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Critical Reviews in Food Science and Nutrition
ISSN: 1040-8398 (Print) 1549-7852 (Online) Journal homepage: http://www.tandfonline.com/loi/bfsn20
Anti-inflammatory effects of phytochemicals fromfruits, vegetables, and food legumes: A review
Fengmei Zhu, Bin Du & Baojun Xu
To cite this article: Fengmei Zhu, Bin Du & Baojun Xu (2018) Anti-inflammatory effects ofphytochemicals from fruits, vegetables, and food legumes: A review, Critical Reviews in FoodScience and Nutrition, 58:8, 1260-1270, DOI: 10.1080/10408398.2016.1251390
To link to this article: https://doi.org/10.1080/10408398.2016.1251390
Published online: 12 Jun 2017.
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Anti-inflammatory effects of phytochemicals from fruits, vegetables, and foodlegumes: A review
Fengmei Zhua, Bin Dua,b, and Baojun Xub
aHebei Normal University of Science and Technology, Qinhuangdao, Hebei, China; bFood Science and Technology Program, Beijing NormalUniversity—Hong Kong Baptist University United International College, Zhuhai, Guangdong, China
ABSTRACTInflammation is the first biological response of the immune system to infection, injury or irritation.Evidence suggests that the anti-inflammatory effect is mediated through the regulation of variousinflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-a, interferongamma-g as well as noncytokine mediator, prostaglandin E2. Fruits, vegetables, and food legumes containhigh levels of phytochemicals that show anti-inflammatory effect, but their mechanisms of actions havenot been completely identified. The aim of this paper was to summarize the recent investigations andfindings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables,and food legumes. Specific cytokines released for specific type of physiological event might shed somelight on the specific use of each source of phytochemicals that can benefit to counter the inflammatoryresponse. As natural modulators of proinflammatory gene expressions, phytochemical from fruits,vegetables, and food legumes could be incorporated into novel bioactive anti-inflammatory formulationsof various nutraceuticals and pharmaceuticals. Finally, these phytochemicals are discussed as the naturalpromotion strategy for the improvement of human health status. The phenolics and triterpenoids in fruitsand vegetables showed higher anti-inflammatory activity than other compounds. In food legumes, lectinsand peptides had anti-inflammatory activity in most cases. However, there are lack of human study dataon the anti-inflammatory activity of phytochemicals from fruits, vegetables, and food legumes.
KEYWORDSFruits and vegetables; foodlegumes; anti-inflammatoryproperty; phytochemicals;animal model
Introduction
Inflammation is a biological process in response to infec-tion, injury or irritation (Wang et al., 2013). Chronicinflammation seems to be associated with different types ofdiseases, such as arthritis, allergy, atherosclerosis, and evencancer (Devi et al., 2015). The process of inflammation is acomplicated immune response that can be defined as thesequential release of pro-inflammatory cytokines (Lin andTang, 2008). Therefore, inhibition of the overproduction ofinflammatory mediators, especially pro-inflammatory cyto-kines, such as interleukin (IL)-1b, IL-6, and tumor necrosisfactor alpha (TNF-a), may prevent or suppress a variety ofinflammatory diseases (Kim et al., 2003). Since ancienttimes, inflammatory conditions and their related disordershave been treated with plants or plant-derived formulations.Furthermore, numerous natural products rich in antioxi-dants display protective effects against inflammation. Theanti-inflammatory activities of several plant extracts andisolated compounds have already been scientifically demon-strated (Mueller et al., 2010). The anti-inflammatory prop-erties of naturally occurring phytochemicals are attributedto the decrease in certain cancers in both in vitro and invivo studies (Kang et al., 2005).
Nitric oxide (NO) is one of the major inflammatory media-tors. The phytochemicals that reduce NO production by induc-ible NOS (iNOS) without affecting endothelial NOS orneuronal NOS may be beneficial for the development of anti-inflammatory agents (Kim et al., 2004). Therefore, inhibition ofiNOS activity or down-regulation of iNOS expression is desir-able to reduce the extent of inflammatory response. In additionto iNOS, cyclooxygenase-2 (COX-2) is involved with variousinflammatory processes and is highly expressed in cell typesrelated to inflammatory processes including macrophages andmast cells, when stimulated with pro-inflammatory cytokinesand bacterial lipopolysaccharide (LPS) (Needleman andIsakson, 1997). However, TNF-a and IL-1b are also prominentcontributors to chronic inflammatory diseases (Mcinnes andGeorg, 2011). Phytochemicals mediate inflammation via kin-ases such as protein kinase C and mitogen-activated proteinkinase. Phytochemicals inhibit these aforementioned enzymesby altering the DNA-binding capacities of transcription factorssuch as nuclear factor kappa-B (NF-kB). Consequently, theexpression rate of the target gene is controlled. NF-kB is amajor effector pathway involved in inflammation (Garc�ıa-Lafuente et al., 2009). Another anti-inflammatory effect of
CONTACT Baojun Xu baojunxu@uic.edu.hk Food Science and Technology Program, Beijing Normal University—Hong Kong Baptist University UnitedInternational College, Zhuhai, Guangdong 519085, China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/bfsn.Authors Fengmei Zhu and Bin Du contributed equally to this work.© 2018 Taylor & Francis Group, LLC
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION2018, VOL. 58, NO. 8, 1260–1270https://doi.org/10.1080/10408398.2016.1251390
phytochemicals during the allergic reaction is inhibition of therelease of histamine (Rathee et al., 2009).
