1-s2.0-S0899900713002207-main

Nutrition 30 (2014) 134–144
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Nutrition
journal homepage: www.nutritionjrnl.com
Review
Edible berries: Bioactive components and their effect
on human health
Shivraj Hariram Nile M.Sc., Ph.D. *, Se Won Park M.Sc., Ph.D. *
Department of Molecular Biotechnology, College of Life and Environmental Sciences, Konkuk University, Seoul, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 March 2013
Accepted 11 April 2013
The importance of food consumption in relation to human health has increased consumer attention in nutraceutical components and foods, especially fruits and vegetables. Berries are a rich
source of a wide variety of non-nutritive, nutritive, and bioactive compounds such as flavonoids,
phenolics, anthocyanins, phenolic acids, stilbenes, and tannins, as well as nutritive compounds
such as sugars, essential oils, carotenoids, vitamins, and minerals. Bioactive compounds from
berries have potent antioxidant, anticancer, antimutagenic, antimicrobial, anti-inflammatory, and
antineurodegenerative properties, both in vitro and in vivo. The following is a comprehensive and
critical review on nutritional and non-nutritional bioactive compounds of berries including their
absorption, metabolism, and biological activity in relation to their potential effect on human
health.
Ó 2014 Elsevier Inc. All rights reserved.
Keywords:
Phytochemicals
Human health
Blueberries
Blackberries
Raspberries
Strawberries
Introduction
Increased consumption of fruits and vegetables is recommended in dietary guidelines worldwide and the intake of fruits
like berries which are rich in nutrients and phytochemicals
can prevent various diseases and disorders. Most berries are
delicious and powerful disease-fighting foods and make up the
largest proportion of fruit that is consumed in the human diet
[1]. Berry fruits are popularly consumed not only in fresh and
frozen forms but also as processed and derived products,
including dried and canned fruits, yogurts, beverages, jams, and
jellies [2]. Among the colorful fruits, berries such as blackberry
(Rubus species), black raspberry (Rubus occidentalis), blueberry
(Vaccinium corymbosum), cranberry (Vaccinium macrocarpon),
red raspberry (Rubus idaeus), and strawberry (Fragaria ananassa)
are popularly used in the human diet either fresh or in processed
forms. Additionally, there has been a growing trend in the use of
berry extracts as ingredients in functional foods and dietary
supplements, which may be combined with other colorful fruits,
vegetables, and herbal extracts. Extracts of fruits from various
blackberry, raspberry, and gooseberry cultivars act effectively as
free radical inhibitors [3]. Berries provide significant health
benefits because of their high levels of polyphenols, antioxidants,
vitamins, minerals, and fibers [4]. Polyphenols comprise a wide
* Corresponding authors. Tel.: þ82-2450-3739; fax: þ8234365439.
E-mail addresses: [email protected] (S. H. Nile), [email protected]
(S. W. Park).
0899-9007/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.nut.2013.04.007
variety of compounds, divided into several classes like hydroxybenzoic acids, hydroxycinnamic acids, anthocyanins,
proanthocyanidins, flavonols, flavones, flavanols, flavanones,
isoflavones, stilbenes, and lignans that occur in berry fruits. It
has already been demonstrated that a wide diversity of phytochemical levels and antioxidant capacities exist within and
across genera of small fruits [5,6]. Furthermore, accumulating
evidence suggests that genotype has a profound influence on
concentrations of bioactive compounds in berries [7]. Berry
extracts are widely consumed in botanical dietary supplement
forms for their potential human health benefits. Many laboratory
and animal studies have shown that berries have anticancer,
antioxidant, and antiproliferative properties [2,8]. Berry bioactive components impart anticancer effects through various
complementary and overlapping mechanisms of action,
including the induction of metabolizing enzymes, modulation of
gene expression and their effects on cell proliferation, apoptosis,
and subcellular signaling pathways [9]. Some berries, such as
strawberries and black raspberries, have been identified as
sources of phenolic compounds like gallic and ellagic acid, which
have potential cancer chemopreventive activity [10]. These
different bioactive phenolic compounds, including flavonoids,
tannins, and phenolic acids, have received considerable interest
in bearing possible relations to human health. This review
focuses specifically on recent data, related to in vitro and in vivo
studies that have been conducted with berries, emphasizing
the role of phytochemicals. It is noteworthy that recent and
significant advances have been made in understanding the
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
bioavailability and metabolism of phenolic acids and flavonoids
present in berries, which are discussed herein. Studies on the
absorption, metabolism, tissue distribution, in vitro and in vivo
biological effects, and mechanisms of action of berry phenolic
acids and flavonoids are necessary to evaluate their effect on
human health and diseases. In fact, the chemistry and biology of
phenolic acids and flavonoids are important in the context of
their biological effects exerted in the human body.
