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Nutrition 30 (2014) 134–144

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Nutrition

journal homepage: www.nutr i t ionjrnl .com

Review

Edible berries: Bioactive components and their effecton 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

Article history:Received 14 March 2013Accepted 11 April 2013

Keywords:PhytochemicalsHuman healthBlueberriesBlackberriesRaspberriesStrawberries

* Corresponding authors. Tel.: þ82-2450-3739; faxE-mail addresses: nileshivraj@gmail.com (S. H. Nil

(S. W. Park).

0899-9007/$ - see front matter � 2014 Elsevier Inc. Ahttp://dx.doi.org/10.1016/j.nut.2013.04.007

a b s t r a c t

The importance of food consumption in relation to human health has increased consumer atten-tion in nutraceutical components and foods, especially fruits and vegetables. Berries are a richsource 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 compoundssuch as sugars, essential oils, carotenoids, vitamins, and minerals. Bioactive compounds fromberries have potent antioxidant, anticancer, antimutagenic, antimicrobial, anti-inflammatory, andantineurodegenerative properties, both in vitro and in vivo. The following is a comprehensive andcritical review on nutritional and non-nutritional bioactive compounds of berries including theirabsorption, metabolism, and biological activity in relation to their potential effect on humanhealth.

� 2014 Elsevier Inc. All rights reserved.

Introduction variety of compounds, divided into several classes like hy-

Increased consumption of fruits and vegetables is recom-mended in dietary guidelines worldwide and the intake of fruitslike berries which are rich in nutrients and phytochemicalscan prevent various diseases and disorders. Most berries aredelicious and powerful disease-fighting foods and make up thelargest proportion of fruit that is consumed in the human diet[1]. Berry fruits are popularly consumed not only in fresh andfrozen forms but also as processed and derived products,including dried and canned fruits, yogurts, beverages, jams, andjellies [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 processedforms. Additionally, there has been a growing trend in the use ofberry extracts as ingredients in functional foods and dietarysupplements, which may be combined with other colorful fruits,vegetables, and herbal extracts. Extracts of fruits from variousblackberry, raspberry, and gooseberry cultivars act effectively asfree radical inhibitors [3]. Berries provide significant healthbenefits because of their high levels of polyphenols, antioxidants,vitamins, minerals, and fibers [4]. Polyphenols comprise a wide

: þ8234365439.e), sewpark@konkuk.ac.kr

ll rights reserved.

droxybenzoic acids, hydroxycinnamic acids, anthocyanins,proanthocyanidins, flavonols, flavones, flavanols, flavanones,isoflavones, stilbenes, and lignans that occur in berry fruits. Ithas already been demonstrated that a wide diversity of phyto-chemical levels and antioxidant capacities exist within andacross genera of small fruits [5,6]. Furthermore, accumulatingevidence suggests that genotype has a profound influence onconcentrations of bioactive compounds in berries [7]. Berryextracts are widely consumed in botanical dietary supplementforms for their potential human health benefits. Many laboratoryand animal studies have shown that berries have anticancer,antioxidant, and antiproliferative properties [2,8]. Berry bioac-tive components impart anticancer effects through variouscomplementary and overlapping mechanisms of action,including the induction of metabolizing enzymes, modulation ofgene expression and their effects on cell proliferation, apoptosis,and subcellular signaling pathways [9]. Some berries, such asstrawberries and black raspberries, have been identified assources of phenolic compounds like gallic and ellagic acid, whichhave potential cancer chemopreventive activity [10]. Thesedifferent bioactive phenolic compounds, including flavonoids,tannins, and phenolic acids, have received considerable interestin bearing possible relations to human health. This reviewfocuses specifically on recent data, related to in vitro and in vivostudies that have been conducted with berries, emphasizingthe role of phytochemicals. It is noteworthy that recent andsignificant advances have been made in understanding the

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bioavailability and metabolism of phenolic acids and flavonoidspresent in berries, which are discussed herein. Studies on theabsorption, metabolism, tissue distribution, in vitro and in vivobiological effects, and mechanisms of action of berry phenolicacids and flavonoids are necessary to evaluate their effect onhuman health and diseases. In fact, the chemistry and biology ofphenolic acids and flavonoids are important in the context oftheir biological effects exerted in the human body.

