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Rice bran constituents: immunomodulatory and

therapeutic activities
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Cite this: DOI: 10.1039/c6fo01763k

Ho-Young Park,a,b Kwang-Won Leeb and Hee-Don Choi*c

Received 7th December 2016,
Accepted 9th February 2017
DOI: 10.1039/c6fo01763k
rsc.li/food-function
Rice bran, one of the most abundant and valuable byproducts produced during the rice milling process, is
of steadily growing interest in recent years due to its potential health benefits. Evidence is rapidly accumu-
lating for the beneficial effects of nutraceuticals. However, the potential benefits of rice bran are found
in several of its bioactive ingredients including oils, polysaccharides, proteins, and micronutrients. In
addition, a significant advantage of rice bran is that it contains more than 100 antioxidants and several
categories of bioactive phytonutrients, such as polyphenols, phytosterols, tocotrienols, γ-oryzanol,
B vitamins, minerals, and trace minerals. As an immunomodulator, rice bran has beneficial constituents
such as polysaccharides, proteins, and oils. Numerous studies also reported that potent antioxidants in
rice bran included immune system enhancing compounds, such as phytosterols, polysaccharides,
minerals and trace minerals including magnesium, selenium, zinc, vitamin E, omega-3 fatty acids and
several other phytonutrients. We believe that this review will be a valuable resource for more studies on
rice barn as a dietary source.

1. Introduction Dehusking of raw rice results in brown rice, which is

Rice, one of the major cereals, originates from the seed of the
monocotyledonous plant Oryza sativa L. (Asian rice) or Oryza
glaberrima Steud. (African rice). It is grown in more than 100
countries of the world and is used almost exclusively as a food
for humans.1 The global rice production is 741 million tons
and this huge amount of production resulted in more than
70 million tons of rice bran in 2014.2 It has been reported that
more than 2 billion people obtain 75% of their daily calorie
intake from rice in Asian countries.3 Before consumption,
almost all rice is milled and approximately 7% of rice bran is
produced as a byproduct during the rice milling process, a
crucial step in post-production similar to grains (Fig. 1). Rice
bran is usually not consumed as part of an ordinary diet
because it does not masticate well and because of possible
hull contamination;4 therefore, most rice bran is used directly
as an ingredient in animal feed. The objective of a rice milling
process is to remove the husk and the bran layers from paddy
rice, and to produce an edible white kernel (endosperm) that
is sufficiently milled and free of impurities.
a
Division of Functional Food Research, Korea Food Research Institute,
Gyeonggi 463-746, South Korea
b
Department of Food Bioscience & Technology, Korea University, Seoul 136-713,
South Korea
c
Division of Strategic Food Research, Korea Food Research Institute,
Gyeonggi 463-746, South Korea. E-mail: chdon@kfri.re.kr; Fax: +82-31-709-9876
covered by bran layers (5–10% of brown rice).5 The rice by-
product, rice bran and hulls contain a large number of bio-
active compounds, as well as the embryo. Rice bran, a part of
the rice kernel that contains aleurone, nucellus, seed coat, and
pericarp fractions, is a byproduct of rice milling. Here, we
present an overview of selected recent studies on the distri-
bution of these compounds among the rice-derived products.
Rice bran serves as a source of numerous individual bio-
active compounds such as oils, fibers, proteins, and minerals,
many of which have been widely studied and shown to exhibit
beneficial effects in vitro and in vivo. In addition, the dietary
supplements contained in rice bran extracts can play an impor-
tant role in the existing food crises besides their associated
health claims.6 This accounts for the extensive literature on the
multifaceted aspects of ground rice bran, extract, oils, and hulls
as indicated by over 15 000 publications listed in the Scopus
database including numerous reviews. This overview therefore
focuses on identifying and interpreting the present knowledge
on the compositional chemistry and biological benefits includ-
ing the immunomodulatory, antioxidative, antiallergenic, anti-
carcinogenic, anticholesterol, and antidiabetic activities of rice
bran derivatives in cells, animals, and humans.
2. Rice bran constituents
Bran is a brown rough layer present between the endosperm
and the outer husk of the paddy (Fig. 1). Rice bran is an

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Fig. 1 An anatomy of a rice kernel. The inedible hull is the only part that is removed to produce brown rice, preserving the bran, the embryo, and
the endosperm. The hull (husk) is the outer most layer that protects the inner seed of the grain. Once the hull has been removed, brown rice in left.
Brown rice appears brown because of the bran outer layer. This bran outer layer contains starch, dietary fibers, oils, proteins, vitamins, and dietary
minerals. The bran, bran residue and germ are removed through a milling process to produce white rice.

underutilized byproduct despite being a nutrient-dense Table 1 Amino acid composition of rice bran protein using HPLC
product and stabilized by prompt heat treatment after analysis
milling.7 It can be used as an ingredient in food processing
Amino acids Compositiona (%)
because of the protection it offers against the deterioration of
high-content nutrients by rancid oils. Rice bran contains Essential amino acids Lysine 0.57
various valuable nutrients such as lipids, fibers, proteins, and Methionine 0.21
Threonine 0.46
minerals, and has been utilized by the baking, confectionary, Tryptophan 0.07
and food-processing industries because of its high nutrition Histidine 0.31
value.8 Leucine 0.83
Isoleucine 0.31
A nutrient analysis of rice bran and its derivatives indicated Valine 0.59
that oils (20–29%), carbohydrates (20–27%), and proteins Phenylalanine 0.53
(10–15%) are the three major components,9 in addition to Non-essential amino acids Tyrosine 0.38
Cysteine 0.27
several valuable phytonutrients, antioxidants, and minerals. Arginine 0.93
Rice bran is also rich in B-complex vitamins.10 In addition, Serine 0.55
it has been reported that rice bran contains high levels of Alanine 0.70
Glutamic acid 1.58
phytochemicals, such as γ-oryzanol, γ-aminobutyric acid, Aspartic acid 1.09
tocotrienols, tocopherols, carotenoids, phytic acid, phenolic Glycine 0.63
compounds, octacosanol, and squalene.1 a
Data from Juliano (1985)11.
2.1. Proteins
The rice bran protein (RBP) is complete in all of the essential
amino acids (Table 1) for human nutrition, which includes protein efficiency ratio (PER) of 1.6–1.9 and digestibility of
lysine, methionine, threonine, tryptophan, histidine, leucine, 70–75%, thus RBP has an even higher PER of 2.0–2.5 (similar
isoleucine, valine, and phenylalanine.11–13 Other amino acids in to casein from milk, PER 2.5) due to the removal of fiber and
RBP, such as cysteine and tyrosine, are non-essential amino phytic acid.14,18 Chromatographic analysis shows that the
acids, but are synthesized from methionine and phenylalanine, molecular weight distribution of albumin, globulin, prolamin
respectively, and can act as substitutes for some amino acids.14 and glutelin in rice protein isolates is 10–200, 16–130, 19–90,
Several studies have been conducted on the preparation of and 7–12.6 kDa, respectively.19
RBP from full-fat and defatted rice bran using an alkaline RBP has garnered interest in the food industry because of
extraction method, which is the most common method used its valuable components and nutraceutical properties. RBP is
because the reagents required for the process are easily avail- well known as one of the lowest allergy generating proteins
able.15 Because one of the major components in rice bran is used in the production of dietary supplements and infant
starch, hydrolyzing enzymes such as α-amylase, glucoamylase, formulations.20 It has been reported that rice bran-derived
and pullulanase are often used to enrich the protein concen- proteins and peptides protect against disease and function as
tration in rice bran by removing the starch.16 Efficient extrac- nutraceutical agents. Most of the biofunctional peptides pre-
tion methods such as the enzymatic method,12 and the combi- pared from rice bran were prepared by enzymatic hydrolysis.21
nation of physical treatment with enzymes16 for RBP result in RBP and derivatives have been shown to possess antioxidant
a high protein concentrate and extraction yield and a low fiber activities,22 immunomodulatory activities,23 antihypertensive
and ash concentrate.17 Rice bran has been reported to have a properties,24 cancer growth inhibition properties,25 angiotensin-

