural products has been increased to treat different diseases. Today, great attention has been pointed toward the usage of natural products such as flavonoids, especially Quercetin (QUR), in the treatment of diseases. QUR as a natural antioxidant has been traditionally used to prevent or treat a variety of diseases such as cancer, cardiovascular disease, polycystic ovary syndrome (PCOS), obesity, chronic inflammation, and reproductive system dysfunction. Several studies demonstrated that QUR acts as an anti-inflammatory, anti-apoptotic, antioxidant, and anticancer agent. With this in view, in this study, we intended to describe an overview of the biological effects of QUR on the ovary. QUR improves the quality of oocytes and embryos. It affects the proliferation and apoptosis and decreases the oxidative stress in granulosa cells (GCs). Furthermore, QUR can be used as a complementary and alternative therapy in ovarian cancer and it has beneficial effects in the treatment of PCOS patients. It seems that QUR as a supplementary factor has different activities for the treatment of different disorders and it also has bidirectional activities. However, further investigations are needed for understanding the efficacy of QUR in the treatment and improvement of gynecological patients.
... Kuersetin merupakan flavonoid yang termasuk dalam kelompok flavonol. 32 Kuersetin dilaporkan memiliki efek anti inflamasi. 32 Kuersetin dapat menurunkan imobilisasi dan adhesi leukosit ke dinding endotel. ...
... 32 Kuersetin dilaporkan memiliki efek anti inflamasi. 32 Kuersetin dapat menurunkan imobilisasi dan adhesi leukosit ke dinding endotel. 32,33 Selain itu kersetin dan vitamin C juga bertindak sebagai antioksidan yang dapat menghambat oksidasi Low Density Lipoprotein (oxLDL) yang dianggap sebagai pemicu proses inflamasi pada jaringan endotel dan inisiator aterosklerosis. ...
... 32 Kuersetin dapat menurunkan imobilisasi dan adhesi leukosit ke dinding endotel. 32,33 Selain itu kersetin dan vitamin C juga bertindak sebagai antioksidan yang dapat menghambat oksidasi Low Density Lipoprotein (oxLDL) yang dianggap sebagai pemicu proses inflamasi pada jaringan endotel dan inisiator aterosklerosis. 34 ...
Article
Latar belakang: Daun kelor (Moringa oleifera Lam) dilaporkan memiliki sifat antiinflamasi karena mengandung vitamin, mineral, serta kuersetin. Hiperurisemia dapat memicu respon inflamasi yang salah satunya ditandai dengan meningkatnya jumlah leukosit.Tujuan:Menganalisis pengaruh pemberian seduhan daun kelor dengan dosis 3,27 g/kgBB terhadap jumlah leukosit tikus wistar jantan.Metode:Penelitian true experimental dengan pre-post test randomized control group design pada 12 tikus wistar jantan usia 8-12 minggu yang dibagi menjadi 2 kelompok secara acak masing-masing 6 ekor. Kelompok K (Kontrol) dan P (Perlakuan) diberi otak kambing 2g/ekor/hari selama 8 hari. Setelah itu kontrol diberi pakan standar dan akuades, sedangkan perlakuan diberi 3,6 ml seduhan daun kelor selama 14 hari. Pemeriksaan darah dilakukan sebanyak 3 kali, yaitu sebelum dan sesudah pemberian otak kambing dan sesudah pemberian seduhan daun kelor.Hasil: Terdapat penurunan kadar asam urat yang signifikan pada kelompok kontrol (p=0,002), namun tidak terdapat perbedaan signifikan pada kelompok perlakuan (p=0,086) setelah pemberian otak kambing. Perbedaan signifikan terjadi pada jumlah leukosit pada kelompok kontrol (p=0,005) dan perlakuan (p=0,015) setelah pemberian otak kambing. Hal ini menunjukkan tidak terdapat hubungan antara kadar asam urat dan jumlah leukosit (p=0,65). Terdapat perbedaan signifikan pada jumlah leukosit kelompok perlakuan (p=0,008) maupun kontrol (p=0,004) setelah pemberian seduhan daun kelor, namun penurunan rerata lebih besar pada kelompok perlakuan.Kesimpulan:Pemberian seduhan daun kelor dengan dosis 3,27 g/kgBB selama 14 hari dapat menurunkan jumlah leukosit tikus secara signifikan
... The mixture is then shaken vigorously in the dark at room temperature for 30 min [28]. Results are processed either as an equivalent of a standard reference (Trolox, gallic acid, ascorbic acid, BHA, BHT) or IC 50 . ...