We recently reviewed the anti-inflammatory effects of fungalbeta-glucans (Du et al., 2015). A wide array of phytochemicals,particularly those present in edible and medicinal plants, havebeen reported to possess substantial anti-inflammatory activi-ties. However, the exact mechanisms of action of phytochemi-cals need to be ascertained for majority of the fruits, vegetables,and food legumes. Herein, this review commences with therecent insights gained on the in vitro and in vivo studies onanti-inflammatory activities of phytochemicals from fruits, veg-etables, and food legumes (Table 1 and Figure 1). The generalanti-inflammation response pathways of phytochemicals arelisted in Figure 2. However, the phytochemicals from differentfruits, vegetables, and food legumes may dramatically differbased upon their species, investigation methods, and the mediaof extraction, the anti-inflammation response pathways of dif-ferent food may differ in certain circumstances. The detailedmechanisms in terms of anti-inflammatory effects of individualcompound or food were presented in the following text.Figure 3 presented the typical chemical structures of commoncompounds from fruits, vegetable, and food legumes thatexhibited anti-inflammation effects.
Anti-inflamatory properties of fruits and vegetables
Crude extracts
Cytokine secretion regulatory activities using ethanolic extractsof strawberry and mulberry fruit juice were assessed in murineprimary splenocytes and peritoneal macrophages (Liu and Lin,2013). Strawberry and mulberry extracts with pine bark extract(0.5 g L¡1) significantly decreased (IFN-g C IL-2 C IL-12)/IL-10 (Th1/Th2) cytokine secretion ratios of splenocytes in theabsence or presence of LPS and TNF-a/IL-10 (pro-/anti-inflammatory) cytokine secretion ratios in the presence of LPSin dose-dependent manners. Frontela-Saseta et al. (2013) intheir experiment with co-culture system showed cell barrierdysfunction and over-production of IL-8, NO and reactive oxy-gen species (ROS). In the inflamed cells, incubation with nondi-gested samples reduced (p < 0.05) the production of IL-8 andNO compared with the digested samples. ROS productionincreased in the inflamed cells exposed to the digested commer-cial red fruit juice (86.8 § 1.3%) compared with fresh juice(77.4 § 0.8%).
According to Etoh et al. (2013), citrus peel extract decreasedthe release of TNF-a and NO from RAW264.7 cells stimulatedby LPS in a dose-dependent manner. In addition, citrus peelextract suppressed the expression of iNOS and nuclear translo-cation of NF-kB in RAW 264.7 cells. Fazio et al. (2013) evalu-ated Sambucus and Rubus spp. seeds extracts for theirinhibitory effects on the production of LPS-induced inflamma-tory mediators (NO, CCL-20) in RAW 264.7 cells. Blackberryextract decreased NO release in a concentration-dependentway with almost 60% inhibition at the highest dose (50 mg/mL). The results showed that the methanolic extracts fromRubus seeds have strong anti-inflammatory properties.
Li et al. (2012) investigated the anti-inflammatory effects ofthe fractions of Chinese pear fractionated with petroleum ether,
ethyl acetate, and n-butanol, respectively. In the carrageenan-induced rat paw edema test, the ethyl acetate fraction showedthe strongest inhibition of edema formation 0.5–5 h afterinduction of edema, followed by n-butanol fraction. Ethyl ace-tate fraction also displayed potent anti-inflammatory activityagainst xylene-induced ear edema (22.0% and 43.7%, respec-tively) and acetic acid-induced extravasation of Evan’s blue dye(39.58% and 49.92%, respectively) at a dose of 200 and 400 mg/kg, respectively. In another study, Hsu et al. (2012) evaluatedthe inhibitory effect of wild bitter melons on Propionibacteriumacnes-induced inflammation. The results showed that ethyl ace-tate extract of wild bitter melons in vitro potently suppressedpro-inflammatory cytokine and matrix metalloproteinase-9 lev-els in P. acnes-stimulated THP-1 human monocytic cells.