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converting enzyme (ACE) activities,26 and inflammatory cyto-
kine signaling properties.27
In addition, rice bran protein enhanced the physico-
chemical stability of food matrices like oil/water emulsion,28
viscoelastic properties,29 enzymatic browning inhibition,30 and
cake properties.31
2.2. Oils
Vegetable oils are composed of several bioactive compounds,
such as polyphenols and tocopherols.32 Rice bran oil (RBO) is
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liquid chromatography.38 Moreover, the higher oryzanol levels
in RBO may contribute to the higher free fatty acid (FFA)
values in this oil.
Dietary supplementation with RBO has been reported in
human studies to reduce total cholesterol (TC), low-density
lipoprotein cholesterol (LDL-C), and triglycerides (TG) and to
increase high-density lipoprotein cholesterol (HDL-C) levels in
the blood (Table 2). RBO has also been demonstrated to
prevent colon cancer,44 diabetic nephropathy,45 and extra-
pyramidal symptoms.8 As a dietary supplement, the commer-

an important derivative of rice. Rice bran has more than 20%
of lipid and that lipid is extracted to obtain oils, another
important product of rice bran. RBO has been demonstrated in
numerous clinical studies to function in regulating the lipid
metabolism,33,34 and is used in cooking and salad dressing.
RBO is renowned for its very high smoke point of 254 °C
(490 °F) and delicate flavor, making it suitable for high-tempera-
ture cooking such as deep frying.9 Most of the earlier studies on
rice bran focused on the development of a defatting procedure
since raw rice bran does not have a stable shelf life. However,
after the 1970s, food scientists developed an efficient method
for RBO extraction and evaluated the health benefits of RBO.
RBO is not only a nutritious vegetable oil, but is also a valu-
able oil with many health benefits.35 RBO has a balanced fatty
acid profile in terms of saturated, monounsaturated, and poly-
unsaturated fatty acids and contains valuable components
such as γ-oryzanol, γ-aminobutyric acid, tocopherols, and
tocotrienols, which are known for their health promoting
properties.36 The fatty acid composition of RBO is moderately
high in monounsaturated fat (42%) and polyunsaturated fat
(40%; 38% omega-6 fatty acids and 2% omega-3 fatty acids),
and low in saturated fat (18%).37 RBO also has a higher un-
saponifiable fraction (4%) than any other vegetable-extracted
oil. The fatty acid composition of RBO is in the range of
16.5–21.8% palmitic, 1.8–2.9% stearic, 35–41% oleic,
34.4–42.6% linoleic, 0.3–2.9% linolenic, 0.7–1.1% arachidic,
and 0.7% behenic acids that have been analyzed using gas-
cial RBO product offers potential health benefits for hyper-
cholesterolemia and diabetes.
2.3. Carbohydrates
The carbohydrates in rice bran are found in different forms
and are composed of polysaccharides, oligosaccharides,
celluloses, hemicelluloses, starch, and some sugars.37 The
water-soluble polysaccharides of rice bran include oligo-
saccharides, hemicelluloses, and non-starchy polysaccharides
along with water-soluble phytochemicals.46 Plant polysaccharides
have a specific conformational structure, which induces
the production of anti-inflammatory cytokines and inhibits
pro-inflammatory cytokines.47,48 They also act as immuno-
modulators through innate and cell-mediated immunity and
through interactions with T cells, monocytes, macrophages,
and polymorphonuclear lymphocytes.49
Rice bran fiber (RBF) consists of both soluble and insoluble
fibers.50 It has been reported that RBF possesses a water-
binding capacity of 4.89 mL g−1 and a fat-binding capacity
of 4.54 mL g−1,51 and shows more water- and fat-binding
capacities after enzymatic preparation than chemical prepa-
ration.52 Dietary fibers usually alter the rheological properties
of the dough and, therefore, the quality and sensory properties
of the end product.
Numerous clinical studies revealed that insoluble RBF not
only normalizes bowel movement, but can also help in digestive
conditions such as irritable bowel syndrome.53 Rice bran fiber

Table 2 Rice bran oil and its valuable components’ effect on lipid metabolism in clinical studies

Number
Population (experimental/ Duration
(serum TC level, mmol L−1) control) Study design Source Dose/day of study Effects Ref.