General chemical composition
Berries contain high levels of a diverse range of phytochemicals, most of which are phenolic molecules. These phytochemicals include a variety of beneficial compounds, such as essential
minerals, vitamins, fatty acids, and dietary fibers. Berries are an
important source of provitamin A, minerals, vitamin C, and Bcomplex vitamins. Berry fruits contain about 15% soluble solids
(mainly sugars) and their high level of fructose makes them
valuable for individuals with diabetes. The high dietary fiber
content is important because fruit pectin acts as an intestinal
regulator [11]. Some of the known chemopreventive agents
present in berries include vitamins A, C, and E, and folic acid;
calcium and selenium; carotene and lutein; phytosterols such as
sitosterol and stigmasterol; triterpene esters; and phenolic
molecules such as anthocyanins, flavonols, flavanols, proanthocyanidins, ellagitannins, and phenolic acids (Fig. 1). The chemistry of berry phenolics directly influences their bioavailability,
metabolism, and biological effects in vivo [12]. The structural
diversity of berry phenolics is observed in several ways including
the following:
1. Their degree of oxidation and the substitution patterns of
hydroxylation,
2. Their abilities to exist as stereoisomers,
3. Glycosylation by sugar moieties and other substituents, and
4. Conjugation to form polymeric molecules such as tannins
and other derived molecules [2,9].
The berry phenolis serve many diverse biological functions
including roles in plant growth, development, and defense. They
provide pigmentation, antimicrobial and antifungal functions,
insect-feeding deterrence, ultraviolet radiation protection,
chelation of toxic heavy metals, and antioxidant quenching of
free radicals generated during photosynthesis [13,14].
Bioactive compounds
Vitamins
Berries contain a large amount of vitamins A, C, and E, and the B
complex vitamins. These vitamins help to boost the immune
system and reduce inflammation. They also are considered antioxidants, which help to fight the effects of oxidative stress leading
to chronic diseases such as heart disease, diabetes, and certain
cancers. Vitamins are highly concentrated in honeyberry and
blackcurrants varieties, which are greater than the concentrations
in strawberries, raspberries, gooseberries [15,16]. Berries are very
important sources of ascorbic acid, which is a water-soluble
compound that fulfills several roles in living systems. It is widely
distributed in fresh fruits and vegetables. The content of vitamin C
in berry fruits is determined by numerous factors, including
species, variety, cultivation, climate, weather conditions, ripeness,
region, storage time, and conditions. Vitamin C is reported in high
135
amounts in blackcurrant and strawberries, which are the richest
source among all the berry fruit species reported [17].
Minerals
Berries are rich in both macro- and micronutrients, among
which honeyberry is a rich source of these minerals. The major
mineral elements found in berries are phosphorus, potassium,
calcium, magnesium, iron, manganese, copper, sodium, and
aluminum. Berries accumulate much iron, calcium, phosphorus,
and sodium minerals from environment and retain leadership
among all other fruiting plants [18]. Mineral nutrients are
scientifically recognized as essential or potentially essential
constituents for human health as they play an important role in
development of bones and teeth and provide strength to muscles
in humans. These major and trace mineral elements are involved
in various important physiological and biochemical processes in
humans by affecting water and electrolyte balance, metabolic
catalysis, oxygen binding, and hormone functions and are
important factors for bone and membrane formation. Table 1
presents the selective mineral content of berries [19].
Anthocyanins
Anthocyanins are a subgroup of flavonoids that are
commonly found in nature. They are widely distributed in fruits
and vegetables, such as blueberries, blackberries, raspberries,
strawberries, blackcurrants, elderberries, grapes, cranberries, red
cabbage, red radishes, and spinach. Anthocyanins are colored
pigments that act as powerful antioxidants; they are especially
abundant in berries with red, blue, or purple pigments. These
colors have been associated with a lower risk for certain cancers,
urinary tract health, improved memory, and normal aging. Along
with fresh berries, a variety of berry products such as juice, wine,
jam, and food colorants (extracted from grape skin, blackcurrants, and other plant materials) contribute significantly to
the intake of anthocyanins [20]. There is considerable current
interest in the possible health effects of anthocyanins in humans
owing to their potential antioxidant effects and their reported
positive effects on blood vessels. More intensive use of berry
anthocyanins as food colorants as well as antioxidants is an
interesting prospect for the food scientist. Anthocyanins are
important in the food industry, being regarded as potential
replacements for synthetic food colorants, and in human nutrition as agents that protect against some diseases [21]. Anthocyanins from berries have extensively been examined for their
effects on mouse model of endotoxin-induced uveitis (EIU) that
shows retinal inflammation, as well as uveitis, by injecting
lipopolysaccharide. Anthocyanin-rich berry extract prevented
the impairment of photoreceptor cell function, as measured by
electroretinogram. At the cellular level, he found that the
EIU-associated rhodopsin decreased and the shortening of
outer segments in photoreceptor cells was suppressed in the
berry extract-treated animals. Moreover, the extract prevented
both STAT3 activation, which induces inflammation-related
rhodopsin decrease, and the increase in interleukin-6 expression, which activates STAT3. In addition to its anti-inflammatory
effect, the anthocyanin-rich berry extract ameliorated the
intracellular elevation of reactive oxygen species (ROS) and
activated nuclear factor-kB, a redox-sensitive transcription
factor. These findings strongly suggest that anthocyanins are
absorbed and display several physiological activities and
health benefits. Oral administration of berry anthocyanins may
be a safe and promising supplement for patients with open angle
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S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
Fig. 1. Bioactive components in berries.