General chemical composition

Berries contain high levels of a diverse range of phytochem-icals, most of which are phenolic molecules. These phytochem-icals include a variety of beneficial compounds, such as essentialminerals, vitamins, fatty acids, and dietary fibers. Berries are animportant source of provitamin A, minerals, vitamin C, and B-complex vitamins. Berry fruits contain about 15% soluble solids(mainly sugars) and their high level of fructose makes themvaluable for individuals with diabetes. The high dietary fibercontent is important because fruit pectin acts as an intestinalregulator [11]. Some of the known chemopreventive agentspresent in berries include vitamins A, C, and E, and folic acid;calcium and selenium; carotene and lutein; phytosterols such assitosterol and stigmasterol; triterpene esters; and phenolicmolecules such as anthocyanins, flavonols, flavanols, proantho-cyanidins, ellagitannins, and phenolic acids (Fig. 1). The chem-istry of berry phenolics directly influences their bioavailability,metabolism, and biological effects in vivo [12]. The structuraldiversity of berry phenolics is observed in several ways includingthe following:

1. Their degree of oxidation and the substitution patterns ofhydroxylation,

2. Their abilities to exist as stereoisomers,3. Glycosylation by sugar moieties and other substituents, and4. Conjugation to form polymeric molecules such as tannins

and other derived molecules [2,9].

The berry phenolis serve many diverse biological functionsincluding roles in plant growth, development, and defense. Theyprovide pigmentation, antimicrobial and antifungal functions,insect-feeding deterrence, ultraviolet radiation protection,chelation of toxic heavy metals, and antioxidant quenching offree radicals generated during photosynthesis [13,14].

Bioactive compounds

Vitamins

Berries contain a large amount of vitaminsA, C, andE, and theBcomplex vitamins. These vitamins help to boost the immunesystem and reduce inflammation. They also are considered anti-oxidants, which help to fight the effects of oxidative stress leadingto chronic diseases such as heart disease, diabetes, and certaincancers. Vitamins are highly concentrated in honeyberry andblackcurrants varieties, which are greater than the concentrationsin strawberries, raspberries, gooseberries [15,16]. Berries are veryimportant sources of ascorbic acid, which is a water-solublecompound that fulfills several roles in living systems. It is widelydistributed in fresh fruits and vegetables. The content of vitamin Cin berry fruits is determined by numerous factors, includingspecies, variety, cultivation, climate,weather conditions, ripeness,region, storage time, and conditions. Vitamin C is reported in high

amounts in blackcurrant and strawberries, which are the richestsource among all the berry fruit species reported [17].

Minerals

Berries are rich in both macro- and micronutrients, amongwhich honeyberry is a rich source of these minerals. The majormineral elements found in berries are phosphorus, potassium,calcium, magnesium, iron, manganese, copper, sodium, andaluminum. Berries accumulate much iron, calcium, phosphorus,and sodium minerals from environment and retain leadershipamong all other fruiting plants [18]. Mineral nutrients arescientifically recognized as essential or potentially essentialconstituents for human health as they play an important role indevelopment of bones and teeth and provide strength tomusclesin humans. These major and trace mineral elements are involvedin various important physiological and biochemical processes inhumans by affecting water and electrolyte balance, metaboliccatalysis, oxygen binding, and hormone functions and areimportant factors for bone and membrane formation. Table 1presents the selective mineral content of berries [19].

