JOURNAL OF MEDICINAL FOOD

J Med Food 18 (11) 2015, 1–8

MINI REVIEW
# Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2014.3394

Bioactives in Commonly Consumed Cereal Grains:

Implications for Oxidative Stress and Inflammation
Yoon-Mi Lee,1 Sang-Ik Han,2 Byeng Chun Song,1 and Kyung-Jin Yeum1
1
Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju, Korea.
2
National Institute of Crop Science, Rural Development Administration, Miryang, Korea.

ABSTRACT Oxidative stress and inflammation are closely linked to various chronic diseases. Thus, targeting this axis of
oxidative stress and inflammation is a particularly interesting area of study for reducing the risk of chronic diseases, including,
but not limited to, metabolic disorders, cancer, cardiovascular disease, and Alzheimer’s disease. It is well known that
antioxidants play a pivotal role in tuning this axis. In this review, we introduce five different cereal grains, which are the most
commonly consumed throughout the world and are functionally reported to have antioxidant activity: oat (Avena spp.), barley
(Hordeum spp.), rice (Oryza spp.), wheat (Triticum spp.), and rye (Secale spp.). Bioactive components of these grains, partial
grains or whole grains, have demonstrated antioxidant and anti-inflammatory activities in cells and animals. Although further
study is required to establish their efficacy for treating patients with chronic diseases, we suggest that grains, which are a great
source of antioxidants, have potential in the prevention of oxidative stress and inflammation-related chronic diseases.

KEY WORDS:  barley  chronic disease  oat  oxidative stress  reactive oxygen species  rice  rye  wheat

INTRODUCTION feature of other diseases, including diabetes, cardiovascular

disease, and Alzheimer’s disease.9–11
T he major source of reactive oxygen species (ROS),
including superoxide (O2-), hydrogen peroxide (H2O2),
and the hydroxyl radical (OH), is the mitochondrial respi-
Oxidative stress recruits and activates neutrophils and mast
cells, thereby leading to inflammation. If the inflammation
persists, it may elevate the risk of chronic diseases.12 Fur-
ratory chain, with some ROS originating from nicotinamide
thermore, oxidative stress increases the release of a variety of
adenine dinucleotide phosphate (NADPH) oxidase in
transcription factors, such as nuclear factor (NF)-jB, activator
cells.1,2 In the normal metabolism, the generated ROS have
protein-1, signal transducer, activator of transcriptions 3,
a beneficial role in the maintenance of cell life, such as
hypoxia-inducible factor-1a, NF-E2-related factor-2, p53, and
killing damaged cells and regulating cell signaling path-
others, which in turn activates inflammatory cytokines and
ways. However, ROS imbalance caused by excessive pro-
chemokines.13 Inflammation in white blood cells is related to
duction of ROS and/or deficiency of antioxidant defense
insulin resistance and type 2 diabetes, and inflammation of the
system induces oxidative stress.3,4 Therefore, the oxidative
cardiac region is related to atherosclerosis.14,15 In addition,
stress can impair cell structure, DNA, carbohydrate, protein,
neurodegenerative diseases are associated with inflammation
and lipid and contribute to various chronic diseases, in-
in the brain.16 It is well established that inflammation pro-
cluding diabetes, cancer, cardiovascular disease, and Alz-
motes tumorigenesis by infiltration of immune cells.17 In-
heimer’s disease.5,6
flammatory bowel diseases, which can be classified as
Notably, oxidative stress participates in DNA damage,
ulcerative colitis and Crohn’s disease, are largely linked to
which leads to DNA lesions, mutations, genetic alteration,
colon tumorigenesis.18,19 Thus, targeting inflammation is very
and drug resistance in carcinogenesis.7 A possible under-
important for understanding the etiology of chronic diseases.
lying mechanism of increased ROS in cancer presumably
Collectively, to define the axis among oxidative stress, in-
arises from oncogenic signals, which results in dysfunction
flammation and chronic diseases might provide an effective
of the metabolic system.8 In addition, many studies have
strategy in the prevention and therapy of chronic diseases.
been reported that high generation of ROS is a common
Antioxidants can be divided into two groups: enzymatic
and nonenzymatic antioxidants. The main enzymatic antiox-
Manuscript received 20 November 2014. Revision accepted 11 May 2015. idants are superoxide dismutases (SODs), catalase (CAT), and
glutathione peroxidase (GPx). SODs catalyze the superoxide
Address correspondence to: Kyung-Jin Yeum, PhD, Division of Food Bioscience, College
of Biomedical and Health Sciences, Konkuk University, 268 Chungwondaero, Chungju
anion into H2O2 and oxygen, CAT catalyzes hydrogen per-
380-701, Republic of Korea, E-mail: kyeum@kku.ac.kr oxide to water, and GPx reduces hydroperoxides.20,21