A catechin is a polyphenolic antioxidant found in berries as
a major phytochemical. The most prominent dietary catechins are
catechin, gallocatechin, epicatechin, epigallocatechin, epicatechin
3-gallate, and epigallocatechin 3-gallate. The term catechin also is
commonly used to refer to the related family of flavonoids and the
subgroup flavan-3-ols (or simply flavanols). Catechins are differentiated from the ketone-containing flavonoids such as quercetin
and rutin (flavonols), which support the antioxidant defense
system. Catechins found in caneberries are very similar to those
found in green tea, which may contribute to cancer prevention.
Catechins are more abundant in the external tissues of fruits than
in the internal tissues. Additionally, catechins are more abundant
in the skin than in the remainder of the fruit [22,23].
other berries (raspberries, blackberries, and cranberries) suitable
for potential health benefits. Ellagic acid comprises 51% of the total
phenolic compounds, and it can exist as the free form, as glucosides, or linked as ellagitannins esterified with glucose. Ellagic acid
is of particular interest from a dietary viewpoint as it has been
reported to have antiviral, antioxidant activity, and to provide
protection against cancers of the colon, lung, and esophagus [24].
Ellagic acid is a phenolic compound that is known as a potent
anticarcinogen, antiviral, and antibacterial bioactive compound.
Ellagic acid has been detected in many studies with fruits, nuts, and
berries in which the total ellagic acid concentration was measured
by analyzing the ellagic acid concentration of extracts after acid
hydrolysis. In raspberries, free ellagic acid comprises only a minor
part of the total ellagic acid pool and ellagitannins are the primary
source of ellagic acid released by acid hydrolysis. However,
many other ellagic acid-containing compounds also are present
in raspberries [25,26]. There is a particular interest in ellagic
acid because of evidence of its potential chemopreventive,
anti-inflammatory, antioxidant, and antibacterial effects [27,28].
Ellagic acid
Gallic acid
The presence of bioactive compounds such as flavonoids and
ellagic acid derivatives makes the consumption of strawberries and
Gallic acid is a potent antioxidant found in berries, black tea,
and red wine. It inhibits cell proliferation and cell death in
glaucoma in addition to antiglaucoma medication, whereas
anthocyanin-rich berry extract has a protective effect on visual
function during inflammation [5–10,12].
Catechins
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
137
Table 1
Selective mineral content of berries (amount mg/100 g, edible portion)
Berries
Ca
Fe
P
K
Na
Zn
Mn
Cu
References
15–35
Mg
6–10
0.15–0.60
10–15
56–80
0.11–0.22
0.06–0.12
1.20–3.90
0.03–0.06
[89,99,100]
20–30
17–20
1–2
25–30
100–150
2–4
0.3–0.5
1.2–2.6
0.02–0.04
[90,101,102]
3–5
3–7
0.16–0.40
1–4
24–30
4–6
0.02–0.04
0.3–0.10
0.13–0.20
[91,92,103,104]
15–30
1–05
0.4–0.6
20–22
200–225
0.5–1.0
0.32–0.61
1.5–2.0
Trace
[17,45,93]
1.5–3
3.2–4.5
0.5–0.6
5–8
25–32
1–3
0.33–0.51
0.3–0.6
0.11–0.26
[45,74,94]
35–45
15–18
1.3–2.5
35–40
300–320
1.7–2.5
0.25–0.31
0.35–0.52
0.15–0.20
[95,96,105,106]
Blueberry
Blackberry
Cranberry
Raspberry
Elderberry
Blackcurrant
Ca, calcium; Mg, magnesium; Fe, iron; P, phosphorus; K, potassium; Na, sodium; Zn, zinc; Mn, manganese; Cu, copper
prostate cancer cells. Gallic acid itself has a major antioxidant
activity (Trolox equivalent antioxidant capacity) that is three
times that of vitamin C or E, indicating that its three hydroxyl
groups can function independently as electron acceptors. Its
derivatives, therefore, also are powerful antioxidants with free
hydroxyl groups available for radical scavenging [29]. Gallic acid
has cytotoxic activity in vitro against various cancer cell lines, but
at levels that are unlikely to correspond to plasma concentrations that might be achieved by dietary means. Animal studies
have demonstrated its hepatoprotective effect against carbon
tetrachloride toxicity but at gallic acid levels that could not be
expected in normal human diets. Even heavy and regular
consumers of foods rich in hydroxyl benzoic acids (tea, red wine,
herbs, spices, berries) consume very small amounts of these
substances and it would be hard to increase the dietary burden of
hydroxybenzoic acids because of their strong taste and limited
acceptability to most palates [30].