Anthocyanins

Anthocyanins are a subgroup of flavonoids that arecommonly found in nature. They are widely distributed in fruitsand vegetables, such as blueberries, blackberries, raspberries,strawberries, blackcurrants, elderberries, grapes, cranberries, redcabbage, red radishes, and spinach. Anthocyanins are coloredpigments that act as powerful antioxidants; they are especiallyabundant in berries with red, blue, or purple pigments. Thesecolors have been associated with a lower risk for certain cancers,urinary tract health, improvedmemory, and normal aging. Alongwith fresh berries, a variety of berry products such as juice, wine,jam, and food colorants (extracted from grape skin, black-currants, and other plant materials) contribute significantly tothe intake of anthocyanins [20]. There is considerable currentinterest in the possible health effects of anthocyanins in humansowing to their potential antioxidant effects and their reportedpositive effects on blood vessels. More intensive use of berryanthocyanins as food colorants as well as antioxidants is aninteresting prospect for the food scientist. Anthocyanins areimportant in the food industry, being regarded as potentialreplacements for synthetic food colorants, and in human nutri-tion as agents that protect against some diseases [21]. Antho-cyanins from berries have extensively been examined for theireffects on mouse model of endotoxin-induced uveitis (EIU) thatshows retinal inflammation, as well as uveitis, by injectinglipopolysaccharide. Anthocyanin-rich berry extract preventedthe impairment of photoreceptor cell function, as measured byelectroretinogram. At the cellular level, he found that theEIU-associated rhodopsin decreased and the shortening ofouter segments in photoreceptor cells was suppressed in theberry extract-treated animals. Moreover, the extract preventedboth STAT3 activation, which induces inflammation-relatedrhodopsin decrease, and the increase in interleukin-6 expres-sion, which activates STAT3. In addition to its anti-inflammatoryeffect, the anthocyanin-rich berry extract ameliorated theintracellular elevation of reactive oxygen species (ROS) andactivated nuclear factor-kB, a redox-sensitive transcriptionfactor. These findings strongly suggest that anthocyanins areabsorbed and display several physiological activities andhealth benefits. Oral administration of berry anthocyanins maybe a safe and promising supplement for patients with open angle

Fig. 1. Bioactive components in berries.

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glaucoma in addition to antiglaucoma medication, whereasanthocyanin-rich berry extract has a protective effect on visualfunction during inflammation [5–10,12].

Catechins

A catechin is a polyphenolic antioxidant found in berries asamajor phytochemical. Themost prominent dietary catechins arecatechin, gallocatechin, epicatechin, epigallocatechin, epicatechin3-gallate, and epigallocatechin 3-gallate. The term catechin also iscommonly used to refer to the related family of flavonoids and thesubgroup flavan-3-ols (or simply flavanols). Catechins are differ-entiated from the ketone-containing flavonoids such as quercetinand rutin (flavonols), which support the antioxidant defensesystem. Catechins found in caneberries are very similar to thosefound in green tea, which may contribute to cancer prevention.Catechins are more abundant in the external tissues of fruits thanin the internal tissues. Additionally, catechins are more abundantin the skin than in the remainder of the fruit [22,23].

Ellagic acid

The presence of bioactive compounds such as flavonoids andellagicacidderivativesmakes theconsumptionof strawberriesand

other berries (raspberries, blackberries, and cranberries) suitablefor potential health benefits. Ellagic acid comprises 51% of the totalphenolic compounds, and it can exist as the free form, as gluco-sides, or linked as ellagitannins esterifiedwith glucose. Ellagic acidis of particular interest from a dietary viewpoint as it has beenreported to have antiviral, antioxidant activity, and to provideprotection against cancers of the colon, lung, and esophagus [24].Ellagic acid is a phenolic compound that is known as a potentanticarcinogen, antiviral, and antibacterial bioactive compound.Ellagic acidhasbeendetected inmanystudieswith fruits, nuts, andberries inwhich the total ellagic acid concentrationwasmeasuredby analyzing the ellagic acid concentration of extracts after acidhydrolysis. In raspberries, free ellagic acid comprises only a minorpart of the total ellagic acid pool and ellagitannins are the primarysource of ellagic acid released by acid hydrolysis. However,many other ellagic acid-containing compounds also are presentin raspberries [25,26]. There is a particular interest in ellagicacid because of evidence of its potential chemopreventive,anti-inflammatory, antioxidant, and antibacterial effects [27,28].

Gallic acid

Gallic acid is a potent antioxidant found in berries, black tea,and red wine. It inhibits cell proliferation and cell death in

Table 1Selective mineral content of berries (amount mg/100 g, edible portion)

Berries Ca Mg Fe P K Na Zn Mn Cu References

Blueberry

15–35 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]

Blackberry

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]

Cranberry

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]

Raspberry

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]

Elderberry

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]

Blackcurrant

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]

Ca, calcium; Mg, magnesium; Fe, iron; P, phosphorus; K, potassium; Na, sodium; Zn, zinc; Mn, manganese; Cu, copper