1
2 LEE ET AL.
In contrast, many foods contain nonenzymatic antioxi-
dants, including phenolic compounds, flavonoids, vitamin
C, vitamin E, thiol antioxidants, and many others.22 Fur-
thermore, it has been reported that dietary antioxidants have
been used for the prevention and therapy in various chronic
diseases.23 Quercetin (abundant in onion) was effective in
reducing the risk of cardiovascular diseases and cancer.24,25
Resveratrol (abundant in wine) has been shown to reduce the
risk of cardiovascular diseases and protect against Alzhei-
mer’s disease by several mechanisms.26,27 Theaflavins and
thearubigins (abundant in black tea) were used as anticancer
agents in prostate cancer cells.28,29 Other food extracts and
bioactive components continue to be studied for their
functional activities30,31 Food bioactive compounds are es-
pecially attractive for the prevention of chronic diseases
because they have much lower side effects than many che-
mical drugs.
Among foods, grains have received less attention for re-
ducing the incidence of chronic diseases than fruits and
other plants. However, many research groups have demon-
strated the antioxidant capacity of grains and the defensive
roles in oxidative stress and inflammation in vitro and
in vivo.32 Increasing evidence suggests that whole grains,
partial grains, or bioactive components of grain consump-
tion may protect against cardiovascular diseases, hyperten-
sion, metabolic disorders, and specific cancer.33–35 Above
all, grains are inexpensive, accessible, and safe.
In this review, we discuss five different cereal grains, oat,
barley, rice, wheat, and rye, which are commonly cultivated
and consumed worldwide. The main bioactive components
in oats are avenanthramides and b-glucan. Benzoic and
cinnamic acid derivatives are rich in barley, anthocyanins in
pigmented rice, ferulic acid in wheat, and alkylresorcinols in
rye.34 In this study, we focus on their functional antioxidant
capacities and anti-inflammatory activities, which have the
potential to prevent/delay chronic diseases.
BASIC UNDERSTANDING OF INFLAMMATION
Inflammation is the main response to harmful stimuli such
as pathogens, mechanical stress, wounds, and unfavorable
diets.36 In the first process of inflammation, described as
innate immunity, many inflammatory factors appear in
damaged sites to protect the host. However, if the inflam-
matory response is prolonged, expressed as adaptive im-
munity, it may lead to a variety of chronic diseases and
further production of oxidative stress.37
Figure 1 illustrates inflammation as an aspect of cell sig-
naling. Upon initiating the inflammatory response, it acti-
vates signal transduction cascades such as mitogen-activated
protein kinase pathways by phosphorylation, extracellular
signal-regulated kinases, c-jun N-terminal kinase, and p38
kinases.38,39 Although a variety of substrates have been
identified, NF-jB is regarded as the main transcription factor
controlling inflammation responses. NF-jB is the hetero-
dimer of p65 and p50, which is generally sequestered by the
inhibitory jB (IjB)-a protein in the cytoplasm.40 After ex-
tracellular stimuli, NF-jB becomes dissociated, form IjB-a,
and is translocated to the nucleus. The remaining IjB-a in
the cytoplasm goes to the proteasome and is degraded, while
active NF-jB binds to its DNA-binding domain of downstream
genes, thereby promoting activation of proinflammatory cyto-
kines, including interleukin (IL)-1, IL-6, tumor necrosis factor
(TNF), chemokines, including IL-8, CXC chemokine receptor
4, inducible nitric oxide synthase, and cyclooxygenase-2.41–43
Following these steps in the cells, C-reactive proteins (CRP) are
FIG. 1. Overview of inflammation in
cells. Upon initiating extracellular stimuli,
MAPKs such as ERK, JNK, and p38 ki-
nase were phosphorylated and activate
transcription factor NF-jB, which is a
heterodimer of p65, and p50 generally
sequestered by IjB-a under normal con-
dition. The nucleus NF-jB promotes to
induce inflammation-related genes and,
thereby, induces prolonged inflammation.
DBD, DNA-binding domain; ERK, ex-
tracellular signal-regulated kinases; IjB-
a, inhibitory jB-a; JNK, c-jun N-terminal
kinases; MAPK, mitogen-activated pro-
tein kinase; NF, nuclear factor.
 THE NEW INSIGHT ON CEREAL GRAINS AS FUNCTIONAL FOODS
produced in the liver and used as one of the important in-
flammation markers.44
The first aim of inflammation is to relive the unfavorable
condition, whereas prolonged inflammation increases the
possibility of pathogenesis of chronic diseases by triggering
inflammation cascades. Thus, modulation of chronic in-
flammation could be an attractive therapeutic target.45
ASSESSMENT OF OXIDATIVE
STRESS BIOMARKERS
Various analytical methods have been introduced to es-
timate antioxidant activities of food in vitro. For example,
2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20 -azino-bis(3-
ethylbenzothiazoline-6-sulfonic acid) (ABTS) are com-
monly used free radicals for estimating food antioxidant
capacities and to investigate whether food extracts attenuate
free radicals. Ferric-reducing ability power and oxygen
radical absorbance capacity (ORAC) are also used as in
vitro assessments of antioxidant capacity.46–49
Intracellular ROS can be determined by 20 ,70 -
dichlorofluorescin-diacetate (DCF-DA). DCF-DA is
permeable to cells and fluoresce with oxidation. 50 How-
ever, it is difficult to detect ROS by DCF-DA in tissue,
serum, and urine. When excessive ROS are present in the
body, many macromolecules such as DNA, lipid, and
protein are the main targets of damage. 51 Therefore, by-
products of oxidative-damaged macromolecules can be
measured. The hydroxyl radical induces DNA damage
shown as DNA double-strand breaks, which can be
detected by 8-hydroxydeoxyguanosine (8-OHdG) and
c-H2AX.52,53 Lipid peroxidation is elevated in the oxi-
dative stress environment, and polyunsaturated fatty ac-
ids are degraded into malonialdehyde ( MDA), which can
be determined by reaction with thiobarbituric acid. Low-
density lipoprotein (LDL) is also oxidized by ROS, known as
oxidized LDL (oxLDL), and 4-hydroxy-2-nonenal (4-HNE)
is increased.54 Protein damage can be detected by elevations
3
of protein carbonyl as well as protein modifications such as S-
glutathionylation and nitrotyrosine.55 In addition, oxidized
polyunsaturated fatty acids and sugars produce reactive car-
bonyl species (RCS). RCS induce advanced lipoxidation end
products/advanced glycosylation end products (AGEs) by
reacting with protein. AGEs interact with their receptors
(RAGE), which promote cellular and organ dysfunction and
inflammation.56
Since ROS and RCS are regarded as major integrators of
chronic diseases, assessment of oxidative stress is a very
important tool for the prognosis in patients with oxidative
damage-associated diseases. Figure 2 presents various in
vitro and ex vivo analytical methods reported for measuring
oxidative stress. The quenching of ROS and RCS can be
attractive approaches for the prevention of oxidative stress-
associated diseases.
THE ROLE OF OAT (AVENA SPP.)
IN OXIDATIVE STRESS AND INFLAMMATION
Oat has been consumed as oatmeal and rolled oats for hu-
mans and as feed for livestock. Because of its great health
benefits, many scientists were interested in the research of oat
instead of the other grains for a decade. Oats contain antiox-
idant components consisting of avenanthramides, tocopherols,
tocotrienols, b-glucan, and phenolic compounds.57–59 In par-
ticular, avenanthramide is a polyphenol compound, which is
abundant in oats, and its antioxidant and anti-inflammatory
activities have been reported. Avenanthramides blocked
NF-jB activities and consequently decreased inflammation-
related cytokine production.60 Oat b-glucan is associated with
reduced risk of cardiovascular diseases.61
In a recent study, seven cultivars of oats were examined by
ORAC assay and anti-inflammatory activity. Oats have high
antioxidant activities, as evaluated by ORAC activity. Among
seven oat cultivars, CDC Dancers and CDC Deiter decreased
NF-jB activity, which is stimulated by TNF-a; certain cultivars
of oat could be promising for anti-inflammatory properties.62
FIG. 2. Biomarkers of oxidative
stress. Oxidative stress can be measured
by various methods, in vitro, in cells
and in animals. ABTS, 2,20 -azino-bis
(3-ethylbenzothiazoline-6-sulfonic acid);
AGE, advanced glycosylation end product;
DCF-DA,20 ,70 -dichlorofluorescin-diacetate;
DPPH, 2,2-diphenyl-1-picrylhydrazyl;
FRAP, ferric-reducing ability power;
4-HNE, 4-hydroxy-2-nonenal; MDA,
malonialdehyde; 8-OHdG, 8-
hydroxydeoxyguanosine; ORAC, oxy-
gen radical absorbance capacity; oxLDL,
oxidized low-density lipoprotein.
4 LEE ET AL.