Quercetin
Quercetin is one of the most abundant flavonoids in fruits
and vegetables. Raspberries contain quercetin glucuronide,
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S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
which has a rich history in folk medicine as a cold and
flu remedy or as a diuretic and antirheumatic. Quercetin is
a potent antioxidant that has additional important biologic,
pharmacologic, and medicinal properties, which inhibits human
platelet aggregation in vitro. It exhibits potential anticancer
properties, the first one by inducing cell differentiation, the
second one, as its glycoside, by inhibiting protein tyrosine
kinase [10,31].
Tannins
Tannins are an important component of berry fruits. In berry
fruits, the largest quantity of condensed tannins with a high
degree of polymerization is found in the chokeberry. Small
quantities of tannins are found in the honeyberry and the
blackberry [32,33]. They comprise both condensed nonhydrolysable tannins, known as proanthocyanidins, and esters of
gallic acid and ellagic acid defined as hydrolysable tannins.
Tannins play an essential role in shaping the sensory properties
of fruit and fruit products. They are responsible for the tart taste
and for changes in the color of fruit and fruit juice [34,35]. The
tart taste results from the interactions among tannins, the
proteins of mucous membranes, and gustatory receptors. As
enzyme inhibitors, tannins decrease the nutritive value of some
plant products. In fruits rich in anthocyanins, tannins stabilize
anthocyanins by binding to them to form copolymers. Most
fruits contain condensed tannins. Hydrolysable tannins (derivatives of gallic and ellagic acids) are less frequently encountered
and have been found in strawberries, raspberries, and blackberries [36,37].
Aroma and volatile compounds
The aroma of the blackberry is one of the major characteristics affecting quality in either fresh or processed fruits. Certainly,
the balance of acid and sugar is directly related to the delicate
flavors in fruits. The volatile compounds responsible for fruit
flavor are biosynthesized through metabolic pathways during
ripening, harvest, postharvest, and storage; they also depend on
many factors related to the species and the type of technological
treatment [38]. Although blackberry has been widely planted,
the study of blackberry flavor is still very limited. The
major volatiles include 2-heptanol, p-cymen-8-ol, 2-heptanone,
1-hexanol, a-terpineol, pulegone, 1-octanol, isoborneol, myrtenol, 4-terpineol, carvone, elemicine, and nonanal. Furfural and its
derivatives were also found to be abundant in some blackberries
[39]. Ethyl 2-methylbutanoate, ethyl 2-methylbutanoate, 2,5dimethyl-4-hydroxy- 3-(2H)-furanone, 2-ethyl-4-hydroxy-5methyl-3-(2H)-furanone, 4-hydroxy-5-methyl-3-(2H)-furanone,
4,5-dimethyl-3- hydroxy-2-(5H)-furanone, and 5-ethyl-3-hydroxy4-methyl-2- (5H)-furanone, dimethyl trisulfide, linalool, and
methional are the major aroma compounds in blackberries [40,41].
The comparative account on total phenolics, flavonoids, and
anthocyanins content of berries (mg/g fresh weight) is given in
Table 2.
Health benefits
From research labs worldwide there is growing evidence
that berries are an important part of a healthy diet. Various
phytochemicals from berries are thought to be antioxidants,
which help to protect the body against various diseases and
disorders and the damaging effects of free radicals, which results
in chronic diseases that are associated with aging. Berries are the
source of many naturally occurring antioxidants, such as various
flavonoids, phenolic acids, and vitamins C and E. The high tannin
content and the resultant antiseptic properties of berries make
them good for tightening tissues as well as treating minor
bleeding. Because berries are rich in antioxidants, they help the
body to fight free radicals and thus to avoid various types of
cancer. The anthocyanins (pigments that account for their
attractive colors) are among the most studied berry phenolics [8,
10]. Anthocyanins have a wide range of bioactivities including
antioxidant, anticancer, and anti-inflammatory properties.
