Antioxidant Activities of Flavonoids

Department of Environmental and Molecular Toxicology

Oregon State University
Dr. Donald R. Buhler
Dr. Cristobal Miranda
Summary: Flavonoids are compounds found in fruits, vegetables,
and certain beverages that have diverse beneficial biochemical and
antioxidant effects. Their dietary intake is quite high compared to
other dietary antioxidants like vitamins C and E. The antioxidant
activity of flavonoids depends on their molecular structure, and
structural characteristics of certain flavonoids found in hops and
beer confer surprisingly potent antioxidant activity exceeding that of
red wine, tea, or soy.
Flavonoids are polyphenolic compounds that are ubiquitous in
nature and are categorized, according to chemical structure, into
flavonols, flavones, flavanones, isoflavones, catechins,
anthocyanidins and chalcones. Over 4,000 flavonoids have been
identified, many of which occur in fruits, vegetables and beverages
(tea, coffee, beer, wine and fruit drinks). The flavonoids have
aroused considerable interest recently because of their potential
beneficial effects on human health-they have been reported to have

antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor and

antioxidant activities.
Antioxidants are compounds that protect cells against the damaging
effects of reactive oxygen species, such as singlet oxygen,
superoxide, peroxyl radicals, hydroxyl radicals and peroxynitrite. An
imbalance between antioxidants and reactive oxygen species results
in oxidative stress, leading to cellular damage. Oxidative stress has
been linked to cancer, aging, atherosclerosis, ischemic injury,
inflammation and neurodegenerative diseases (Parkinson's and
Alzheimer's). Flavonoids may help provide protection against these
diseases by contributing, along with antioxidant vitamins and
enzymes, to the total antioxidant defense system of the human
body. Epidemiological studies have shown that flavonoid intake is
inversely related to mortality from coronary heart disease and to
the incidence of heart attacks.
The recognized dietary antioxidants are vitamin C, vitamin E,
selenium, and carotenoids. However, recent studies have
demonstrated that flavonoids found in fruits and vegetables may
also act as antioxidants. Like alpha-tocopherol (vitamin E),
flavonoids contain chemical structural elements that may be
responsible for their antioxidant activities. A recent study by Dr. van
Acker and his colleagues in the Netherlands suggests that flavonoids
can replace vitamin E as chain-breaking anti- oxidants in liver
microsomal membranes. The contribution of flavonoids to the
antioxidant defense system may be substantial considering that the
total daily intake of flavonoids can range from 50 to 800 mg. This
intake is high compared to the average daily intake of other dietary
antioxidants like vitamin C (70 mg), vitamin E (7-10 mg) or
carotenoids (2-3 mg). Flavonoid intake depends upon the
consumption of fruits, vegetables, and certain beverages, such as
red wine, tea, and beer. The high consumption of tea and wine may
be most influential on total flavonoid intake in certain groups of
people.
The oxidation of low-density lipoprotein (LDL) has been recognized
to play an important role in atherosclerosis. Immune system cells
called macrophages recognize and engulf oxidized LDL, a process

that leads to the formation of atherosclerotic plaques in the arterial

wall. LDL oxidation can be induced by macrophages and can also be
catalyzed by metal ions like copper. Several studies have shown that
certain flavonoids can protect LDL from being oxidized by these two
mechanisms.
Antioxidant flavonoids
(listed in order of decreasing potency)

Quercetin (a flavonol in vegetables, fruit skins, onions)

Xanthohumol (a prenylated chalcone in hops and beer)

Isoxanthohumol (a prenylated flavanone in hops and beer)

Genistein (an isoflavone in soy)

Pro-oxidant flavonoids

Chalconaringenin (a non-prenylated chalcone in citrus

fruits)

Naringenin (a non-prenylated flavanone in citrus fruits)

The capacity of flavonoids to act as antioxidants depends upon their

molecular structure. The position of hydroxyl groups and other
features in the chemical structure of flavonoids are important for
their antioxidant and free radical scavenging activities. Quercetin,
the most abundant dietary flavonol, is a potent antioxidant because
it has all the right structural features for free radical scavenging
activity.
Recently, chalcone and flavanone flavonoids with prenyl or geranyl
side chains have been identified in hops and beer by Dr. Fred
Stevens and Dr. Max Deinzer at Oregon State University. Hops are
used in beer for flavor. Xanthohumol (a chalcone) and
isoxanthohumol and 6-prenylnaringenin (flavanones) are the major
prenyl-flavonoids found in beer. Although the antioxidant activities
of these compounds have not been studied, these flavonoids may be

responsible for the antioxidant activity of lager beer, which is higher

than that of green tea, red wine, or grape juice as reported earlier
by Dr. Joe A. Vinson from the University of Scranton in
Pennsylvania. Xanthohumol is found only in beer but in small
concentrations.
To assess the antioxidant activity of the prenylated flavonoids, we-in
collaboration with LPI researchers-evaluated the capacity of these
flavonoids to inhibit the oxidation of LDL by copper. The antioxidant
properties of the prenylflavonoids were compared to those of
quercetin (a flavonol), genistein (the major isoflavone in soy),
chalconaringenin (a non-prenylated chalcone), naringenin (a nonprenylated flavanone), and vitamin E. The possible interaction of
xanthohumol, the major prenylchalcone in beer, with vitamin E to
inhibit LDL oxidation induced by copper was also examined.
Our results showed that the prenylchalcones and prenylflavones are
effective in preventing LDL oxidation initiated by copper and that
the prenylchalcones generally have greater antioxidant activity than
the prenylflavanones. Xanthohumol, the major prenylchalcone in
hops and beer, is a more powerful antioxidant than vitamin E or
genistein. However, xanthohumol was less potent than quercetin.
The potency of xanthohumol as an antioxidant is markedly
increased when combined with an equivalent amount of vitamin E.
As reported in the Journal of Agricultural and Food Chemistry, we
also found that the prenyl group plays an important role in the
antioxidant activity of certain flavonoids. A flavonoid chalcone
(chalconaringenin) and a flavanone (naringenin) with no prenyl
groups act as pro-oxidants, i.e. they promote rather than limit the
oxidation of LDL by copper. However, adding a prenyl group to these
flavonoid molecules counteracted their pro-oxidant activities.
Our work reveals that there are unique flavonoids in hops and beer
that may be potentially useful in the preventionof human disease
attributed to free radical damage. The observation that prenyl
groups are important in conferring antioxidant activity to certain
flavonoids may lead to the discovery or synthesis of novel
prenylated flavonoids as preventive or therapeutic agents against
human diseases associated with free radicals. Our encouraging

results with xanthohumol suggest that this prenylchalcone should be

further studied for its antioxidant action and protective effects
against free radical damage in animals and humans. Preliminary
studies have shown that xanthohumol is absorbed from the
digestive tract in rats, and more studies are needed to evaluate the
bioavailability of these interesting flavonoids in people.
Further studies are also needed to establish the safety of
xanthohumol or other flavonoids for use as dietary supplements
since high doses of these compounds may produce adverse effects
in humans, according to recent findings by Dr. Martyn Smith,
professor of toxicology, University of California at Berkeley.
For additional information on flavonoids, see the Linus Pauling
Institute's Micronutrient Information Center.
Last updated November, 2000