Phenolics
Epidemiological evidence shows that supplementations withfruits and vegetables rich in polyphenols are beneficial in bothforestalling and reversing the deleterious effects of aging onneuronal communication and behavior. For example, phyto-chemicals, especially phenolics in fruits and vegetables, are themajor bioactive components known to show various healthbenefits (Pereira and Maraschin, 2015; Chen et al., 2016; Xiao,2016; Xiao et al., 2016). The observed health benefits are due tothe antioxidant and anti-inflammatory properties of the poly-phenolic compounds found in these fruits and vegetables(Rice-Evans and Miller, 1996). Lau et al. (2007) found the pre-ventive effect of blueberry polyphenols against inflammation-induced activation of microglia. Their results indicate thattreatments with phenolic extract of blueberry inhibited the pro-duction of NO as well as IL-1b and TNF-a in cell-conditionedmedia from LPS-activated BV2 microglia. Furthermore, mRNAand protein levels of iNOS and COX-2 in LPS-activated BV2cells were significantly reduced by treatments with blueberryphenolic extract. In another study, the inhibitory effects of phe-nolic compounds in ginger on NO and prostaglandin E2(PGE2) production in LPS-induced RAW 264.7 macrophageswere measured (Chien et al., 2008). Zerumbone and 3-O-methyl kaempferol demonstrated potent inhibition on nitricoxide (NO) production, and also significantly suppressed iNOSexpression in a dose-dependent manner. However, zerumbonehad greater anti-inflammatory effects than 3-O-methyl kaemp-ferol. Comalada et al. (2006) elucidated that quercetin andluteolin inhibited the production of TNF-a and NO, and sup-pressed iNOS expression in LPS-activated macrophages, aneffect that has been associated with the inhibition of the NF-kBpathway. Furthermore, Garc�ıa-Mediavilla et al. (2007) sug-gested that kaempferol significantly decreased iNOS, COX-2,and reactive C-protein (CRP) in a concentration-dependentmanner at all concentration levels. The study suggests that themodulation of iNOS, COX-2, and CRP by kaempferol maycontribute to the anti-inflammatory effects of these two struc-turally similar flavonoids in Chang Liver cells, via mechanismslikely to involve blockade of NF-kB activation and the resultantup-regulation of the pro-inflammatory genes. In another study,the effect of naringenin was characterized using LPS-stimulatedmacrophages (Bodet et al., 2008). The results indicate that nar-ingenin is a potent inhibitor of the pro-inflammatory cytokine
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1261
Table1.
Summaryoftheanti-inflam
matoryeffectsofph
ytochemicalsfrom
fruits,vegetables,andfood
legu
mes.
Classesof
Phytochemicals
Components
DietarySources
Mechanism
ofActio
nsExperim
entalM
odel
References
Crud
eextracts
Procyanind
inextract
Grape
seeds
Inhibitthe
overproductio
nofNOandPG
E 2RA
W264.7macroph
ages
model
(Terraet
al.,2007)
Fruitjuice
ethanolextracts
Strawberryandmulberry
Decreasesplenocytes’(IFN-g
CIL-2C
IL-12)/IL-10(Th1/Th2)cytokine
secretionratio
sMurineprimarysplenocytesand
peritonealm
acroph
ages
model
(LiuandLin,2013)
Fruitjuice
with
pine
barkextract
Pine
bark
Redu
ce(p
<0.05)the
productio
nofIL-8andNO
Caco-2cells
andRA
W264.7
macroph
ages
asmodel
(Frontela-Sasetaetal.,
2013)
Citrus
peelextract
Citrus
Decreasethereleaseof
TNF-aandNO
RAW264.7cells
model
(Etohetal.,2013)
SambucusandRubusspeciesseedsextracts
SambucusandRubus
species
Inhibitoryeffectson
theproductio
nof
NOandCC
L-20
RAW
264.7cells
model
(Garc� ıa-Lafuenteet
al.,
2009)
Ethylacetateextract
Chinesepear
Inhibitio
nofedem
aform
ation0.5–5hafteredemaindu
ction
Carrageenan-indu
cedratp
awedem
amodel
(Lietal.,2012)
Ethylacetateextract
Wild
bittermelons
Supp
resspro-inflam
matorycytokine
andmatrix
metalloproteinase-9
levels
THP-1cells
model
(Hsu
etal.,2012)
Aqueousextract
Mun
gbean
Potent
inflam
matorymediator(NO)inhibito
rs;reduceearedemain
mice
Invitroandinvivo
modelS
(Aliet
al.,2014)
Acetone-waterextracts
Mun
gbean
Sign
ificant
anti-inflam
matoryeffects
RAW
264.7macroph
ages
model
(Zhang
etal.,2013)
Extracts
Mun
gbean
AttenuateLPS-indu
cedreleaseof
severalchemokines
RAW
264.7macroph
ages
model
(Zhu
etal.,2012b)
Acetoneextract
Blackbean
Strong
COX-1andCO
X-2inhibitoryeffects
Invitromodel
(Oom
ahet
al.,2010)
Ethanolextract
Adzukibean
Supp
ressthereleaseof
PGE 2
andNO;dow
n-regu
latedLPS-indu
ced
mRN
Aexpression
ofiNOSandCO
X-2.