However, advances in tannin/polyphenol research have increased our knowledge of the roles that these large molecules play in
human health [42,43]. In fact, among commonly consumed
berries, blueberries and cranberries contain predominantly
proanthocyanidins, whereas blackberries, black raspberries, red
raspberries, and strawberries contain predominantly ellagitannins. Therefore, the class (and specific chemical structures) of
tannins present in a particular berry type may contribute
significantly to the unique biological properties. For example, the
bacterial anti-adhesive properties observed for the cranberry
appears to be unique among berry fruits. This property is due to
its oligomeric proanthocyanidins, which possess an A-type
structural linkage. Similarly, the distinct biological effects
observed for blueberries (a proanthocyanidin-rich fruit) and
strawberries (an ellagitannin-rich fruit) on neuronal function
and behavior in aging animals may be due to the effects of the
individual classes of tannins in different regions of the brain [44,
45]. Berry phenolics are best known for their ability to act as
antioxidants, but the biological activities exerted by berry
phytochemicals in vivo extend beyond antioxidation. In fact,
a large and growing body of evidence shows that berry phytochemicals regulate the activities of metabolizing enzymes;
modulate nuclear receptors, gene expression, and subcellular
signaling pathways; and repair DNA oxidative damage, and
more. However, berry phenolics are extensively metabolized and
also further converted by the colonic microflora into related
molecules. These compounds may persist in vivo, accumulate in
target tissues, and contribute significantly to the biological
effects that have been observed for berry fruits [46,47]. Raspberries, like blueberries, cranberries, and strawberries contain
a good deal of vitamin C, which is helpful for development of
strong connective tissues and provides protection to the immune
system from attacks of various pathogenic microoganisms.
Raspberry juice is not enough to cure all disorders and diseases
but the bioactive compounds present in the berries play an
important role in preventing many diseases. These substances
include phenolic acids, flavonoids, vitamins, minerals, and
nutrients. The phytochemicals from berries such as raspberries,
cranberries, strawberries, and blueberries contain bioactive
compounds that could prevent infections of microorganisms in
the liver, bladder, or kidney; inflammation; or cancer. Bioactive
compounds from berries could also possibly block the entry of
microorganism by preventing them from adhering to the human
cells that line the walls of the liver, kidneys or urinary tract [48].
Raspberry and its isolated compounds like lutein, vecetin, quercetin, and rutin play an important role for development of
normal vision in human beings. The pigments from raspberries,
cranberries, strawberries, and blueberries are responsible for the
prevention of the development of many types of disorders and
diseases in humans and may be responsible for their blue and red
hue. The berries’ fruits and leaves can be used to relieve sore
mouths, sore throats (soothing), nausea, aphtha, stomatitis,
diabetes, diarrhea, cancer, inflammation, and dysentery [49,50]
(Fig. 2 and Table 3).
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
Table 2
Total phenolics, flavonoids, and anthocyanins content of berries (mg/g fresh
weight)
Berries
Flavonoids Phenolics Anthocyanins References
50
261–585 25–495
[16,89]
276
486
[57,90]
Blueberry
82–326
139
dysfunctions and diseases associated with aging. Although
blueberries themselves are not a cure all, they contain a number
of substances that have health benefits. These substances
include, but are not limited to, fructose, fiber, vitamins, and
antioxidants. Antioxidants thus far seem to have the most
conclusive role in the prevention or delay of cancer, heart
disease, and diseases of the aging process. However, only
a limited number of studies, especially long-term studies of
humans, are available. Blueberries are a source of vitamins,
minerals, dietary fiber, phenolics, and flavonoids. They are very
low in fat and sodium. Research findings by nutritionists from
laboratories worldwide agree that there are health benefits to be
derived by eating raspberries [51,52].
Antioxidant properties
Blackberry
157
315
67–140
[91,92]
44
525
300
[45,93]
6.0
121
99
[74,94]
42
104
45–791
[95,96]
Cranberry
Bilberry
Raspberry
Phytochemicals such as flavonoids and other phenolics may
have antioxidant activity that helps protect cells against the
oxidative damage caused by free radicals. Recently, there has
been increasing attention given to the health benefits of
consuming berries such as blueberries [18]. Antioxidants are
thought to help protect the body against the damaging effects of
free radicals and the chronic diseases associated with the aging
process. Fresh fruits, including blueberries, and vegetables
contain many of these naturally occurring antioxidants such as
anthocyanins, vitamins C and E, which exhibit antioxidant
activity and inhibit low-density lipoprotein (LDL) oxidation [53].