S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144 137

prostate cancer cells. Gallic acid itself has a major antioxidantactivity (Trolox equivalent antioxidant capacity) that is threetimes that of vitamin C or E, indicating that its three hydroxylgroups can function independently as electron acceptors. Itsderivatives, therefore, also are powerful antioxidants with freehydroxyl groups available for radical scavenging [29]. Gallic acidhas cytotoxic activity in vitro against various cancer cell lines, butat levels that are unlikely to correspond to plasma concentra-tions that might be achieved by dietary means. Animal studieshave demonstrated its hepatoprotective effect against carbontetrachloride toxicity but at gallic acid levels that could not be

expected in normal human diets. Even heavy and regularconsumers of foods rich in hydroxyl benzoic acids (tea, red wine,herbs, spices, berries) consume very small amounts of thesesubstances and it would be hard to increase the dietary burden ofhydroxybenzoic acids because of their strong taste and limitedacceptability to most palates [30].

Quercetin

Quercetin is one of the most abundant flavonoids in fruitsand vegetables. Raspberries contain quercetin glucuronide,

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which has a rich history in folk medicine as a cold andflu remedy or as a diuretic and antirheumatic. Quercetin isa potent antioxidant that has additional important biologic,pharmacologic, and medicinal properties, which inhibits humanplatelet aggregation in vitro. It exhibits potential anticancerproperties, the first one by inducing cell differentiation, thesecond one, as its glycoside, by inhibiting protein tyrosinekinase [10,31].

Tannins

Tannins are an important component of berry fruits. In berryfruits, the largest quantity of condensed tannins with a highdegree of polymerization is found in the chokeberry. Smallquantities of tannins are found in the honeyberry and theblackberry [32,33]. They comprise both condensed non-hydrolysable tannins, known as proanthocyanidins, and esters ofgallic acid and ellagic acid defined as hydrolysable tannins.Tannins play an essential role in shaping the sensory propertiesof fruit and fruit products. They are responsible for the tart tasteand for changes in the color of fruit and fruit juice [34,35]. Thetart taste results from the interactions among tannins, theproteins of mucous membranes, and gustatory receptors. Asenzyme inhibitors, tannins decrease the nutritive value of someplant products. In fruits rich in anthocyanins, tannins stabilizeanthocyanins by binding to them to form copolymers. Mostfruits contain condensed tannins. Hydrolysable tannins (deriva-tives of gallic and ellagic acids) are less frequently encounteredand have been found in strawberries, raspberries, and black-berries [36,37].

Aroma and volatile compounds

The aroma of the blackberry is one of the major characteris-tics affecting quality in either fresh or processed fruits. Certainly,the balance of acid and sugar is directly related to the delicateflavors in fruits. The volatile compounds responsible for fruitflavor are biosynthesized through metabolic pathways duringripening, harvest, postharvest, and storage; they also depend onmany factors related to the species and the type of technologicaltreatment [38]. Although blackberry has been widely planted,the study of blackberry flavor is still very limited. Themajor volatiles include 2-heptanol, p-cymen-8-ol, 2-heptanone,1-hexanol, a-terpineol, pulegone, 1-octanol, isoborneol, myrte-nol, 4-terpineol, carvone, elemicine, and nonanal. Furfural and itsderivatives were also found to be abundant in some blackberries[39]. Ethyl 2-methylbutanoate, ethyl 2-methylbutanoate, 2,5-dimethyl-4-hydroxy- 3-(2H)-furanone, 2-ethyl-4-hydroxy-5-methyl-3-(2H)-furanone, 4-hydroxy-5-methyl-3-(2H)-furanone,4,5-dimethyl-3- hydroxy-2-(5H)-furanone, and 5-ethyl-3-hydroxy-4-methyl-2- (5H)-furanone, dimethyl trisulfide, linalool, andmethional are themajor aroma compounds in blackberries [40,41].The comparative account on total phenolics, flavonoids, andanthocyanins content of berries (mg/g fresh weight) is given inTable 2.