RAW
264.7macroph
ages
model
(Yuet
al.,2011)
Crud
emethanolic
extracts
Legu
mes
InhibitP
GE 2
Invitromodel
(Zia-Ul-H
aqetal.,
2013)
Phenolicrichextracts
Whitekidn
eybeansand
roun
dpu
rplebeans
Redu
ctionofNOproductio
nandcytokine
mRN
Aexpression
RAW
264.7macroph
ages
model
(Garc� ıa-Lafuenteet
al.,
2014)
Ethanolextract
Redbean
InhibitN
Oproductio
nInvitroandinvivo
models
(Parketal.,2011)
Phenolics
Polyph
enols
Blueberry
Inhibitthe
productio
nof
NO,IL-1b
andTN
F-a
LPS-activated
BV2microgliamodel
(Lau
etal.,2007)
Zerumbone
and3-O-m
ethylkaempferol
Ginger
InhibitN
OandPG
E 2productio
n,iNOSexpression
RAW
264.7macroph
ages
model
(Chien
etal.,2008)
Quercetinandluteolin
—InhibitTNF-aproductio
nas
wellasiNOSexpression
andNOproductio
nRA
W264.7macroph
ages
model
(Com
aladaet
al.,2006)
Kaem
pferol
—Decreaseof
iNOS,CO
X-2andreactiveCR
Plevel
Livercellsmodel
(Garc� ıa-Mediavilla
etal.,2007)
Naringenin
—Apotent
inhibitoro
fthe
pro-inflam
matorycytokine
RAW
264.7macroph
ages
model
(Bodetet
al.,2008)
Punicalagin,pu
nicalin,strictin
inAand
granatinB
Pomegranate
redu
ceproductio
nofNOandPG
E 2RA
W264.7macroph
ages
model
(Lee
etal.,2008;
Romieretal.,2008)
Granatin
BPomegranate
Astrong
inhibitoryeffectagainstinflam
mationstimulators
Carrageenan-indu
cedpawedem
amodel
(Lee
etal.,2010)
Nariru
tinCitrus
Inhibitthe
releaseofNO,PGE 2,IL-1b
andTN
F-a
RAW
264.7macroph
ages
model
(Haet
al.,2012)
Flavonevelutin
Acaifruit
Show
excellent
anti-inflam
matorycapacity
RAW
264.7macroph
ages
model
(Kanget
al.,2011)
Anthocyanin
Blacksoybean
Haveanti-inflam
matoryactivity
forp
enile
plaque
form
ation
RatP
eyroniediseasemodels
(Sohnetal.,2014)
Phenoliccompounds
Navyandblackbean
Redu
cemRN
Aexpression
ofcolonicinflam
matorycytokines(IL-6,IL-9,
IFN-g
andIL-17A
)and
increase
anti-inflam
matoryIL-10
Amouse
modelof
acutecolitis
(Zhang
etal.,2014)
Triterpenoids
monom
ericcompounds
Pear
Indicatestrong
eranti-inflam
matoryactivities
RAW
264.7macroph
ages
model
(Lietal.,2014)
Pentacyclic
triterpenoids
Apple
Implicateintheanti-inflam
matoryproperties
T84coloncarcinom
acells
model
(Muelleretal.,2013)
Saponins
Soybeansaponins
Soybean
Inhibitthe
releaseofPG
E 2,N
O,TNF-aandMCP-1
RAW
264.7macroph
ages
model
(Kanget
al.,2005)
Soyasaponins
Soybean
Supp
resstheiNOSenzymeactivity
anddown-regu
latedtheiNOSmRN
Aexpression
RAW
264.7macroph
ages
model
(Zha
etal.,2011)
Soyasaponins
Soybean
Redu
ceinflam
matorymarkers,colon
leng
th,m
yeloperoxidase,lipid
peroxide,proinflam
matorycytokinesandNF-kBactivationinthe
colon
TNBS-indu
cedcoliticmicemodel
(Lee
etal.,2010)
Angu
larin
A,angu
lasaponins
A-C,and
azukisaponinsIIIandVI
Adzukibean
InhibitN
Oproductio
nRA
W264.7macroph
ages
model
(Jiang
etal.,2014)
Lectins
Lectins
Butterflypea
Anti-inflam
matoryactivity
Thepawedem
aindu
cedby
carrageenanmodel
(Leite
etal.,2012)