... The latter anion will be discussed later. Many studies have shown that flavonoids can rapidly scavenge NO • radicals [49,50]. ...
Article
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Currently, there is a growing interest in screening and quantifying antioxidants from biological samples in the quest for natural and effective antioxidants to combat free radical-related pathological complications. Antioxidant assays play a crucial role in high-throughput and cost-effective assessment of antioxidant capacities of natural products such as medicinal plants and food samples. However, several investigators have expressed concerns about the reliability of existing in vitro assays. Such concerns arise mainly from the poor correlation between in vitro and in vivo results. In addition, in vitro assays have the problem of reproducibility. To date, antioxidant capacities are measured using a panel of assays whereby each assay has its own advantages and limitations. This unparalleled review hotly disputes on in vitro antioxidant assays and elaborates on the chemistry behind each assay with the aim to point out respective principles/concepts. The following critical questions are also addressed: (1) What make antioxidant assays coloured? (2) What is the reason for working at a particular wavelength? (3) What are the advantages and limitations of each assay? and (4) Why is a particular colour observed in antioxidant-oxidant chemical reactions? Furthermore, this review details the chemical mechanism of reactions that occur in each assay together with a colour ribbon to illustrate changes in colour. The review ends with a critical conclusion on existing assays and suggests constructive improvements on how to develop an adequate and universal antioxidant assay.
... Yapı üçlü bir karbon köprüsü (C halkası) ile bağlı olan iki fenil (A ve B halkaları) halkasından oluşur [32]. Flavonoidler çoğu kez 3, 5, 7, 2', 3', 4', 5' pozisyonlarında hidroksillenmişlerdir [33]. ...
... Polimerizasyon derecesi 2 ile 48 birim aralığında olabilir. Elma, kakao, üzüm (Vitis vinifera L.) [36], fasülye, kayısı (Armeniaca vulgaris Lam.), kiraz (Prunus avium), şeftali, kırmızı şarap, yeşil çay (Camellia sinersis), siyah çay, böğürtlen (Rubus caesius) ve bunun gibi birçok ürün proantosiyanidinleri içerir [33]. ...
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Özet Günümüzde doğal renklendiriciler gösterdikleri çeşitli antioksidan, antibakteriyal, antimikrobiyal v.b. aktivitelerinden ve bazı sentetik renklendiricilerin insan sağlığı üzerinde olumsuz etkilerinin gün yüzüne çıkmasından beridir ilgi odağı haline gelmişlerdir. Bu çalışmada, doğal renklendiricilerin kaynakları, sınıflandırılmaları ve kimyasal bileşenleri tartışılmıştır. Abstract Nowadays natural colourants which have various antioxidant, antibacterial, antimicrobial, etc. activities have been point of interest since the emerged negative effects upon human health of some synthetic colourants. In this study, chemical components, types and sources of natural colourants were discussed.
... Quercetin is one of the most often isolated the flavonoids (flavonol class) from plant materials. A broad spectrum of its biological activity, including antioxidant, anti-inflammatory, anti-aggregative, hypotensive, antihypercholesterolemic, anti-cancer, and antimicrobial properties, is the basis of recommendation to consume quercetin-rich foods for pro-health function [25][26][27][28]. As it was described in the literature anti-inflammatory effect of quercetin results mainly from the ability to direct scavenging of free radicals (anti-oxidative action) and to inhibit the activity of cyclooxygenase 2 and lipoxygenase-the enzymes participating in prostaglandins and leukotrienes formation [25][26][27]. ...
... A broad spectrum of its biological activity, including antioxidant, anti-inflammatory, anti-aggregative, hypotensive, antihypercholesterolemic, anti-cancer, and antimicrobial properties, is the basis of recommendation to consume quercetin-rich foods for pro-health function [25][26][27][28]. As it was described in the literature anti-inflammatory effect of quercetin results mainly from the ability to direct scavenging of free radicals (anti-oxidative action) and to inhibit the activity of cyclooxygenase 2 and lipoxygenase-the enzymes participating in prostaglandins and leukotrienes formation [25][26][27]. The effect of quercetin on metabolic processes of activated immunocompetent cells, such as pro-inflammatory macrophages M1, particularly its ability to reprogramming of tricarboxylic acids cycle by decreasing succinate and increasing citrate, was proposed as molecular basis for anti-inflammatory activity of this flavonoid [8]. ...