Health benefits

From research labs worldwide there is growing evidencethat berries are an important part of a healthy diet. Variousphytochemicals from berries are thought to be antioxidants,which help to protect the body against various diseases anddisorders and the damaging effects of free radicals, which resultsin chronic diseases that are associated with aging. Berries are the

source of many naturally occurring antioxidants, such as variousflavonoids, phenolic acids, and vitamins C and E. The high tannincontent and the resultant antiseptic properties of berries makethem good for tightening tissues as well as treating minorbleeding. Because berries are rich in antioxidants, they help thebody to fight free radicals and thus to avoid various types ofcancer. The anthocyanins (pigments that account for theirattractive colors) are among the most studied berry phenolics [8,10]. Anthocyanins have a wide range of bioactivities includingantioxidant, anticancer, and anti-inflammatory properties.However, advances in tannin/polyphenol research have increa-sed our knowledge of the roles that these large molecules play inhuman health [42,43]. In fact, among commonly consumedberries, blueberries and cranberries contain predominantlyproanthocyanidins, whereas blackberries, black raspberries, redraspberries, and strawberries contain predominantly ellagi-tannins. Therefore, the class (and specific chemical structures) oftannins present in a particular berry type may contributesignificantly to the unique biological properties. For example, thebacterial anti-adhesive properties observed for the cranberryappears to be unique among berry fruits. This property is due toits oligomeric proanthocyanidins, which possess an A-typestructural linkage. Similarly, the distinct biological effectsobserved for blueberries (a proanthocyanidin-rich fruit) andstrawberries (an ellagitannin-rich fruit) on neuronal functionand behavior in aging animals may be due to the effects of theindividual classes of tannins in different regions of the brain [44,45]. Berry phenolics are best known for their ability to act asantioxidants, but the biological activities exerted by berryphytochemicals in vivo extend beyond antioxidation. In fact,a large and growing body of evidence shows that berry phyto-chemicals regulate the activities of metabolizing enzymes;modulate nuclear receptors, gene expression, and subcellularsignaling pathways; and repair DNA oxidative damage, andmore. However, berry phenolics are extensively metabolized andalso further converted by the colonic microflora into relatedmolecules. These compounds may persist in vivo, accumulate intarget tissues, and contribute significantly to the biologicaleffects that have been observed for berry fruits [46,47]. Rasp-berries, like blueberries, cranberries, and strawberries containa good deal of vitamin C, which is helpful for development ofstrong connective tissues and provides protection to the immunesystem from attacks of various pathogenic microoganisms.Raspberry juice is not enough to cure all disorders and diseasesbut the bioactive compounds present in the berries play animportant role in preventing many diseases. These substancesinclude phenolic acids, flavonoids, vitamins, minerals, andnutrients. The phytochemicals from berries such as raspberries,cranberries, strawberries, and blueberries contain bioactivecompounds that could prevent infections of microorganisms inthe liver, bladder, or kidney; inflammation; or cancer. Bioactivecompounds from berries could also possibly block the entry ofmicroorganism by preventing them from adhering to the humancells that line the walls of the liver, kidneys or urinary tract [48].Raspberry and its isolated compounds like lutein, vecetin, quer-cetin, and rutin play an important role for development ofnormal vision in human beings. The pigments from raspberries,cranberries, strawberries, and blueberries are responsible for theprevention of the development of many types of disorders anddiseases in humans andmay be responsible for their blue and redhue. The berries’ fruits and leaves can be used to relieve soremouths, sore throats (soothing), nausea, aphtha, stomatitis,diabetes, diarrhea, cancer, inflammation, and dysentery [49,50](Fig. 2 and Table 3).

Table 2Total phenolics, flavonoids, and anthocyanins content of berries (mg/g freshweight)

Berries Flavonoids Phenolics Anthocyanins References

Blueberry

50 261–585 25–495 [16,89]

Blackberry

276 486 82–326 [57,90]

Cranberry

157 315 67–140 [91,92]

Bilberry

44 525 300 [45,93]

Raspberry

6.0 121 99 [74,94]

Elderberry

42 104 45–791 [95,96]

Blackcurrant

46 29–60 44 [97,98]

S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144 139

Nutrition and aging

Berries, along with other colorful fruits and vegetables, testhigh in their ability to subdue free radicals. These free radicals,which can damage cell membranes and DNA through a processknown as oxidative stress, are blamed for many of the

dysfunctions and diseases associated with aging. Althoughblueberries themselves are not a cure all, they contain a numberof substances that have health benefits. These substancesinclude, but are not limited to, fructose, fiber, vitamins, andantioxidants. Antioxidants thus far seem to have the mostconclusive role in the prevention or delay of cancer, heartdisease, and diseases of the aging process. However, onlya limited number of studies, especially long-term studies ofhumans, are available. Blueberries are a source of vitamins,minerals, dietary fiber, phenolics, and flavonoids. They are verylow in fat and sodium. Research findings by nutritionists fromlaboratories worldwide agree that there are health benefits to bederived by eating raspberries [51,52].