1262 F. ZHU ET AL.
Monocot
lectin
Cannalim
bata
seeds
Redu
ctionofinflam
mation
Form
alinmodel
(Ara� ujoetal.,2013)
Lectin
Canavalia
boliviana
Inhibitthe
pawoedemaindu
cedby
carrageenan
Invivo
model
(Bezerraet
al.,2014)
Soybeanagglutinin
Soybean
Inhibitoryeffecton
neutroph
ilmigratio
nInvitromodel
(Benjaminetal.,1997)
Polysaccharid
esPolysaccharid
eWelsh
onion
reactivenitrogen
speciesredu
ction;theincrease
intheactivities
ofantio
xidant
enzyme
Micemodel
(Wangetal.,2013)
Water-solub
lepolysaccharid
eChaenomeles
speciosa
fruit
Redu
cedthegene
indu
ctionofTN
F-a,IFN
-gandgranulocytecolony-
stimulatingfactor
RAW
264.7macroph
ages
model
(Zhu
etal.,2012a)
Peptides
Bioactivepeptides
Soybean
Inhibitio
non
inflam
matorymarkerssuch
asNO,iNOS,PG
E 2,COX-2and
TNF-a
RAW
264.7macroph
ages
model
(Vernaza
etal.,2012)
Lunasin
Soybean
Redu
cetheproductio
nofRO
S;inhibitthe
releaseof
pro-inflam
matory
cytokines(TNF-a)and
IL-6
RAW
264.7macroph
ages
model
(Hern� and
ez-Ledesma
etal.,2009)
Other
compounds
Monogalactosyldiacylglycerol
Citrus
hystrix
Exhibith
igheranti-inflam
matoryactivity
TPA-indu
cededem
aearsmice
model
(Murakam
ietal.,1995)
Monogalactosyldiacylglycerol
Vegetables
Dow
nstreaminflam
matorymediators,COX-2,iNOS,NOandPG
E 2RA
W264.7macroph
ages
model
(Hou
etal.,2007)
Phenethylisothiocyanate
Cruciferous
vegetables
Sppression
ofTRIF-dependent
pathwaysof
TLR3
andTLR4
RAW
264.7macroph
ages
model
(Parketal.,2013)
Indole-3-carbinol
Broccoli,cabb
age,
cauliflow
er,brussels
sprouts.
Attenuatetheproductio
nofpro-inflam
matorymediatorssuch
asNO,IL-
6,andIL-1b
RAW264.7cells
andTH
P-1cells
models
(Jiang
etal.,2013)
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1263
response induced by LPS in both macrophages and in wholeblood.
Pomegranate peels are characterized with substantialamounts of phenolic compounds, including flavonoids (antho-cyanins, catechins, and other complex flavonoids) and hydro-lyzable tannins (punicalin, pedunculagin, punicalagin, gallicacid, and ellagic acid) (Ismail et al., 2012). The anti-inflamma-tory components of pomegranate peel, that is, punicalagin,
punicalin, strictinin A, and granatin B significantly reduced theproduction of NO and PGE2 by inhibiting the expression ofpro-inflammatory cytokines (Lee et al., 2008; Romier et al.,2008). In case of animal models, Ouachrif et al. (2012) investi-gated anti-inflammatory properties of the pomegranate peelfollowing intraperitoneal (25, 50, and 100 mg/kg) and intra-cerebroventricular (10, 25, and 50 mg/3 mL/rat) administrationin rats. The results indicated pain index reduction of 52–82%
Figure 1. Causal relationship of inflammation and anti-inflammation.
Figure 2. The pathway of anti-inflammatory effect of phytochemicals.
1264 F. ZHU ET AL.
and a significant reduction in egg albumin-induced hind pawinflammation at the same levels of dosage as intra-peritonealtest. Moreover, Lee et al. (2010) evaluated a strong inhibitoryeffect against inflammatory stimulators during carrageenan-
induced paw edema in mice following oral administration ofgranatin B (2.5 and 10 mg/kg). Significant inhibitory effectswere observed after 6 h of pomegranate peel active componentadministration when compared to indomethacin. As a result ofthese properties, pomegranate peel extract and hydrolyzabletannins, in the form of standardized active components, are avery effective treatment strategy against inflammatory disor-ders. In one study, narirutin fraction from citrus peels inhibitedthe release of NO and PGE2 through suppressing the expres-sion of iNOS and COX-2, respectively in LPS-stimulated mac-rophages. The release of IL-1b and TNF-a was also reduced bynarirutin fraction in a dose-dependent manner (Ha et al.,2012). Thus, narirutin fraction has the potential to be used as afunctional dietary supplement and as an effective anti-inflam-matory agent. The presence of polyphenolic components inacai (one of the Amazon’s most popular fruits) is linked mainlyto the antioxidant, anti-inflammatory, anti-proliferative, andcardioprotective activities (Yamaguchi et al., 2015). Kang et al.(2011) isolated five compounds from acai pulps. The flavones,velutin, from acai pulps showed excellent anti-inflammatorycapacity in mouse macrophages, indicating a potential athero-protective effect. Moreover, Terra et al. (2007) evaluated theanti-inflammatory effect of procyanindin extract from grapeseeds in RAW 264.7 macrophages stimulated with LPS plusIFN-g. The results showed that procyanindin extract fromgrape seeds caused a rapid enhanced production of PGE2 andNO. The results demonstrated that procyanindin extract signif-icantly inhibited the over production of NO in both dose andtime dependent manners. Procyanindin extract caused amarked inhibition of PGE2 synthesis when administered duringactivation.