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Biological potential of plant extracts are widely described. Because their oral or topical administration is usually recommended, intestinal mucous and skin are the first surfaces exposed to such preparations. Therefore, we asked the question whether phenolic and non-polar fractions of the extracts from fruits, twigs, and leaves of sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) would be able to modulate the functions of human physiological barrier. The study was carried on caucasian colon epithelial-like Caco-2 cells and human foreskin fibroblasts HFF-1 line. Cell secretory activity (ELISA), the expression of cell surface molecules (flow cytometry), cell migration during wound healing in vitro (scratch assay) were assessed. It was demonstrated for the first time, that sea buckthorn extracts can improve intestinal and skin barrier by increasing of ICAM-1 expression on colon epithelial cells and intensification of IL-8 production by fibroblasts. On the other hand, an inhibition of fibroblasts migration in the presence of those preparations was noted. Therefore, greater attention should be paid on precise description of plant extracts effect depended on target cells and their role to give adequate recommendations for such preparations use.
... The toxicity of NO increases greatly when it reacts with the superoxide radical, forming the highly reactive peroxynitrite anion (ONOO−) (Amaeze et al., 2011). Nitric oxide has been shown to be directly scavenged by flavonoids (Lakhanpal and Rai, 2007). Due to the reactivity of TBA with several reactive substances in a biological sample, a more widely accepted terminology called TBARS is now commonly used (Sun et al., 2001). ...
Article
Full-text available
Background: Dialium guineense belongs to the Leguminosae family, and grows in dense forests in Africa along the southern edge of the Sahel. The bark, leaves and fruits of the plant have medicinal properties and are used to treat diseases such as stomatitis, toothache, fever, diarrhoea, palpitations, and microbial infections. Aim: The present study investigated the free radical scavenging activities of aqueous and ethanol extracts of Dialium guineense stem bark. Methods: Aqueous and ethanol extracts of D. guineense stem bark were prepared using standard method. The in vitro antioxidant activities of the extracts were also determined using standard methods. Results: The diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity and total antioxidant capacity (TAC) of the ethanol extract were significantly higher than those of aqueous extract (p < 0.05). However, there were no significant differences in their nitric oxide (NO) scavenging activity, thiobarbituric acid (TBARS), and reductive potential (p > 0.05). The ferric reducing antioxidant power (FRAP) of the aqueous extract was significantly higher than those of ethanol extract and ascorbic acid (p < 0.05). Conclusion: These results suggest that phenolics present in the extracts may play a role in free radical scavenging activities of the medicinal plant.
... The plasma level of quercetin is normally in low ranges, but after consuming foods that are highly rich in it, the plasma's level of it increase to different ranges. Quercetin contains 3 rings and 5-hydroxyl group (Fig. 1) and it is naturally found in plants as a glycone or carbohydrate conjugates [6][7][8]. ...
Article
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Quercetin is a naturally occurring polyphenol flavonoid which is rich in antioxidants. It has anti-allergic functions that are known for inhibiting histamine production and pro-inflammatory mediators. Quercetin can regulate the Th1/ Th2 stability, and decrease the antigen-specific IgE antibody releasing by B cells. Quercetin has a main role in anti-inflammatory and immunomodulatory function which makes it proper for the management of different diseases. Allergic diseases are a big concern and have high health care costs. In addition, the use of current therapies such as ß2-agonists and corticosteroids has been limited for long term use due to their numerous side effects. Since the effect of quercetin on allergic diseases has been widely studied, in the current article, we review the effect of quercetin on allergic diseases, such as allergic asthma, allergic rhinitis (AR), and atopic dermatitis (AD).
... Some of the beneficial effects include cardiovascular protection, anticancer, antitumor, anti-ulcer, anti-allergy, anti-viral, anti-inflammatory activity 7 anti-diabetic [8][9][10][11] , gastroprotective effects 12 , antihypertensive 13,14 , immunomodulatory, and anti-infective. 15 Quercetin might help lower inflammation, fight allergies, support heart health, combat pain, potentially improve endurance, fight cancer, and protect skin and liver health. ...