One study reported that blueberries possess considerably high
antioxidant activity that is attributed in part to their anthocyanin
content [54]. Other studies have assessed the antioxidant activity
of berries, including black and red raspberries, by measuring the
superoxide scavenging activity [55]. Extracts of berries of several
cultivars of blackberries, black and red currants, blueberries, and
black and red raspberries showed a remarkably high scavenging
activity toward chemically generated superoxide radicals [56].
Blackcurrants were highly active toward xanthine oxidase,
possibly due to their high anthocyanin and polyphenol content.
By using an artificial peroxyl radical model system, the extract of
fresh strawberries had a greater total antioxidant capacity than
extracts of plum, orange, red grape, kiwi fruit, pink grapefruit,
white grape, banana, apple, tomato, pear, and honeydew
melon. Strawberry, thorn-less blackberry, and red and black
raspberry have high oxygen radical absorbance activity against
peroxyl radicals. Antioxidant activities can vary among berry
cultivars [57].
Anticancer properties
Elderberry
46
29–60
44
[97,98]
Blackcurrant
Nutrition and aging
Berries, along with other colorful fruits and vegetables, test
high in their ability to subdue free radicals. These free radicals,
which can damage cell membranes and DNA through a process
known as oxidative stress, are blamed for many of the
Numerous in vitro studies have demonstrated activity of
various berry extracts against different aspects of the tumorigenic process and proved that the diets high in fruits and vegetables protect against cancer. Epidemiologic studies suggest that
consumption of a phytochemical-rich diet, which includes fruits
and vegetables, contributes toward reducing the risk for certain
types of human cancers [51]. Berry bioactive phenolics impart
anticancer effects through various complementary and overlapping mechanisms of action including the induction of
metabolizing enzymes; modulation of gene expression; and
their effects on cell proliferation, apoptosis, and subcellular
signaling pathways. A large number of laboratory and animal
studies have shown that berries have anticancer properties [58].
The anthocyanins present in blackberries and raspberries are
important for the beneficial health effects associated with
their antioxidant, anti-inflammatory, and chemopreventative
140
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
Fig. 2. Berry phenolics and flavonoids and their biological activities.
properties; the biological activity of black raspberry against
esophageal, colon, and oral cancers has been demonstrated. It
has long been established that cyanidin-3-glucoside and cyanidin-3-rutinoside are the respective major and minor anthocyanins in blackberries [2,59]. In addition to anthocyanins, these
fruits are also a rich natural source of other chemopreventative
phytochemicals such as flavonols, phenolic acids, ellagic acid,
vitamins C and E, folic acid, and b-sitosterol. It is not uncommon
for fruits or any other plant material of related species to
demonstrate varying degrees of biological activities ranging from
some species being totally inactive to others exhibiting exceptional activity [60].
Antimutagenic properties
Several chemical species from berry extracts have been isolated and found to possess antimutagenic activity, which block
cancer cell metabolism or kill cancer cells in culture, inactivate
free radicals and active oxygen species, exhibit antiestrogenic
activity, and inhibit mutagenesis. The most intensively studied
antimutagenic agents are the ellagitannins, especially ellagic acid
[61,62]. The anticarcinogenic and anti-inflammatory effects of
fruits and berries have been well documented. Several plant
extracts inhibit the replication of cancer cells in culture, and
many plant compounds are highly effective in pure form, the
most thoroughly studied of these being from black raspberries
and resveratrol [63,64]. The researchers reported that the
extracts from raspberries, strawberries, and blueberries to inactivate mutagenesis by benzo[a] pyrene and cause suppression by
blackberries for mutagenesis by 2-amino anthracene and found
the magnitude of the effect to vary with the variety of berries
grown in the same orchard under identical conditions [65,66].
The inactivation of metabolically activated carcinogens is
caused by components of the berry extracts that inhibit the
cytochrome P450 system responsible for converting carcinogenic
compounds into forms capable of covalent binding with DNA.
Less understood is the ability of blackberry extracts to inhibit
ultraviolet-induced mutagenesis [67]. In addition to their effects
on mutagenesis, raspberries, blackberries, and muscadine grapes
almost completely inhibit the activity of the matrix metalloproteinases 2 and 9 involved in the invasion and metastasis of
cancer cells. Although antioxidants can clearly protect cells from
mutagenesis at the initiation stage of carcinogenesis, their role in
the destruction of transformed cells is less clear [68]. Boivin and
others (2007) measured the antioxidant activity and antiproliferative activities of berries and found red raspberries to be
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
141
Table 3
Comparative account on bioactive components and biological properties of berries
Berries
Phytochemicals
Biological Properties
References
Blueberry
High in antioxidants, vitamin C, B
complex, E, and A
High in selenium, zinc, iron, and
manganese. Contains b-carotene,
lutein, and zeaxanthin
Anticancer, anti-inflammatory, anti-diabetic. Prevents weight
loss, macular degeneration. Helps prevent Alzheimer’s disease;
reverses signs of aging; protects and enhances circulation;
reduces cholesterol.