Polysaccharides
Wang et al. (2013) investigated the anti-inflammatory effects ofan aqueous extract (mainly polysaccharide) of Welsh oniongreen leaves with mice model. According to them, the anti-inflammatory and analgesic effects of Welsh onion green leavesmay be related to the decrease in reactive nitrogen species andassociated with the increase in antioxidant enzymes (catalase,superoxide dismutase (SOD), and glutathione peroxidase).Another study reported that water-soluble polysaccharide fromfruits of Chaenomeles speciosa suppressed the gene induction ofTNF-a, IFN-g, and granulocyte colony-stimulating factor inLPS-induced RAW 264.7 cells (Zhu et al., 2012a).
Triterpenoids
Li et al. (2014) compared the contents of total triterpenesbetween peel and flesh of 10 different pear cultivars. The anti-inflammatory activities of monomeric compounds were alsomeasured. All the chemical components found in the pear peelwere approximately 6–20 times higher than those in the fleshof pear. Peel and flesh from Yaguang, Hongpi, Qingpi, and Gui-fei varieties contained relatively more total triterpenes and indi-cated stronger anti-inflammatory activities. In another study,Mueller et al. (2013) studied pentacyclic triterpenoids in applepeel for detecting in vitro anti-inflammatory effects using T84colon carcinoma cells. Their results showed that triterpenoids
Figure 3. The typical chemical structures of anti-inflammatory phytochemicals infruits, vegetables, and food legumes.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1265
present in apple peel could be implicated in the anti-inflamma-tory properties of apple constituents, suggesting that these sub-stances might be helpful in the treatment of inflammatorybowel disease (IBD) when given as nutrient supplements.
Other compounds
Galactolipids are a class of compounds widely found in theplant kingdom, including edible plants, and are importantcomponents of their cell membranes. Several galactolipids havebeen shown to possess in vitro and/or in vivo anti-inflamma-tory activity (Christensen, 2009). In one study, monogalactosyl-diacylglycerol, which is a predominant membrane lipid in seedplants and the most abundant polar lipid, exhibited potentanti-inflammatory activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema formation on mouse ears(Murakami et al., 1995). Hou et al. (2007) found that monoga-lactosyldiacylglycerol had chemopreventive effects by suppress-ing cytoplasmic NF-kB and downstream inflammatorymediators, COX-2, iNOS, NO, and PGE2. Moreover, phenethylisothiocyanate (PEITC) found in cruciferous vegetables showeda positive effect on chronic inflammatory diseases, which aremediated through modulation of Toll/IL-1 receptor domain-containing adapter-inducing interferon-b (TRIF)-dependentsignaling pathway of Toll-like receptors (TLR) (Park et al.,2013). The suppression of TRIF-dependent pathways of TLR3and TLR4 by PEITC is accompanied by the down-regulation ofthe NF-kB activation and interferon regulatory factor 3, andthe expression of their target genes, including IFN-b and IFNinducible protein-10. Similarly, Jiang et al. (2013) assessed invitro and in vivo anti-inflammatory effects of indole-3-carbinoland its molecular mechanisms. Indole-3-carbinol attenuatedthe production of pro-inflammatory mediators such as NO, IL-6, and IL-1b in LPS-induced RAW 264.7 cells and THP-1 cellsthrough the attenuation of TRIF-dependent signaling pathway.
Anti-inflammatory properties of food legumes
A large range of species of food legumes are cultivated and con-sumed throughout the world (Patto et al., 2014). In recentyears, colored common beans, including pinto beans and blackbeans, have attracted a great deal of attention because of theirfunctional pigments and health-promoting effects in relation toprevention of chronic diseases, including cancers, cardiovascu-lar diseases, obesity, and diabetes (Xu and Chang, 2009). Phe-nolic compounds, such as phenolic acids, flavonols, flavones,isoflavones, anthocyanins, and condensed tannins, have beenidentified and characterized in food legumes (Xu and Chang,2011; Djordjevic, 2011; Sreerama et al., 2012; Das and Parida,2014).