In addition, oats potently relieve inflammatory disease. Celiac THE ROLE OF RICE (ORYZA SPP.)
disease is a dietary gluten-induced autoimmune disease.63 IN OXIDATIVE STRESS AND INFLAMMATION
Because oats are useful in gluten-free diets, it is interesting that
Since rice is one of the most consumed grains worldwide, it
it attenuates in vitro celiac disease environments by inhibiting
is crucial to study the effect of rice on health benefits. Rice has
early inflammation response.64
various antioxidant components, including phenolic com-
One of the severe problems in diabetic patients is the
pounds, c-oryzanol, carotenoids, tocopherols, and toco-
comorbidities such as blindness at an early age.65 In an
trienols.73 Besides, pericarps of red and black rice were known
animal study, diabetic rats fed oats, were observed to have
to be much higher in antioxidant than other light-colored rice
relieved symptoms of diabetic retinopathy by reducing ox-
varieties.74 In particular, black rice with giant germ has been
idative stress and inflammation.66 Data showed that anti-
reported to contain high amounts of fat-soluble antioxidant
oxidant enzymes were elevated, whereas oxidative stress
materials, such as carotenoids (lutein, trans-b-carotene), vi-
markers and activated NF-jB protein levels were reduced.
tamin E (a, c-tocopherol, a, c-tocotrienols), and c-oryzanol.75
Another comorbidity in diabetic patients is kidney damage,
In addition, various studies have shown that ROS were de-
known as nephropathy. Kidney damage, such as segmental
creased in anthocyanin extracted from black rice-treated
glomerulosclerosis and tubule vascular degeneration, was
cells.76 Furthermore, black rice was reported to have signifi-
attenuated in oat-fed experimental diabetic rats as well as
cant antioxidant activities and anti-inflammatory effects and,
reduced AGEs and NF-jB levels.67
thereby, attenuated atherosclerosis in animals.77 Likewise,
In a clinical study, an oat-rich diet had no effect on glu-
antioxidant and anti-inflammatory effects were observed in
cose and insulin levels, but did lower cholesterol levels
patients with coronary heart disease, who consumed the black
compared to standard diets. Inflammation and oxidative
rice pigment fraction for 6 months. Supplementation of an-
stress in patients with type 2 diabetes were not reduced after
thocyanins of black rice pigment fraction induced plasma total
ingestion of oat-rich diets.68 The effect of oat remains un-
antioxidant capacity and reduced inflammation markers such
certain in patients with chronic diseases.
as high-sensitive CRP in human.78