Moderately 14/17 Randomized, double-blind, Full-fat rice bran 84 g 6 weeks ↓Serum TC 39

hypercholesterolemic (5.9–8.0) non-cross-over and LDL-C
Healthy (5.33 ± 0.11) 14/14 Randomized, double-blind, Rice bran oil 1/3 of the total 10 weeks ↓LDL-C 33
crossover dietary fat
Mildly hypercholesterolaemic 40/40 Randomised, double-blind, Rice bran oil 20 g 12 weeks ↓TC 34
(≥5) cross-over
Hypercholesterolemic (>6.5) 18/18 Randomized, Tocotrienol-rich 100 mg 35 days ↓TC, LDL-C, 40
fraction apoB, TG
Hypercholesterolemic (>5.69) 20/21 Randomised, double-blind Tocotrienols 200 mg 12 weeks ↓TC, LDL-C, 41
apoB
Hypercholesterolemic 15/- Cross-over Rice bran oil 50 g 5 weeks ↓TC, LDL-C 42
(0.71 ± 0.06)
Climacteric disturbance (≥0.57) 40/- — γ-Oryzanol 300 mg 8 weeks ↓TC, TG, 43
↑HDL-C

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Review
has been shown to reduce the blood glucose level and serum
lipid parameters in humans significantly.54 Thus, RBF is
suggested for use in weight loss programs and therapeutic
fiber diets for patients with type 1 and 2 diabetes mellitus.
A high soluble dietary fiber intake is emphasized in the diet
recommendations of most patients with obesity and diabetes
because the viscous and gel-forming properties of dietary fiber
inhibit macronutrient absorption, reduce postprandial glucose
response, and positively influence certain blood lipids.55,56 In
addition, fructo-oligosaccharides in rice bran play a role as pre-
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biotics by promoting gut microbiota to proliferate in the gastro-
intestinal track and improving intestinal and colon health.57
2.4. Other health beneficial components
The other beneficial constituent of rice bran includes pheno-
lics consisting of phenoic acids and flavonoids that have been
investigated as antioxidants and antimicrobials.58 In total,
there are more than 100 antioxidants identified in rice bran
and its products.37 Most of the antioxidants are grouped into
phenolic acids and flavonoids. There are twelve phenolic acids
having antioxidative activities in rice bran, ranging from 177.6
to 319.8 mg per 100 g depending on the rice color.59 These are
ferulic acid (120.3 mg per 100 g), followed by p-coumaric acid
(42.2 mg per 100 g), p-hydroxybenzoic acid (3.7 mg per 100 g),
sinapic acid (2.1 mg per 100 g), and gallic acid (1.4 mg per
100 g).60 Those with minor constituents (less than 1.0 mg per
100 g) include protocatechuic, vanillic, caffeic, and syringic
acids.61 Other antioxidative components in rice bran are
the diverse flavonoids present in both pigmented and non-
pigmented rice bran at a concentration of 1402.3 and 576.8 mg
catechin equivalent per 100 g, respectively.62 These flavonoids
are present in the following decreasing order in concentration:
tricin, luteolin, apigenin, quercetin, isorhamnetin, kaempferol,
and myricetin.60 The phytochemicals and micronutrients in
rice bran need to be further investigated for their functional
properties and compositional diversities.
3. Rice bran as an immunomodulator
Currently, there are many clinical trials demonstrating an
improvement in depressed immune functions by using dietary
food ingredients that aim to reduce infection rates and
mitigate infectious diseases.63,64 Therefore, foods capable of
enhancing the immune response of patients with disturbed
immune functions are valuable. Moreover, the proliferation,
survival, migration, and tumor growth of cancer cells are
accelerated when the immune function is disturbed.65 It has
also been shown that individuals with lowered immune-
mediated cell activities are subject to higher rates of cancer
incidence and metastasis.66
The immune system is a remarkably adaptive defense system
against invading pathogens therefore preventing diseases from
occurring. Vertebrates use defense strategies that depend on
innate immune responses as a first line of defense, but they can
also mount much more sophisticated defenses, called adaptive
immune responses.67 The innate responses involve the adaptive
immune responses on the boundary for eliminating the causes
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of disease in the host on a time lag. The early innate systems
of defense, which are not specific to a particular pathogen,
become quickly activated to help destroy invaders and are
equally important to activate the adaptive immunity.68 However,
adaptive responses are highly specific to a particular pathogen
and can also provide long-lasting protection.
In addition, the role and need for immune responses are
prominent during chemotherapeutic intervention used for the
treatment of many diseases. Modulation of the immune
response to regulate disease-causing pathogens has been of
interest for many years. Furthermore, in earlier reports it has
been demonstrated that the oral administration of rice bran
extracts represented a promising dietary intervention to modu-
late cellular and humoral immunity for protection against
infections.69 However, active immunomodulators isolated and
characterized from rice bran usually are large molecules and
have not been investigated in detail.
3.1. Rice bran components as immunomodulators
Numerous studies reported that potent antioxidants in rice
bran included immune system enhancing compounds, such as
phytosterols, polysaccharides, minerals and trace minerals
including magnesium, selenium, zinc, vitamin E, omega-3
fatty acids and several other phytonutrients.37 The primary
effect of botanical polysaccharides is to enhance and/or acti-
vate innate immunity and macrophage and natural killer (NK)
cell immune responses, leading to immunomodulation, anti-
tumor activity, wound-healing and other therapeutic effects.70
There are several reports on the immunomodulation of
phytosterols on liver carcinogenesis,71 infection,72 and gastro-
intestinal injury,73 via the role of immunoregulatory transcrip-
tion factors and their dependent antiapoptotic gene products.74,75
The opposite side of the immune-enhancing effects is that rice
bran components as COX-2 inhibitors are potent mediators
of inflammation, which help suppress the hypersensitive
response also known as allergy.76
3.2. Polysaccharide as an immunomodulator
Previous studies have reported that plant-extracted poly-
saccharides activated the immune response of the host
organism.49 The immunomodulatory properties of the poly-
saccharides depend on them binding on the surface receptor
of immune cells. These receptors are known as pattern
recognition molecules and recognize foreign ligands during
the early stage of the immune response.
Several dietary fibers contained in rice bran, such as
arabinoxylan and β-glucan, have been suggested to be functional