Crude extracts
Ali et al. (2014) evaluated the anti-inflammatory and antinoci-ceptive activities of untreated mung bean, germinated mungbean, and fermented mung bean on both in vitro and in vivostudies. The results indicated that both germinated andfermented mung bean aqueous extract exhibited potent anti-inflammatory and anti-nociceptive activities in a dose-
dependent manner. In vitro results showed that both germi-nated and fermented mung bean were potent inhibitors ofinflammatory mediator (NO) at both 2.5 and 5 mg/mL. Furtherin vivo studies showed that both germinated and fermentedmung bean aqueous extract at 1000 mg/kg can significantlyreduce ear edema in mice caused by arachidonic acid. More-over, Oomah et al. (2010) reported that acetone extract of blackbean hull exhibited strong COX-1 (IC50 D 1.2 mg/mL) andCOX-2 (IC50 D 38 mg/mL) inhibitory effects, even outperform-ing than aspirin. Bean hull water extracts were stronger inhibi-tors of 15-lipoxygenase (15-LOX), than corresponding acetoneextracts. In another study, Yu et al. (2011) suggested thatadzuki bean (Phaseolus angularis) ethanol extract dose-depen-dently suppressed the release of PGE2 and NO in macrophagesand strongly down-regulated LPS-induced mRNA expressionof iNOS and COX-2. The results showed that adzuki bean etha-nol extract can be further developed as a promising anti-inflammatory remedy because it targets multiple inflammatoryenzymes and transcription factors. Zhang et al. (2013) foundthat mung bean acetone-water extracts possessed significantanti-inflammatory effects in LPS-stimulated RAW264.7 mousemacrophage cells at 100 mg/mL concentration.
Furthermore, Zia-Ul-Haq et al. (2013) investigated crudemethanolic extracts of black gram, green gram, soybean, andlentil for anti-inflammatory activity by COX-2 producing PGE2inhibitory assay. They observed 73.9%, 79.8%, 92.2%, and74.5% inhibition for black gram, green gram, soybean, and len-til, respectively, at 20 mg/mL extract concentration.Garc�ıa-Lafuente et al. (2014) determined the anti-inflammatoryactivities of phenol rich extracts obtained from white kidneybeans and round purple beans. Round purple bean extractsindicated a higher anti-inflammatory activity by decreasing theproduction of NO and expression of cytokine mRNA of LPS-stimulated macrophages. In another study, mung bean extractsdose-dependently attenuated LPS-induced release of severalchemokines in macrophage cultures. Oral administration ofmung bean extracts significantly increased animal survival ratesfrom 29.4% to 70% (Zhu et al., 2012b).
Park et al. (2011) used in vitro and in vivo experimentalmodels to investigate the anti-inflammatory potential of thebutanol fraction of red bean ethanol extract. Treatment withbutanol fraction of red bean ethanol extract inhibited NO pro-duction in LPS-stimulated macrophages through suppressionof extracellular signal regulated kinase and inhibitory kappa Balpha (IkBa) activation. The result suggested the possible use-fulness of red beans in the treatment of inflammatory diseases.
Saponins
Soyasaponins are found in soybeans and other legumes (Guanget al., 2014). Saponins have received much attention in relationto the health effects of food legumes. Kang et al. (2005)investigated the effects of soybean saponins on the productionof pro-inflammatory mediators in LPS-stimulated peritonealmacrophages. Soybean saponins significantly inhibited therelease of PGE2, NO, TNF-a, and monocyte chemotactic pro-tein-1 (MCP-1) in a dose-dependent manner. Soybean sapo-nins also down-regulated the expression of COX-2 and iNOSat mRNA/protein levels. Moreover, soybean saponins
1266 F. ZHU ET AL.
suppressed NF-kB activation by blocking IkBa degradation.Successful in vitro assays indicated that soybean saponinsexhibit anti-inflammatory properties by suppressing the tran-scription of inflammatory cytokine genes through the NF-kBsignaling pathway. In addition, Zha et al. (2011) investigatedthe inhibitory effects of soyasaponins (25–200 mg/mL) on theinduction of NO and iNOS in murine RAW 264.7 cells acti-vated with LPS. The soyasaponins suppressed both the iNOSenzyme activity and down-regulated the iNOS mRNA expres-sion in a dose-dependent manner. The findings showed thatsoyasaponin exhibited anti-inflammatory properties by sup-pressing NO production in LPS-stimulated RAW264.7 cellsthrough attenuation of NF-kB-mediated iNOS expression. In astudy based on animal model, Lee et al. (2010) investigated theinhibitory effects on inflammatory markers in 3,4,5-trinitro-benzenosulfonic acid (TNBS)-induced colitic mice. Oraladministration of soyasaponin (10 and 20 mg/kg) to TNBS-treated colitic mice significantly reduced inflammatorymarkers, colon length, myeloperoxidase, lipid peroxide, proin-flammatory cytokines, and NF-kB activation in the colon, aswell as increased glutathione content, SOD, and catalase activ-ity. Moreover, Jiang et al. (2014) reported that angularin A,angulasaponins A-C, and adzukisaponins III and VI fromadzuki bean (Vigna angularis) presented inhibitory effects onNO production in LPS-activated RAW264.7 macrophages,with IC50 values ranging from 13 to 24 mM.