THE ROLE OF BARLEY (HORDEUM SPP.) THE ROLE OF WHEAT (TRITICUM SPP.)
IN OXIDATIVE STRESS AND INFLAMMATION IN OXIDATIVE STRESS AND INFLAMMATION
Barley is a crop used for humans and livestock and has Wheat is the most globally consumed grain. While much
been recently drawing attention as a medicinal grain. For a research has focused on gluten of wheat-induced allergy and
decade, much research has shown the biological activities of inflammation,79 aleurone is the most important component of
barley. There are antioxidant components such as phenolics, wheat, which also has high amounts of phenolic compounds
flavonols, carotenoids, and tocopherols in barley.69 Ac- such as ferulic acid. Interestingly, it has much higher antioxidant
cording to a recent study, barley has been demonstrated to capacity than other components such as bran and flour.80 The
function as an antioxidant and anti-inflammatory in vitro
and in vivo. Chronic ingestion of alcohol induces excessive
production of ROS and leads to liver damage. However,
fermented barley extract alleviated alanine aminotransferase
and aspartate aminotransferase levels by improving anti-
oxidant activities in vivo.70 In addition, the same group has
reported that fermented barley extract suppressed IL-1, IL-
6, and TNF-a in plasma of lipopolysaccharide (LPS)-
induced inflammation in rats, thereby suggesting that barley
extract has anti-inflammatory activities. The underlying
mechanism of the anti-inflammatory effects of fermented
barley extract was related to upregulation of antioxidant
enzyme activities and downregulation of oxidative stress
markers such as nitric oxide and 8-OHdG.71
In another recent study, methanol extract of barley has
been fractioned, and it was found that four fractions reduced
inflammatory cascades such as the NF-jB-binding activity
and cytokine levels in LPS-stimulated macrophage cells.
Furthermore, oral treatment with a barley extract fraction
increased survival rate up to 80% compared to the vehicle-
treated group in LPS-injected mice.72 They have shown that
its bioactive material was derivative of benzoic acid, cin-
namic acid, and fatty acids. From these findings, barley
could be used for preventing inflammatory disease and FIG. 3. Grains that protect against oxidative stress, inflammation,
inflammation-related diseases. and chronic diseases.
 THE NEW INSIGHT ON CEREAL GRAINS AS FUNCTIONAL FOODS 5