polysaccharides with immunomodulatory properties.77 The
potential biological activities of rice bran polysaccharides have
drawn increasing attention from natural product researchers
as they have been found to exhibit anticancer properties,
which inhibit the growth of various types of tumors such as
gastrointestinal cancers,78 mammary tumors,79 and Lewis lung
carcinomas.80 These antitumor activities mainly related to the
immunomodulation and activation of the tumor-suppressed
host immune system. The other anti-tumor effect of rice bran
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Food & Function
polysaccharides is thought to be a cytotoxic effect inducing
cell apoptosis or cell-cycle arrest mediated by NK cells,
macrophages, and T-lymphocytes.81 To date, however, the
mechanism by which rice bran polysaccharides increase the
anti-tumor activity remains unknown.
Arabinoxylan (MGN-3) from rice bran exerts prominent
immune-mediated anti-cancer activity against neuroblastoma,
breast cancer, and leukemia in vivo.82 The antitumor activity of
MGN-3 depends on the activation of immune mediated cells
such as NK cells, T and B cells, and macrophages and the
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released level of immune-mediated cytokines such as IFN-γ,
TNF-α, and ILs. These findings may support the anti-tumor
activity of rice bran polysaccharides, which was previously
thought to be exerted mainly through the activation of the
host immune system.
The modification of the structure is usually considered the
most effective way to enhance the immunomodulatory activi-
ties of polysaccharides. Sulfated polysaccharides exert excellent
bioactivities during antitumor effects,83 and possess immuno-
modulatory activities84 that may be of potential application in
modulating the immune response in order to mitigate the
associated negative effects such as inflammation.85 Sulfated
polysaccharides may affect multiple targets in the immune
system that in turn can have an impact on disease improve-
ment including tumor progression and metastasis.86
Moreover, polysaccharide-binding protein complexes and
glycoproteins also exist in the protein extract of rice bran,87
and have distinct immunomodulatory roles in immuno-
suppression,23 antitumor properties,88 and irritable bowel syn-
drome.53 The glycan structure not only influences the function
of immune molecules, but also influences the immune
response.89 However, the glycan function is highly specific to a
particular glycoprotein and it often depends on glycan-binding
proteins, such as galectins, sialic acid binding Ig-like lectins,
and C-type lectin receptors.90
3.3. Proteins and peptides as immunomodulators
Numerous studies have reported that naturally isolated bio-
active proteins and peptides could exert an immunomodula-
tory effect.91 These proteins and peptides can regulate the pro-
duction of certain cytokines, stimulate the phagocytic activities
of macrophages, and modulate the proliferation of immune-
mediated cells such as lymphocytes.92,93
Bioactive peptides that modulate and stimulate the
immune system can enhance immune cell functions,
measured as lymphocyte proliferation, NK cell activity, anti-
body synthesis, and cytokine regulation and can reduce
allergic reactions and enhance mucosal immunity in the
gastrointestinal tract.94 Oryzatensin is a bioactive peptide that
is isolated from the tryptic digest of rice albumin and has a
sequence of amino acids Gly-Tyr-Pro-Met-Tyr-Pro-Leu-Pro-Arg
which was shown to have an immunostimulatory role that is
mediated by histamine release.51 Although rice bran has a
diverse source of protein and glycan moieties, there have only
been a few studies on immune modulation. More studies on
the immunomodulatory effect of rice bran protein are needed.
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3.4. Oils as immunomodulators
The administration of rice bran oryzanol with dosages at
50 and 100 mg kg−1 ameliorated myelosuppression in cyclo-
phosphamide-treated rats and showed an increase in the
phagocytic index of the carbon clearance assay.95 Destruction
of T and immune-related cells is the major drawback of cyclo-
phosphamide therapy. Oryzanol treatment provides sufficient
evidence to overcome the side effects of cyclophosphamide-
induced myelosuppression.
3.5. Micronutrients as immunomodulators
There is strong evidence in animal and clinical studies that
nutrition plays a role in modulating the immune function and
that the immune system needs a reasonable supply of nutri-
ents to maintain intact function. The list of micronutrients
contained in rice bran, which have a significant influence on
the immune function in vivo includes several vitamins, zinc,
copper, iron, and selenium magnesium.
Several vitamins such as vitamin E, B6, and K present in
rice bran also modulate the immune system. Representatively,
vitamin E, a lipid-soluble antioxidant, is considered the first
line of defense against lipid peroxidation and its deficiency
influences both T- and B-cell function.96 Vitamin B6 and K
supplementation also has a beneficial effect on immune
responses.97
Tocotrienols have been shown to possess immunomodu-
latory effects in murine lymphocytes.75 Among the four
different forms of tocotrienol, γ-tocotrienol was more
effective in suppressing concanavalin A-induced T cell pro-
liferation and cytokine production compared to α-tocotrienol
when present continuously in the culture. The antitumor
effects of γ-tocotrienol have recently been shown to be
mediated via the inhibition of the nuclear factor kappa-light-
chain-enhancer of activated B cells (NF-κB) which is a
transcription factor that participates in the induction of
numerous immunoregulatory genes.74 The activation of NF-
κB plays an essential role in T cell activation in response to a
variety of stimuli.
Zinc is a cofactor for more than 300 enzymes, and is
involved in innate immune function, mucosal immune system
function, lymphopoiesis, and T-cell regulation. Zinc can down-
regulate most of the immune functions and its deficiency
causes diseases like lethal trait A46 and death due to
impairment of the immune system.98 Several studies have also
demonstrated that copper regulates macrophages’ anti-
microbial functions and that macrophages from copper
deficient rats were unimpaired in their ability to phagocytose
erythrocytes.99 Minerals are essential nutrients in human
beings and include iron, selenium, and magnesium, all of
which participate in the immune function.
4. Conclusion remarks
In this study, we reviewed the potential of rice bran to serve as
an immunomodulator and as a functional ingredient for the
Food Funct.