Antioxidant properties

Phytochemicals such as flavonoids and other phenolics mayhave antioxidant activity that helps protect cells against theoxidative damage caused by free radicals. Recently, there hasbeen increasing attention given to the health benefits ofconsuming berries such as blueberries [18]. Antioxidants arethought to help protect the body against the damaging effects offree radicals and the chronic diseases associated with the agingprocess. Fresh fruits, including blueberries, and vegetablescontain many of these naturally occurring antioxidants such asanthocyanins, vitamins C and E, which exhibit antioxidantactivity and inhibit low-density lipoprotein (LDL) oxidation [53].One study reported that blueberries possess considerably highantioxidant activity that is attributed in part to their anthocyanincontent [54]. Other studies have assessed the antioxidant activityof berries, including black and red raspberries, by measuring thesuperoxide scavenging activity [55]. Extracts of berries of severalcultivars of blackberries, black and red currants, blueberries, andblack and red raspberries showed a remarkably high scavengingactivity 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 offresh strawberries had a greater total antioxidant capacity thanextracts of plum, orange, red grape, kiwi fruit, pink grapefruit,white grape, banana, apple, tomato, pear, and honeydewmelon. Strawberry, thorn-less blackberry, and red and blackraspberry have high oxygen radical absorbance activity againstperoxyl radicals. Antioxidant activities can vary among berrycultivars [57].

Anticancer properties

Numerous in vitro studies have demonstrated activity ofvarious berry extracts against different aspects of the tumori-genic process and proved that the diets high in fruits and vege-tables protect against cancer. Epidemiologic studies suggest thatconsumption of a phytochemical-rich diet, which includes fruitsand vegetables, contributes toward reducing the risk for certaintypes of human cancers [51]. Berry bioactive phenolics impartanticancer effects through various complementary and over-lapping mechanisms of action including the induction ofmetabolizing enzymes; modulation of gene expression; andtheir effects on cell proliferation, apoptosis, and subcellularsignaling pathways. A large number of laboratory and animalstudies have shown that berries have anticancer properties [58].The anthocyanins present in blackberries and raspberries areimportant for the beneficial health effects associated withtheir antioxidant, anti-inflammatory, and chemopreventative

Fig. 2. Berry phenolics and flavonoids and their biological activities.

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properties; the biological activity of black raspberry againstesophageal, colon, and oral cancers has been demonstrated. Ithas long been established that cyanidin-3-glucoside and cyani-din-3-rutinoside are the respective major and minor anthocya-nins in blackberries [2,59]. In addition to anthocyanins, thesefruits are also a rich natural source of other chemopreventativephytochemicals such as flavonols, phenolic acids, ellagic acid,vitamins C and E, folic acid, and b-sitosterol. It is not uncommonfor fruits or any other plant material of related species todemonstrate varying degrees of biological activities ranging fromsome species being totally inactive to others exhibiting excep-tional activity [60].

Antimutagenic properties

Several chemical species from berry extracts have been iso-lated and found to possess antimutagenic activity, which blockcancer cell metabolism or kill cancer cells in culture, inactivatefree radicals and active oxygen species, exhibit antiestrogenicactivity, and inhibit mutagenesis. The most intensively studiedantimutagenic agents are the ellagitannins, especially ellagic acid[61,62]. The anticarcinogenic and anti-inflammatory effects offruits and berries have been well documented. Several plant

extracts inhibit the replication of cancer cells in culture, andmany plant compounds are highly effective in pure form, themost thoroughly studied of these being from black raspberriesand resveratrol [63,64]. The researchers reported that theextracts from raspberries, strawberries, and blueberries to inac-tivate mutagenesis by benzo[a] pyrene and cause suppression byblackberries for mutagenesis by 2-amino anthracene and foundthe magnitude of the effect to vary with the variety of berriesgrown in the same orchard under identical conditions [65,66].The inactivation of metabolically activated carcinogens iscaused by components of the berry extracts that inhibit thecytochrome P450 system responsible for converting carcinogeniccompounds into forms capable of covalent binding with DNA.Less understood is the ability of blackberry extracts to inhibitultraviolet-induced mutagenesis [67]. In addition to their effectson mutagenesis, raspberries, blackberries, and muscadine grapesalmost completely inhibit the activity of the matrix metal-loproteinases 2 and 9 involved in the invasion and metastasis ofcancer cells. Although antioxidants can clearly protect cells frommutagenesis at the initiation stage of carcinogenesis, their role inthe destruction of transformed cells is less clear [68]. Boivin andothers (2007) measured the antioxidant activity and anti-proliferative activities of berries and found red raspberries to be

Table 3Comparative 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 weightloss, 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, cyaniding-3-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 andpain 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 fatsfrom lymphatic system; and promotes cardiovascular health.