Table 1. Major Bioactive Components of Grains and Their Functional Activities

Grains Major bioactive compounds Functional activities References

83
Oat Avenanthramides Antioxidant activity
60
Anti-inflammatory activity by decreasing NF-jB activity
84
Antiproliferative effects in colon cancer cells
61
b-Glucan Reduced CHD risk by lowering cholesterol levels
85,86
Barley Benzoic, cinnamic Antioxidant activity by scavenging free radical and inhibiting
acid derivatives human LDL oxidation
72
Reduced acute inflammatory responses
73
Rice (Pigmented) Anthocyanins Antioxidant activity
76
Anti-inflammatory activity by suppressing iNOS expression
78
Reduced CHD risk in patients
87
Wheat Ferulic acid Antioxidant activity by scavenging free radical
88
Anti-inflammatory activity by decreasing inflammatory cytokines
Antiproliferative activity in colon cancer cells
89
Rye Alkylresorcinols Antioxidant activity by scavenging free radical
90
Antioxidant activity by inhibiting production of oxLDL
91
Protection of cell viability from prooxidant
92
Anti-inflammatory effect on colitis model in rat

CHD, chronic heart disease; iNOS, inducible nitric oxide synthase; LDL, low-density lipoprotein; NF, nuclear factor; oxLDL, oxidized LDL.

aleurone of wheat exerted anti-inflammatory effects in LPS-
stimulated macrophages and inhibited TNF-a production.81 In
addition, wheat aleurone had great antioxidant and anti-
inflammatory properties in healthy humans. The results showed
that aleurone-enriched diets attenuated the inflammation marker
CRP, but there was no difference in endothelial function.82
THE ROLE OF RYE (SECALE SPP.)
IN OXIDATIVE STRESS AND INFLAMMATION
Rye is mainly cultivated in Europe and has common
features with wheat and barley. It has been processed as
various foods such as bread and whiskey. Rye is rich in
alkylresorcinols, which are phenolic lipids and can be used
as a marker of whole grain intake due to its existence in the
outer layers of grain.88 The antioxidant activity of the al-
kylresorcinols had been well studied. The alkylresorcinols
of whole grain rye are reported to scavenge DPPH radicals89
and inhibit production of oxLDL in vitro.90 Other studies
observed that the outermost fraction had more abundant
alkylresorcinols than the inner fraction and their strong
antioxidant activity protecting cell viability.91 In addition,
rye bran is reported to have anti-inflammatory effects on the
colitis model in rat.92

FIG. 4. Chemical structures of major

bioactive components in grains.
6 LEE ET AL.
SUMMARY
Oxidative stress, inflammation, and chronic diseases are
closely interrelated. Thus, antioxidant properties of grains
have beneficial effects for the regulation of inflammation
and chronic diseases. In this study, we reviewed the anti-
oxidant properties, anti-inflammatory effects, and the pos-
sibility of protection against various chronic diseases in five
different cereal grains: oat, barley, rice, wheat, and rye
(Fig. 3). Based on previous research, it is well established
that there are positive effects of grains (whole grains, partial
grains, or bioactive components of grains) in cells, animals,
and humans. Major bioactive components of grains are lis-
ted in Table 1, and their structures are presented in Figure 4.
Although further study is required with respect to duration
and amount of consumption, grains could be a promising
new dietary strategy for the prevention of oxidative stress-
associated chronic diseases.
ACKNOWLEDGMENT
Supported, in part, by the Rural Development Adminis-
tration (PJ010059), Republic of Korea.
AUTHOR DISCLOSURE STATEMENT
No competing financial interests exist.
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