Review
immune system. The functional constituents of rice bran such
as polysaccharides, proteins, and oils, which contribute to
immune responses, need to be investigated. The role of rice
bran in the modulation of the immune system needs further
study to characterize the moieties.
Although most of the rice bran products are waste products
in the agricultural industry, recent scientific reports have
recognized rice bran’s potential health benefits. The merit of
rice bran is that it has more than 100 antioxidants and is com-
posed of balanced nutrients such as oils, fibers, proteins, and
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other micronutrients. Rice bran and its constituents and
phytonutrients are widely used by the feed and food industry
as supplements, although their nutritional and functional
properties make them also suitable for other purposes, such
as functional foods. The widely demonstrated beneficial
effects of rice bran on several diseases, including cancers,
hyperlipidemia, and cardiovascular disease, appear to be
related to the functional properties of the many vitamins and
minerals as well as oils, polysaccharides, and proteins which
operate through a specific immune response. Thus, more
mechanistic studies and randomized controlled clinical trials
are necessary to confirm these effects.
Rice bran and its derivatives have been noted for their
potential health benefits through immunomodulation.
However, the potential benefits of several components reside
in active ingredients. For example, active ingredients include
water-soluble extracts for polysaccharides, crude protein
extracts for RBP and GRB, and solvent extraction for RBOs.
These phytonutrients and antioxidants of rice bran act on
physiological states. In addition, the synergistic function
between rice bran components is responsible for the positive
health benefits. We hope that future studies will also confirm
rice bran as suitable for use in the routine management of
health conditions because of its properties in enhancing the
immune status.
References
1 T. T. Chang, in Rice: origin, History, Technology and
Production, ed. C. W. Smith and R. H. Dilday, John Wiley
and Sons. Inc., NJ, USA, 2003, pp. 3–25.
2 FAO, FAO rice market monitor, Food and Agriculture
Organization (FAO), Rome, Italy, 2015.
3 P. Roy, T. Orikasa, H. Okadome, N. Nakamura and
T. Shiina, Processing conditions, rice properties, health
and environment, Int. J. Environ. Res. Public. Health, 2011,
8, 1957–1976.
4 M. W. Trucksess, H. K. Abbas, C. M. Weaver and
W. T. Shier, Distribution of aflatoxins in shelling and
milling fractions of naturally contaminated rice, Food
Addit. Contam., Part A, 2011, 28, 1076–1082.
5 E. T. Champagne, D. F. Wood, B. O. Juliano and
D. B. Bechtel, in Rice: Chemistry and Technology, ed.
E. T. Champagne, American Association of Cereal
Chemists, Inc., St. Paul, MN, 3rd edn, 2004, pp. 77–107.
Food Funct.
View Article Online
Food & Function
6 M. K. Sharif, M. S. Butt, F. M. Anjum and S. H. Khan, Rice
bran: a novel functional ingredient, Crit. Rev. Food Sci.
Nutr., 2014, 54, 807–816.
7 R. J. Jariwalla, Rice-bran products: phytonutrients with
potential applications in preventive and clinical medicine,
Drugs Exp. Clin. Res., 2001, 27, 17–26.
8 N. Samad, Rice bran oil prevents neuroleptic-induced extra-
pyramidal symptoms in rats: Possible antioxidant mecha-
nisms, J. Food Drug Anal., 2015, 23, 370–375.
9 F. S. Taha, R. M. Mourad, S. S. Mohamed and
A. I. Hashem, Enzymatic pretreatment of stabilized rice
bran with mixed enzymes: evaluation of oil, Am. J. Food
Technol., 2012, 7, 452–469.
10 R. M. Saunders, Rice bran: Composition and potential food
uses, Food Rev. Int., 1985, 1, 465–495.
11 B. O. Juliano, in Rice: Chemistry and Technology, American
Association of Cereal Chemists, St. Paul, MN, 1985.
12 M. Wang, N. S. Hettiarachchy, M. Qi, W. Burks and
T. Siebenmorgen, Preparation and functional properties of
rice bran protein isolate, J. Agric. Food Chem., 1999, 47,
411–416.
13 I. Sereewatthanawut, S. Prapintip, K. Watchiraruji, M. Goto,
M. Sasaki and A. Shotipruk, Extraction of protein and
amino acids from deoiled rice bran by subcritical water
hydrolysis, Bioresour. Technol., 2008, 99, 555–561.
14 S. W. Han, K. M. Chee and S. J. Cho, Nutritional quality of
rice bran protein in comparison to animal and vegetable
protein, Food Chem., 2015, 172, 766–769.
15 T. Chittapalo and A. Noomhorm, Ultrasonic assisted alkali
extraction of protein from defatted rice bran and properties
of the protein concentrates, Int. J. Food Sci. Technol., 2009,
44, 1843–1849.
16 S. Tang, N. S. Hettiarachchy and T. H. Shellhammer,
Protein extraction from heat-stabilized defatted rice
bran. 1. Physical processing and enzyme treatments,
J. Agric. Food Chem., 2002, 50, 7444–7448.
17 C. Fabian and Y. H. Ju, A review on rice bran protein: its
properties and extraction methods, Crit. Rev. Food Sci.
Nutr., 2011, 51, 816–827.
18 K. A. Meldenhauer, E. T. Champagne, D. R. McCaskill and
H. Guraya, in Functional foods: biochemical and processing
aspects, ed. G. Mazza, Technomic Publishing Company,
Inc., Lancaster, PA, 1998, pp. 71–89.
19 S. Agboola, D. Ng and D. Mills, Characterisation and func-
tional properties of Australian rice protein isolates,
J. Cereal Sci., 2005, 41, 283–290.
20 R. Gnanasambandam and N. S. HelTiarachchy, Protein
concentrates from unstabilized and stabilized rice bran:
preparation and properties, J. Food Sci., 1995, 60, 1066–
1069.
21 L. Wattanasiritham, C. Theerakulkait, S. Wickramasekara,
C. S. Maier and J. F. Stevens, Isolation and identification of
antioxidant peptides from enzymatically hydrolyzed rice
bran protein, Food Chem., 2016, 192, 156–162.
22 A. P. Adebiyi, A. O. Adebiyi, T. Ogawa and K. Muramoto,
Purification and characterisation of antioxidative peptides
This journal is © The Royal Society of Chemistry 2017