[103,104]

Bilberry� High in anthocyanins, flavonols.� High in vitamins C, E, and manganese.� Contains carotenoid, lutein, and

zeaxanthin.

Good for eyes, mouth, and gum health. Provides strength; powerfulanti-inflammatory; protects blood vessels and strengthens arteries;and improves circulation.

[17,45]

Raspberry� Rich in vitamins C, B, u-3, fibers, gallic

acid, ellagic acid, and acts as a strongantioxidant.

� Contains folate, iron, potassium,copper, and lutein.

Anticancer; prevents free radical damage; antimicrobial; and increasesmetabolic rate, which burns fats. Great for eye health and strength.

[17,45]

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; andstimulates 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; stimulatesdigestion, the liver, pancreas, spleen, and kidneys.

[75,107]

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among the most effective in blocking proliferation of differenttypes of cancer cells. However, they found no correlationbetween antioxidant activity and the ability to inhibit cancer cellreplication [60]. Likewise, Liu and others (2002) found nocorrelation between antioxidant activity and antiproliferativeactivity when comparing four different varieties of raspberries.In addition to its antioxidant effect, each extract also containsnumerous compounds that can affect cell survival and replica-tion by interacting with different replicative and metabolicpathways [69].

Antimicrobial properties

Certain berries rich in tannins have been found to increasebacterial infections. Two different types of polymeric tannins inthese berries protect against pathogenic bacteria. Presence of theA-type linkage of cranberry (Vaccinium macrocarpon) proantho-cyanidins may enhance both in vitro and urinary bacterial anti-adhesion activities [70]. Additionally, other tannin-containingberries may contribute to this effect, as berry juices of a mixtureof cranberries (Vaccinium oxycoccus) and lingonberries as well as

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cloudberry juice protect against urinary tract infection [71,72].Among the berries, cranberries, cloudberries, red raspberries,strawberries, and bilberries possess clear antimicrobial effectsagainst human pathogens. Berry ellagitannins are strong anti-microbial agents acting as possible anti-adherence compounds inpreventing the colonization and infection ofmany pathogens [34,35]. The phenolic extract of cloudberry, which is comprisedprimarily of ellagitannins, has the strongest antimicrobial effect,followed by red raspberry and strawberry. Salmonella spp.,Staphylococcus spp., Helicobacter spp., and Bacillus spp. are thebacteria that are most sensitive to berry phenolics. Additionally,the growth of Escherichia spp., Clostridium spp., and Campylo-bacter spp., but not the growth of Lactobacillus spp. and Listeriaspp., is inhibited by berry phenolics [41,73]. Red raspberryphenolics and its ellagitannin fraction also have powerful anti-microbial properties against the growth of human colonialpathogens, Klebsiella oxytoca and Proteus mirabilis [74]. Severalmechanisms of action in the inhibition of bacteria are involved,such as destabilization of cytoplasmic membrane, permeabiliza-tion of plasma membrane, inhibition of extracellular microbialenzymes, direct actions on microbial metabolism, and depriva-tion of the substrates required for microbial growth [34,35]. Theberry extracts inhibited the growth primarily of gram-negativebacteria but had no effect on gram-positive bacteria. However,there is very little information about the antimicrobial capacity ofphenolics present in berries, except in cranberry. Extracts of theaerial parts of bearberry and lingonberry were active against thegram-negative bacteria E. coli and P. vulgaris. The activity is knownto be due to the phenolic glycosides arbutin and metylarbutin.Cloudberry, raspberry, and strawberry extracts were the stron-gest inhibitors of gram-negative bacteria, especially Typhimurium[73,75]. Ellagic acid inhibits a range of pathogenic organismsincluding Vibrio cholerae, Shigella dysenteriae, and Campylobacterspp. It can be hypothesized that ellagitannins could be one ofthe components in cloudberries, raspberries, and strawberriescausing the inhibition against Salmonella. The antimicrobialeffects of berry extracts against gram-negative bacteria decreasedin 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 asblueberries that contain anthocyanins, the flavonoid pigmentresponsible for their red to bluish hue. Anthocyanins exhibitantioxidant activity and inhibit oxidation of LDL. They also havevasoprotective and anti-inflammatory activity. Anthocyanin-richextracts from European berries such as the bilberry (Vacciniummyrtillus) have been sold commercially to treat microcirculationdisease and to maintain normal vascular permeability [77].Extensive pharmacologic and clinical studies have demonstratedthat flavonoids are the active substances that are largelyresponsible for the action of the drug. The main pharmacologicactivities of berries are primarily cardiovascular ones, includingcardiotonic, antiarrithythmic, hypotensive, and hypolipidemiceffects [78]. Raspberry phytochemicals beneficially modulateenzyme activity, cellular pathways, and gene expression. Inaddition to reducing oxidized-LDL formationvia their antioxidantactivity, raspberry phytochemicals have demonstrated anti-atherosclerotic and anti-inflammatory activities, which mayprovide protection against cardiovascular diseases [79]. Manystudies have demonstrated the ability of raspberry phytochemi-cals to reduce cancer cell growth in vitro. Anthocyanins have the