Article
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In the absence of effective and safety therapy for COVID-19 patients, today the search for new methods of treatment is the most actual topic in medicine and pharmacy. High mortality (7.1 %) due to the development of acute respiratory distress-syndrome, which is caused by cytokine storm, dictate the need to develop a new approaches to the influence on a various pathogenetic links of the disease in the complex therapy of such patients. This review summarizes the data of experimental and clinical studies of the pharmacological properties of quercetin (mechanisms of action, pharmacological effects) and quercetin-containing drugs Quertin and Corvitin (oral and parenteral dosage forms), which are presented on the pharmaceutical market of Ukraine. The results of numerous studies indicate that quercetin has (among others) high anti-inflammatory, antiviral, membrane-stabilizing, immunomodulating and antioxidant effects. The mechanisms for the realization of these pharmacological effects are well studied and make it possible to use quercetin as a pathogenetic therapy (effect on the various pathogenesis links) in patients with coronavirus infection. This dictates the need for the conducting of appropriate clinical trials of these drugs for the prevention and treatment of coronary infection. Clinical trials results may be an innovative strategy in the treatment of COVID-19 patients.
Chapter
Nutraceutical, a combination term of nutrition and pharmaceutical, refers to a wide variety of products including food and food-derived substances (polyphenols, vitamins, etc.). Nutraceuticals are seeking substantial attention because of their ostensible safety and nutritional and therapeutic value. They offer a substantial potential to improve the human health and well-being, together with the preclusion and cure of disease. But unfortunately they have low bioavailability, poor permeability and solubility, low absorption in the gastrointestinal tract (GIT) and lack long-term stability. In order to combat all these issues, nanotechnological approach is a groundbreaking method in the field of healthcare. Nanoencapsulation of nutraceuticals using biopolymeric nanoparticles such as chitosan has manifold advantages, viz., availability, biodegradability, biocompatibility, antimicrobial property, and nontoxicity, and hence is considered safe to be used in the healthcare sector.
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Flavonoids belong to a group of polyphenolic compounds, which are classified as flavonols, flavonones, flavones, flavanols, flavan-3-ols and isoflavones according to the positions of the substitutes present on the parent molecule. Flavonoids of different classes have several pharmacological activities. Flavonoids have also been known to posses biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca +2 -ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. In view of their wide pharmacological and biological actions, they seem to be having a great therapeutic potential. Flavonoids biochemistry pharmacology therapeutic potential SUMMARY
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Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin , apigenin , chrysin , and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.
Article
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.
Article
Quercetin is the major flavonoid involved in vegetables and fruits. Quercetin is ingested from the daily diet, but in 1970s it was reported as mutagenic. Quercetin possesses a variety of pharmacological activities, and in order for further clinical application, it is important to evaluate its safety. In Ames test, quercetin is regarded as mutagenic. However, recent in vitro studies indicate that quercetin is protective against genotoxicants, and regarded as antimutagenic. Some in vivo studies including National Toxicology Program reported carcinogenic effect of quercetin in F344 rats. However, the method used in the study was unusual and the result was not reproduced. Most of the results of in vivo studies indicate that quercetin is not carcinogenic. Since 1969, the International Agency for Research on Cancer (IARC) has undertaken a program to evaluate the carcinogenic risk of chemicals. In 1999, IARC concluded that quercetin is not classified carcinogenic to humans. In the US and Europe, supplements of quercetin is commercially available, and beneficial effects of quercetin supplements were reported in clinical trials. Overall, quercetin is genotoxic to salmonella, but its safety upon human application is approved.
Article
The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice. Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6′,7′-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.
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The aglycone, or free quercetin, and total quercetin content of 75 cultivars and selections was analyzed by reverse-phase high-performance liquid chromatography. Quercetin glycosides were hydrolyzed into aglycones. Total quercetin content in yellow, pink, and red onions varied from 54 to 286 mg·kg ⁻¹ fresh weight in different onion entries grown during 1992. White onions contained trace amounts of total quercetin. Free quercetin content in all the onions was low (< 0.4 mg·kg ⁻¹ ) except in `20272-G' (12.5 mg·kg ⁻¹ fresh weight). Bulbs stored at 5, 24, and 30C and controlled atmosphere (CA) for 0,1,2,3,4, and 5 months showed a most marked change in total quercetin content at 24C compared to other treatments, with a rise in mid-storage followed by a drop. Storage at 5 and 30C also demonstrated a similar change. However, total quercetin content did not vary significantly in bulbs stored at CA for 5 months. We conclude that genetic and storage factors affect quercetin content on onions.