Food & Function
from unfractionated rice bran protein hydrolysates,
Int. J. Food Sci. Technol., 2008, 43, 35–43.
23 H. Y. Park, A. R. Yu, H. D. Hong, H. H. Kim, K. W. Lee and
H. D. Choi, Immunomodulatory effects of nontoxic glyco-
protein fraction isolated from rice bran, Planta Med., 2016,
82, 606–611.
24 O. Boonla, U. Kukongviriyapan, P. Pakdeechote,
V. Kukongviriyapan, P. Pannangpetch and
S. Thawornchinsombut, Peptides-derived from Thai rice
bran improves endothelial function in 2K-1C renovascular
Published on 10 February 2017. Downloaded by Fudan University on 23/02/2017 19:45:46.
hypertensive rats, Nutrients, 2015, 7, 5783–5799.
25 A. Kannan, N. Hettiarachchy and S. Narayan, Colon and
breast anti-cancer effects of peptide hydrolysates derived
from rice bran, Open Bioact. Compd. J., 2009, 2, 17–20.
26 G. H. Li, M. R. Qu, J. Z. Wan and J. M. You,
Antihypertensive effect of rice protein hydrolysate with
in vitro angiotensin I-converting enzyme inhibitory activity
in spontaneously hypertensive rats, Asia Pac. J. Clin. Nutr.,
2007, 16(Suppl 1), 275–280.
27 K. Boonloh, U. Kukongviriyapan, P. Pannangpetch,
B. Kongyingyoes, L. Senggunprai, A. Prawan,
S. Thawornchinsombut and V. Kukongviriyapan, Rice bran
protein hydrolysates prevented interleukin-6- and high
glucose-induced insulin resistance in HepG2 cells, Food
Funct., 2015, 6, 566–573.
28 N. Cheetangdee, Effects of rice bran protein hydrolysates
on the physicochemical stability of oil-in-water emulsions,
J. Oleo Sci., 2014, 63, 1231–1241.
29 A. Rafe, S. S. Mousavi and S.-A. Shahidi, Dynamic rheologi-
cal behavior of rice bran protein (RBP): Effects of concen-
tration and temperature, J. Cereal Sci., 2014, 60, 514–519.
30 S. Kubglomsong and C. Theerakulkait, Effect of rice bran
protein extract on enzymatic browning inhibition in vege-
table and fruit puree, Kasetsart J., 2014, 48, 205–213.
31 M. Majzoobi, S. Sharifi, B. Imani and A. Farahnaky, The
effect of particle size and level of rice bran on the batter
and sponge cake properties, J. Agric. Sci. Technol., 2013, 15,
1175–1184.
32 F. Odabasoglu, Z. Halici, A. Cakir, M. Halici, H. Aygun,
H. Suleyman, E. Cadirci and F. Atalay, Beneficial effects of
vegetable oils (corn, olive and sunflower oils) and
α-tocopherol on anti-inflammatory and gastrointestinal
profiles of indomethacin in rats, Eur. J. Pharmacol., 2008,
591, 300–306.
33 M. M. Most, R. Tulley, S. Morales and M. Lefevre, Rice bran
oil, not fiber, lowers cholesterol in humans, Am. J. Clin.
Nutr., 2005, 81, 64–68.
34 S. Eady, A. Wallace, J. Willis, R. Scott and C. Frampton,
Consumption of a plant sterol-based spread derived from
rice bran oil is effective at reducing plasma lipid levels in
mildly hypercholesterolaemic individuals, Br. J. Nutr., 2011,
105, 1808–1818.
35 Y. Liang, Y. Gao, Q. Lin, F. Luo, W. Wu, Q. Lu and Y. Liu,
A review of the research progress on the bioactive
ingredients and physiological activities of rice bran oil, Eur.
Food Res. Technol., 2014, 238, 169–176.
This journal is © The Royal Society of Chemistry 2017
View Article Online
Review
36 K. J. Reddy, K. Jayathilakan and M. C. Pandey, Effect of
ionizing radiation on the protein and lipid quality charac-
teristics of mutton kheema treated with rice bran oil and
sunflower oil, Radiat. Phys. Chem., 2015, 117, 217–224.
37 R. Cheruvanky, in Phytochemical functional foods, ed.
I. T. Johnson and G. Williamson, Woodhead Publishing
Limited, Cambridge, England, 2003, pp. 347–376.
38 A. G. G. Krishna, K. H. Hemakumar and S. Khatoon, Study
on the composition of rice bran oil and its higher free fatty
acids value, J. Am. Oil Chem. Soc., 2006, 83, 117–120.
39 A. L. Gerhardt and N. B. Gallo, Full-fat rice bran and oat
bran similarly reduce hypercholesterolemia in humans,
J. Nutr., 1998, 128, 865–869.
40 A. A. Qureshi, S. A. Sami, W. A. Salser and F. A. Khan, Dose-
dependent suppression of serum cholesterol by tocotrie-
nol-rich fraction (TRF25) of rice bran in hypercholesterole-
mic humans, Atherosclerosis, 2002, 161, 199–207.
41 A. A. Qureshi, B. A. Bradlow, W. A. Salser and L. D. Brace,
Novel tocotrienols of rice bran modulate cardiovascular
disease risk parameters of hypercholesterolemic humans,
J. Nutr. Biochem., 1997, 8, 290–298.
42 A. H. Lichtenstein, L. M. Ausman, W. Carrasco,
L. J. Gualtieri, J. L. Jenner, J. M. Ordovas, R. J. Nicolosi,
B. R. Goldin and E. J. Schaefer, Rice bran oil consumption
and plasma lipid levels in moderately hypercholesterolemic
humans, Arterioscler. Thromb., 1994, 14, 549–556.
43 M. Ishihara, Y. Ito, T. Nakakita, T. Maehama, S. Hieda,
K. Yamamoto and N. Ueno, Clinical effect of gamma-oryza-
nol on climacteric disturbance -on serum lipid peroxides,
Nihon Sanka Fujinka Gakkai Zasshi, 1982, 34, 243–251.
44 C.-K. Shih, C.-J. Ho, S.-C. Li, S.-H. Yang, W.-C. Hou and
H.-H. Cheng, Preventive effects of rice bran oil on 1,2-di-
methylhydrazine/dextran sodium sulphate-induced colon
carcinogenesis in rats, Food Chem., 2011, 126, 562–567.
45 S. Siddiqui, H. Ahsan, M. R. Khan and W. A. Siddiqui,
Protective effects of tocotrienols against lipid-induced
nephropathy in experimental type-2 diabetic rats by modu-
lation in TGF-beta expression, Toxicol. Appl. Pharmacol.,
2013, 273, 314–324.
46 T. Yamagishi, T. Tsuboi and K. Kikuchi, Potent natural
immunomodulator, rice water-soluble polysaccharide frac-
tions with anticomplementary activity, Cereal Chem., 2003,
80, 5–8.
47 L. Shi, Bioactivities, isolation and purification methods of
polysaccharides from natural products: A review, Int. J. Biol.
Macromol., 2016, 92, 37–48.
48 S. K. Singdevsachan, P. Auroshree, J. Mishra,
B. Baliyarsingh, K. Tayung and H. Thatoi, Mushroom poly-
saccharides as potential prebiotics with their antitumor
and immunomodulating properties: A review, Bioact.
Carbohydr. Diet. Fibre, 2016, 7, 1–14.
49 A. O. Tzianabos, Polysaccharide immunomodulators as
therapeutic agents: structural aspects and biologic func-
tion, Clin. Microbiol. Rev., 2000, 13, 523–533.
50 S. A. S. C. Faria, P. Z. Bassinello and M. V. C. Penteado,
Nutritional composition of rice bran submitted to different
Food Funct.