[99,100]
Blackberry
High in antioxidants, polyphenols,
manganese, folate, fibers, cyaniding3-O-glucoside, and vitamin C.
Contains salicylate and high tannin.
Fights free radical damage; antiseptic, antibacterial/viral, anticancer;
reduces cholesterol; delays process of aging; is an analgesic and
pain reliever; provides strength to blood vessels.
[101,102]
Cranberry
High in vitamins C, A, calcium, iron,
folate, magnesium, and manganese.
Contains higher percentage of
phenolics than other berries studied.
Antibacterial, antiseptic, and diuretic; aids digestion; removes fats
from lymphatic system; and promotes cardiovascular health.
[103,104]
Good for eyes, mouth, and gum health. Provides strength; powerful
Bilberry
anti-inflammatory; protects blood vessels and strengthens arteries;
High in anthocyanins, flavonols.
High in vitamins C, E, and manganese. and improves circulation.
Contains carotenoid, lutein, and
zeaxanthin.
[17,45]
Anticancer; prevents free radical damage; antimicrobial; and increases [17,45]
Raspberry
Rich in vitamins C, B, u-3, fibers, gallic metabolic rate, which burns fats. Great for eye health and strength.
acid, ellagic acid, and acts as a strong
antioxidant.
Contains folate, iron, potassium,
copper, and lutein.
Elderberry
Rich in vitamins C, A, and B.
Contains high amounts of
flavonoids and carotenoids.
High in calcium and iron.
Protects DNA damage from free radicals; aids in arthritic conditions;
improves respiration and asthma; boosts immune system; and
stimulates digestive system.
[105,106]
Blackcurrant
High in anthocyanins, calcium, zinc,
magnesium, potassium, vitamins A,
B2, and gibberellic acids.
Anti-inflammatory, cleans and reduces blood cholesterol; stimulates
digestion, the liver, pancreas, spleen, and kidneys.
[75,107]
among the most effective in blocking proliferation of different
types of cancer cells. However, they found no correlation
between antioxidant activity and the ability to inhibit cancer cell
replication [60]. Likewise, Liu and others (2002) found no
correlation between antioxidant activity and antiproliferative
activity when comparing four different varieties of raspberries.
In addition to its antioxidant effect, each extract also contains
numerous compounds that can affect cell survival and replication by interacting with different replicative and metabolic
pathways [69].
Antimicrobial properties
Certain berries rich in tannins have been found to increase
bacterial infections. Two different types of polymeric tannins in
these berries protect against pathogenic bacteria. Presence of the
A-type linkage of cranberry (Vaccinium macrocarpon) proanthocyanidins may enhance both in vitro and urinary bacterial antiadhesion activities [70]. Additionally, other tannin-containing
berries may contribute to this effect, as berry juices of a mixture
of cranberries (Vaccinium oxycoccus) and lingonberries as well as
142
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
cloudberry juice protect against urinary tract infection [71,72].
Among the berries, cranberries, cloudberries, red raspberries,
strawberries, and bilberries possess clear antimicrobial effects
against human pathogens. Berry ellagitannins are strong antimicrobial agents acting as possible anti-adherence compounds in
preventing the colonization and infection of many pathogens [34,
35]. The phenolic extract of cloudberry, which is comprised
primarily of ellagitannins, has the strongest antimicrobial effect,
followed by red raspberry and strawberry. Salmonella spp.,
Staphylococcus spp., Helicobacter spp., and Bacillus spp. are the
bacteria that are most sensitive to berry phenolics. Additionally,
the growth of Escherichia spp., Clostridium spp., and Campylobacter spp., but not the growth of Lactobacillus spp. and Listeria
spp., is inhibited by berry phenolics [41,73]. Red raspberry
phenolics and its ellagitannin fraction also have powerful antimicrobial properties against the growth of human colonial
pathogens, Klebsiella oxytoca and Proteus mirabilis [74]. Several
mechanisms of action in the inhibition of bacteria are involved,
such as destabilization of cytoplasmic membrane, permeabilization of plasma membrane, inhibition of extracellular microbial
enzymes, direct actions on microbial metabolism, and deprivation of the substrates required for microbial growth [34,35]. The
berry extracts inhibited the growth primarily of gram-negative
bacteria but had no effect on gram-positive bacteria. However,
there is very little information about the antimicrobial capacity of
phenolics present in berries, except in cranberry. Extracts of the
aerial parts of bearberry and lingonberry were active against the
gram-negative bacteria E. coli and P. vulgaris. The activity is known
to be due to the phenolic glycosides arbutin and metylarbutin.