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Accumulating evidence supports the hypothesis that brain iron misregulation and oxidative stress (OS), resulting in reactive oxygen species (ROS) generation from H2O2 and inflammatory processes, trigger a cascade of events leading to apoptotic/necrotic cell death in neurodegenerative disorders, such as Parkinson's (PD), Alzheimer's (AD) and Huntington's diseases, and amyotrophic lateral sclerosis (ALS). Thus, novel therapeutic approaches aimed at neutralization of OS-induced neurotoxicity, support the application of ROS scavengers, transition metals (e.g. iron and copper) chelators and non-vitamin natural antioxidant polyphenols, in monotherapy, or as part of antioxidant cocktail formulation for these diseases. Both experimental and epidemiological evidence demonstrate that flavonoid polyphenols, particularly from green tea and blueberries, improve age-related cognitive decline and are neuroprotective in models of PD, AD and cerebral ischemia/reperfusion injuries. However, recent studies indicate that the radical scavenger property of green tea polyphenols is unlikely to be the sole explanation for their neuroprotective capacity and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. In this article, the currently established mechanisms involved in the beneficial health action and emerging studies concerning the putative novel molecular neuroprotective activity of green tea and its major polyphenol (-)-epigallocatechin-3-gallate (EGCG), will be reviewed and discussed.
Article
In an open, randomized, cross-over study the concentrations of 17β-estradiol and estrone in serum were measured over 192 hours in 8 ovariectomized women after a single oral dose intake of 2 mg micronized 17β-estradiol. The subjects were studied with and without grapefruit juice intake containing the three natural flavonoids, naringenin, quercetin and kaempherol, which are found as glycosides in citrus fruit. These flavonoids interact with the metabolism of drugs such as 17β-estradiol and other steroids that are extensively metabolised through the P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. After administration of grapefruit juice, peak estrone (between 2–6 hours after tablet intake) concentrations increased significantly. The AUC0–48 and AUC0–192 for estrone but not 17β-estradiol, resulting from a single administration of micronized 17β-estradiol, were significantly altered. Combined measured estrogens (i.e. 17β-estradiol and estrone) also increased significantly. The relationship between the ADCs for 17β-estradiol and estrone was not altered by juice intake indicating that a metabolic step after estrone, i.e. further A and/or D ring conversion was inhibited. This study demonstrates that grapefruit juice may alter the metabolic degradation of estrogens, and increase the bioavailable amounts of 17β-estradiol and its metabolite estrone, presumably by affecting the oxidative degradation of estrogens. This food interaction may be one factor behind the interindividual variability in 17β-estradiol, estrone and estriol serum concentrations after exogenous administration of 17β-estradiol to patients.
Article
Representative cultivars of different coloured onions were compared to determine the extent of differences in the distribution of free and total (bound and free) quercetin among different onion rings. The dry skin, outer rings, and inner rings were separated and extracted with ethanol to obtain quercetin glycosides (bound form) that were then hydrolyzed to free quercetin. Free quercetin was used as the standard for quantification by reverse phase high performance liquid chromatography (HPLC). Significant difference (P = 0.05) in total quercetin content was observed between the dry skin and inner rings (edible parts). A decrease in total quercetin content was observed from the dry skin to inner rings. The highest total quercetin concentration was observed in the dry skins of ‘Red Bone’ (30.66 g kg–1 dry weight) while ‘Contessa’ contain the least amount (0.094 g kg–1 dry weight). Total quercetin content in outer rings (1–2) in ‘Kadavan’ was high highest (345.51 mg kg–1 fresh weight); however, trace amounts were observed in ‘Contessa’. Inner rings (5–6 and 7–10) contain less total quercetin in all the cultivars. Outer rings (cataphylls) of all the cultivars except ‘Texas Grano 1015Y’ and ‘Contessa’ contain moderate amounts (2.5–16 mg kg–1 fresh weight) of free quercetin. ‘Red Bone’ skin contain the highest amount of free quercetin (20.64 g kg–1 dry weight). Quercetin distribution based on fresh and dry weight method was also evaluated.