Review
stabilization procedures, Braz. J. Pharm. Sci., 2012, 48, 651–
657.
51 A. Abdul-Hamid and Y. S. Luan, Functional properties of
dietary fibre prepared from defatted rice bran, Food Chem.,
2000, 68, 15–19.
52 M. Salehifar and V. Fadaei, Comparison of some functional
properties and chemical constituents of dietary fibers of
Iranian rice bran extracted by chemical and enzymatic
methods, Afr. J. Biotechnol., 2011, 10, 18528–18531.
53 T. Kamiya, M. Shikano, M. Tanaka, K. Ozeki, M. Ebi,
Published on 10 February 2017. Downloaded by Fudan University on 23/02/2017 19:45:46.
T. Katano, S. Hamano, H. Nishiwaki, H. Tsukamoto,
T. Mizoshita, Y. Mori, E. Kubota, S. Tanida, H. Kataoka,
N. Okuda and T. Joh, Therapeutic effects of biobran, modi-
fied arabinoxylan rice bran, in improving symptoms of
diarrhea predominant or mixed type irritable bowel syn-
drome: a pilot, randomized controlled study, J. Evidence-
Based Complementary Altern. Med., 2014, 2014, 6.
54 A. A. Qureshi, S. A. Sami and F. A. Khan, Effects of stabil-
ized rice bran, its soluble and fiber fractions on blood
glucose levels and serum lipid parameters in humans with
diabetes mellitus Types I and II, J. Nutr. Biochem., 2002, 13,
175–187.
55 M. O. Weickert and A. F. Pfeiffer, Metabolic effects of
dietary fiber consumption and prevention of diabetes,
J. Nutr., 2008, 138, 439–442.
56 J. Qi, Y. Li, W. Yokoyama, H. Majeed, K. G. Masamba,
F. Zhong and J. Ma, Cellulosic fraction of rice bran fibre
alters the conformation and inhibits the activity of porcine
pancreatic lipase, J. Funct. Foods, 2015, 19(Part A), 39–48.
57 A. L. Dominguez, L. R. Rodrigues, N. M. Lima and
J. A. Teixeira, An overview of the recent developments on
fructooligosaccharide production and applications, Food
Bioprocess Technol., 2013, 7, 324–337.
58 M. d. S. Oliveira, E. P. Cipolatti, E. B. Furlong and
L. d. S. Soares, Phenolic compounds and antioxidant
activity in fermented rice (Oryza sativa) bran, Food Sci.
Technol., 2012, 32, 531–537.
59 A. Mahender, A. Anandan, S. K. Pradhan and E. Pandit,
Rice grain nutritional traits and their enhancement using
relevant genes and QTLs through advanced approaches,
Springerplus, 2016, 5, 2086.
60 P. Goufo and H. Trindade, Rice antioxidants: phenolic
acids, flavonoids, anthocyanins, proanthocyanidins, toco-
pherols, tocotrienols, gamma-oryzanol, and phytic acid,
Food Sci. Nutr., 2014, 2, 75–104.
61 S.-M. Kim and S.-T. Lim, Enhanced antioxidant activity of
rice bran extract by carbohydrase treatment, J. Cereal Sci.,
2016, 68, 116–121.
62 P. Goufo, J. Pereira, N. Figueiredo, M. B. P. P. Oliveira,
C. Carranca, E. A. S. Rosa and H. Trindade, Effect of elevated
carbon dioxide (CO2) on phenolic acids, flavonoids, toco-
pherols, tocotrienols, γ-oryzanol and antioxidant capacities
of rice (Oryza sativa L.), J. Cereal Sci., 2014, 59, 15–24.
63 M. O’Shea, J. Bassaganya-Riera and I. C. Mohede,
Immunomodulatory properties of conjugated linoleic acid,
Am. J. Clin. Nutr., 2004, 79, 1199S–1206S.
Food Funct.
View Article Online
Food & Function
64 H. M. Delagreverie, C. Delaugerre, S. R. Lewin, S. G. Deeks
and J. Z. Li, Ongoing clinical trials of human immuno-
deficiency virus latency-reversing and immunomodulatory
agents, Open Forum Infect. Dis., 2016, 3, ofw189.
65 S. Kaminogawa and M. Nanno, Modulation of immune
functions by foods, J. Evidence-Based Complementary Altern.
Med., 2004, 1, 241–250.
66 R. Subramaniam, A. Mizoguchi and E. Mizoguchi,
Mechanistic roles of epithelial and immune cell signaling
during the development of colitis-associated cancer, Cancer
Res. Front., 2016, 2, 1–21.
67 B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts and
P. Walter, The adaptive immune system, Garland Science,
New York, NY, 2002.
68 C. A. Janeway, P. Travers, M. Walport and M. J. Shlomchik,
Immunobiology, Garland Science, New York, NY, 5th edn,
2001.
69 A. J. Henderson, A. Kumar, B. Barnett, S. W. Dow and
E. P. Ryan, Consumption of rice bran increases mucosal
immunoglobulin A concentrations and numbers of intesti-
nal Lactobacillus spp., J. Med. Food, 2012, 15, 469–475.
70 I. A. Schepetkin and M. T. Quinn, Botanical polysacchar-
ides: macrophage immunomodulation and therapeutic
potential, Int. Immunopharmacol., 2006, 6, 317–333.
71 S. Wada, Y. Satomi, M. Murakoshi, N. Noguchi,
T. Yoshikawa and H. Nishino, Tumor suppressive effects of
tocotrienol in vivo and in vitro, Cancer Lett., 2005, 229,
181–191.
72 T. B. Elliott, D. L. Bolduc, G. D. Ledney, J. G. Kiang,
O. O. Fatanmi, S. Y. Wise, P. L. Romaine, V. L. Newman
and V. K. Singh, Combined immunomodulator and anti-
microbial therapy eliminates polymicrobial sepsis and
modulates cytokine production in combined injured mice,
Int. J. Radiat. Biol., 2015, 91, 690–702.
73 X. H. Li, S. P. Ghosh, C. T. Ha, D. Fu, T. B. Elliott,
D. L. Bolduc, V. Villa, M. H. Whitnall, M. R. Landauer and
M. Xiao, Delta-tocotrienol protects mice from radiation-
induced gastrointestinal injury, Radiat. Res., 2013, 180,
649–657.
74 K. S. Ahn, G. Sethi, K. Krishnan and B. B. Aggarwal,
Gamma-tocotrienol inhibits nuclear factor-kappaB signal-
ing pathway through inhibition of receptor-interacting
protein and TAK1 leading to suppression of antiapoptotic
gene products and potentiation of apoptosis, J. Biol. Chem.,
2007, 282, 809–820.
75 C. Wilankar, D. Sharma, R. Checker, N. M. Khan,
R. Patwardhan, A. Patil, S. K. Sandur and T. P. A. Devasagayam,
Role of immunoregulatory transcription factors in differ-
ential immunomodulatory effects of tocotrienols, Free
Radicals Biol. Med., 2011, 51, 129–143.
76 S. P. Choi, S. P. Kim, M. Y. Kang, S. H. Nam and
M. Friedman, Protective effects of black rice bran against
chemically-induced inflammation of mouse skin, J. Agric.
Food Chem., 2010, 58, 10007–10015.
77 H. Maeda, K. Ichihashi, T. Fujii, K. Omura, X. Zhu,
M. Anazawa and K. Tazawa, Oral administration of hydro-
This journal is © The Royal Society of Chemistry 2017