Cloudberry, raspberry, and strawberry extracts were the strongest inhibitors of gram-negative bacteria, especially Typhimurium
[73,75]. Ellagic acid inhibits a range of pathogenic organisms
including Vibrio cholerae, Shigella dysenteriae, and Campylobacter
spp. It can be hypothesized that ellagitannins could be one of
the components in cloudberries, raspberries, and strawberries
causing the inhibition against Salmonella. The antimicrobial
effects of berry extracts against gram-negative bacteria decreased
in the following order: cloudberry > raspberry > strawberry >
lingonberry > blueberry > cranberry > sea buckthorn berry >
blackcurrant [41,76].
Anti-inflammatory properties
There are many health benefits of consuming berries, such as
blueberries that contain anthocyanins, the flavonoid pigment
responsible for their red to bluish hue. Anthocyanins exhibit
antioxidant activity and inhibit oxidation of LDL. They also have
vasoprotective and anti-inflammatory activity. Anthocyanin-rich
extracts from European berries such as the bilberry (Vaccinium
myrtillus) have been sold commercially to treat microcirculation
disease and to maintain normal vascular permeability [77].
Extensive pharmacologic and clinical studies have demonstrated
that flavonoids are the active substances that are largely
responsible for the action of the drug. The main pharmacologic
activities of berries are primarily cardiovascular ones, including
cardiotonic, antiarrithythmic, hypotensive, and hypolipidemic
effects [78]. Raspberry phytochemicals beneficially modulate
enzyme activity, cellular pathways, and gene expression. In
addition to reducing oxidized-LDL formation via their antioxidant
activity, raspberry phytochemicals have demonstrated antiatherosclerotic and anti-inflammatory activities, which may
provide protection against cardiovascular diseases [79]. Many
studies have demonstrated the ability of raspberry phytochemicals to reduce cancer cell growth in vitro. Anthocyanins have the
ability to down-regulate cyclooxygenase-2 expression and
enzyme activity, a mechanism for its antiproliferative actions on
many different human cancer cell lines [31,80]. In contrast, ellagic
acid’s mechanism for its antiproliferative actions across many
different human cancer cell lines is via induction of apoptosis.
Despite the antiproliferative activities of both anthocyanin and
ellagic acid, it is the ellagitannin fractions that mostly account for
this biological effect by red raspberry extracts. In vitro studies also
have found phytochemicals from black raspberry extracts to be
effective in reducing vascular endothelial growth factor expression, a promoter of angiogenesis, which is a critical step for tumor
metastasis [81,82].
Neuroprotective properties
Foods and food ingredients, in particular components chemically classified as antioxidants, have been reported to exert
a beneficial effect in neurodegeneration. In the developed world,
life expectancy is increasing, with a concomitant increased
incidence of many age-related diseases, such as cancer, cardiovascular troubles, and neurodegeneration [83,84]. Substantial
evidence supports the hypothesis that oxidative stress plays
a major role in the pathogenesis of neurodegenerative disease.
Oxidative stress is generally caused by the excessive accumulation of ROS in cells and has been implicated in the development
of many neurodegenerative diseases, including Parkinson’s
disease, Huntington’s disease, amyotrophic lateral sclerosis, and
Alzheimer’s disease [85,86]. Behavioral studies in rodents have
revealed an attenuation of brain aging when strawberries,
blueberries, or blackberries are ingested. Evidence is increasing
that these phytochemicals, and by association the foods, have
beneficial effects on human health and reduce the risk of
cardiovascular disease and type 2 diabetes [87,88].
Conclusion
This review demonstrates that a number of in vitro and
in vivo studies, using cell cultures of animal and human cells,
have suggested that bioactive compounds of berries positively
show an effect on human health. The presented characteristics of
various berry fruits point to vast differences in the type of their
bioactive compounds; such differences are observed with regard
to both the content and the qualitative composition of those
compounds. The most significant health benefits are ascribed to
phenolic compounds and vitamin C, which result mostly from
antioxidant, anticancer, antimutagenic, antimicrobial, antiinflammatory, and neuroprotective properties. The use of all
these biological activities presented in this review related to
berry bioactive phenolics and flavonoids might promote the
development of alternative berry compounds for the prevention
and control of various diseases and disorders. This issue will be
critical for future research priorities that may offer numerous
opportunities for berries to be used in the food industry and
medicine and will provide a wide range of health benefits.
Further research is needed on this subject regarding the issues
related to plant breeding and genetic approaches at the interface
with the synthesis of compounds for nutrition and health
purposes should receive more emphasis and attention.
Acknowledgments
This work was supported by a grant from Bio-Green 21
Program (No. PJ009074), Rural Development Administration,
Republic of Korea.
S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144
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