ability to down-regulate cyclooxygenase-2 expression andenzyme activity, a mechanism for its antiproliferative actions onmany different human cancer cell lines [31,80]. In contrast, ellagicacid’s mechanism for its antiproliferative actions across manydifferent human cancer cell lines is via induction of apoptosis.Despite the antiproliferative activities of both anthocyanin andellagic acid, it is the ellagitannin fractions that mostly account forthis biological effect by red raspberryextracts. In vitro studies alsohave found phytochemicals from black raspberry extracts to beeffective in reducing vascular endothelial growth factor expres-sion, a promoter of angiogenesis, which is a critical step for tumormetastasis [81,82].

Neuroprotective properties

Foods and food ingredients, in particular components chem-ically classified as antioxidants, have been reported to exerta beneficial effect in neurodegeneration. In the developed world,life expectancy is increasing, with a concomitant increasedincidence of many age-related diseases, such as cancer, cardio-vascular troubles, and neurodegeneration [83,84]. Substantialevidence supports the hypothesis that oxidative stress playsa major role in the pathogenesis of neurodegenerative disease.Oxidative stress is generally caused by the excessive accumula-tion of ROS in cells and has been implicated in the developmentof many neurodegenerative diseases, including Parkinson’sdisease, Huntington’s disease, amyotrophic lateral sclerosis, andAlzheimer’s disease [85,86]. Behavioral studies in rodents haverevealed an attenuation of brain aging when strawberries,blueberries, or blackberries are ingested. Evidence is increasingthat these phytochemicals, and by association the foods, havebeneficial effects on human health and reduce the risk ofcardiovascular disease and type 2 diabetes [87,88].

Conclusion

This review demonstrates that a number of in vitro andin vivo studies, using cell cultures of animal and human cells,have suggested that bioactive compounds of berries positivelyshow an effect on human health. The presented characteristics ofvarious berry fruits point to vast differences in the type of theirbioactive compounds; such differences are observed with regardto both the content and the qualitative composition of thosecompounds. The most significant health benefits are ascribed tophenolic compounds and vitamin C, which result mostly fromantioxidant, anticancer, antimutagenic, antimicrobial, anti-inflammatory, and neuroprotective properties. The use of allthese biological activities presented in this review related toberry bioactive phenolics and flavonoids might promote thedevelopment of alternative berry compounds for the preventionand control of various diseases and disorders. This issue will becritical for future research priorities that may offer numerousopportunities for berries to be used in the food industry andmedicine and will provide a wide range of health benefits.Further research is needed on this subject regarding the issuesrelated to plant breeding and genetic approaches at the interfacewith the synthesis of compounds for nutrition and healthpurposes should receive more emphasis and attention.

Acknowledgments

This work was supported by a grant from Bio-Green 21Program (No. PJ009074), Rural Development Administration,Republic of Korea.

S. H. Nile, S. W. Park / Nutrition 30 (2014) 134–144 143

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