Food & Function
lyzed rice bran prevents the common cold syndrome in the
elderly based on its immunomodulatory action, Biofactors,
2004, 21, 185–187.
78 M. Takeshita, S. Nakamura, F. Makita, S. Ohwada,
Y. Miyamoto and Y. Morishita, Antitumor effect of RBS
(rice bran saccharide) on ENNG-induced carcinogenesis,
Biotherapy, 1992, 4, 139–145.
79 L. Wang, H. Huang, Y. Wei, X. Li and Z. Chen,
Characterization and anti-tumor activities of sulfated poly-
saccharide SRBPS2a obtained from defatted rice bran,
Published on 10 February 2017. Downloaded by Fudan University on 23/02/2017 19:45:46.
Int. J. Biol. Macromol., 2009, 45, 427–431.
80 S. Takeo, H. Kado, H. Yamamoto, M. Kamimura,
N. Watanabe, K. Uchida and Y. Mori, Studies on an anti-
tumor polysaccharide RBS derived from rice bran. II.
Preparation and general properties of RON, an active frac-
tion of RBS, Chem. Pharm. Bull., 1988, 36, 3609–3613.
81 K. Takeda, K. Tomimori, R. Kimura, C. Ishikawa,
T. K. Nowling and N. Mori, Anti-tumor activity of fucoidan
is mediated by nitric oxide released from macrophages,
Int. J. Oncol., 2012, 40, 251–260.
82 A. Pérez-Martínez, J. Valentín, L. Fernández, E. Hernández-
Jiménez, E. López-Collazo, P. Zerbes, E. Schwörer,
F. Nuñéz, I. G. Martín, H. Sallis, M. Á. Díaz,
R. Handgretinger and M. M. Pfeiffer, Arabinoxylan rice
bran (MGN-3/Biobran) enhances natural killer cell–
mediated cytotoxicity against neuroblastoma in vitro and
in vivo, Cytotherapy, 2015, 17, 601–612.
83 L. Wang, Y. Li, L. Zhu, R. Yin, R. Wang, X. Luo, Y. Li, Y. Li
and Z. Chen, Antitumor activities and immunomodulatory
of rice bran polysaccharides and its sulfates in vitro,
Int. J. Biol. Macromol., 2016, 88, 424–432.
84 G. Jiao, G. Yu, J. Zhang and H. S. Ewart, Chemical struc-
tures and bioactivities of sulfated polysaccharides from
marine algae, Mar. Drugs, 2011, 9, 196–223.
85 D. Chen, X. Z. Wu and Z. Y. Wen, Sulfated polysaccharides
and immune response: promoter or inhibitor?, Panminerva
Med., 2008, 50, 177–183.
86 I. Groth, N. Grunewald and S. Alban, Pharmacological pro-
files of animal- and nonanimal-derived sulfated polysac-
charides–comparison of unfractionated heparin, the
semisynthetic glucan sulfate PS3, and the sulfated poly-
saccharide fraction isolated from Delesseria sanguinea,
Glycobiology, 2009, 19, 408–417.
This journal is © The Royal Society of Chemistry 2017
View Article Online
Review
87 H. Y. Park, A. R. Yu, I. W. Choi, H. D. Hong, K. W. Lee and
H. D. Choi, Immunostimulatory effects and characteriz-
ation of a glycoprotein fraction from rice bran, Int.
Immunopharmacol., 2013, 17, 191–197.
88 H. Y. Kim, J. H. Kim, S. B. Yang, S. G. Hong, S. A. Lee,
S. J. Hwang, K. S. Shin, H. J. Suh and M. H. Park, A poly-
saccharide extracted from rice bran fermented with
Lentinus edodes enhances natural killer cell activity and
exhibits anticancer effects, J. Med. Food, 2007, 10, 25–31.
89 X. L. Zhang, Roles of glycans and glycopeptides in immune
system and immune-related diseases, Curr. Med. Chem.,
2006, 13, 1141–1147.
90 J. L. Johnson, M. B. Jones, S. O. Ryan and B. A. Cobb, The
regulatory power of glycans and their binding partners in
immunity, Trends Immunol., 2013, 34, 290–298.
91 E. F. Haney and R. E. Hancock, Peptide design for anti-
microbial and immunomodulatory applications,
Biopolymers, 2013, 100, 572–583.
92 H. Korhonen and A. Pihlanto, Bioactive peptides:
Production and functionality, Int. Dairy J., 2006, 16, 945–
960.
93 H. Meisel, Multifunctional peptides encrypted in milk pro-
teins, Biofactors, 2004, 21, 55–61.
94 R. Hartmann and H. Meisel, Food-derived peptides with
biological activity: from research to food applications, Curr.
Opin. Biotechnol., 2007, 18, 163–169.
95 S. B. Ghatak and S. J. Panchal, Investigation of the
immunomodulatory potential of oryzanol isolated from
crude rice bran oil in experimental animal models,
Phytother. Res., 2012, 26, 1701–1708.
96 D. Pekmezci, Vitamin E and immunity, Vitam. Horm., 2011,
86, 179–215.
97 C. H. Cheng, S. J. Chang, B. J. Lee, K. L. Lin and
Y. C. Huang, Vitamin B6 supplementation increases
immune responses in critically ill patients, Eur. J. Clin.
Nutr., 2006, 60, 1207–1213.
98 L. E. Perryman, D. R. Leach, W. C. Davis, W. D. Mickelsen,
S. R. Heller, H. D. Ochs, J. A. Ellis and E. Brummerstedt,
Lymphocyte alterations in zinc-deficient calves with lethal
trait A46, Vet. Immunol. Immunopathol., 1989, 21, 239–248.
99 U. Babu and M. L. Failla, Respiratory burst and candidaci-
dal activity of peritoneal macrophages are impaired in
copper-deficient rats, J. Nutr., 1990, 120, 1692–1699.
Food Funct.