Peptides
Legumes are an important source of proteins from food. Bio-logical activities of proteins and peptides from legume seedshave been observed (Duranti, 2006). Vernaza et al. (2006)investigated that soybean flours with bioactive peptides showeda significant (p < 0.05) inhibition on inflammatory markerssuch as NO (20.5–69.3%), iNOS (22.8–93.6%), PGE2 (64.0–88.3%), COX-2 (36.2–76.7%), and TNF-a (93.9–99.5%) inLPS-induced RAW 264.7 macrophages. Moreover, Hern�andez-Ledesma et al. (2009) found peptide lunasin reduced the pro-duction of ROS in LPS-induced RAW 264.7 macrophages in asignificant dose-dependent manner. Lunasin also inhibited therelease of pro-inflammatory cytokines (TNF-a) and IL-6.
Phenolics
Dry beans are typically processed and the seed coats may beremoved and discarded prior to consumption. Therefore, a bet-ter understanding of the anti-inflammatory activity of coloreddry bean seed coats would be beneficial in determining theirpotential use as an ingredient in the functional food and nutra-ceutical industry (Pitura, 2011). Legume seed hulls are richsources of polyphenolics and natural antioxidants (Moise et al.,2005; Luo, Cai, Wu, Xu, 2016). Boudjou et al. (2013) found thataqueous ethanolic (80%) extract of lentil hulls had high anti-inflammatory activities preferentially inhibiting 15-LOX (IC50
D 55 mg/mL), with moderate COX-1 (IC50 D 66 mg/mL) andCOX-2 (IC50 D 119 mg/mL) inhibitory effects on the COXpathway. In addition, Pitura (2011) measured the cellular anti-inflammatory activity of seed coat crude extracts of coloredcommon beans (P. vulgaris L.) in LPS-induced murine
macrophage RAW 264.7 cells, the results showed anti-inflam-matory activity of colored bean seed coat. For example, extractsof pinto bean (P. vulgaris cv. Windbreaker) and black bean (P.vulgaris cv. Eclipse) decreased TNF-a levels suggesting anti-inflammatory properties. In another study, Sohn et al. (2014)suggested that anthocyanins extracted from black soybean mayhave anti-inflammatory activity for penile plaque formation inrat Peyronie disease models. Zhang et al. (2014) assessed the invivo effect of 20% navy and black bean (P. vulgaris L.) flours,with different phenolic compound levels and profiles, in amouse model of acute colitis. The results showed that beandiets reduced mRNA expression of colonic inflammatory cyto-kines (IL-6, IL-9, IFN-g, and IL-17A) and increased anti-inflammatory IL-10 (p < 0.05), while simultaneously reducingcirculating cytokines (IL-1b, TNF-a, IFN-g, and IL-17A, p <
0.05) and dextran sulfate sodium (DSS)-induced oxidativestress.
Lectins
Lectins are proteins that have the ability to bind specifically andreversibly to carbohydrates and glycoconjugates without alter-ing the structure of the glycosyl ligand (Leite et al., 2012). Inlegumes, lectins make up about 10% of the total nitrogen of theseeds (Oliveira et al., 2008). Plant lectins can display either pro-or anti-inflammatory actions depending on the administrationroute used via lectin domain interaction (Assreuy et al., 1997;Assreuy et al., 1999; Alencar et al., 1999; Alencar et al., 2004).Leite et al. (2012) purified and characterized lectins in the seedsof butterfly pea (Clitoria fairchildiana) and verified their anti-inflammatory activity. It was observed that lectin had anti-inflammatory activity in the carrageenan induced paw edemainflammation model, in which a 64% diminution in edema wasobserved. Moreover, Ara�ujo et al. (2013) evaluated anti-inflam-matory activity of monocot lectin from the Canna limbataseeds. The lectin showed anti-inflammatory effect with thereduction of inflammation in the formalin test and neutrophilmigration into the peritoneal cavity. Bezerra et al. (2014) char-acterized the anti-inflammatory properties of lectin from Cana-valia boliviana using in vivo model. The paw edema induced bycarrageenan was also inhibited in presence of lectin at 1 mg/kgconcentration. In another study, when soybean agglutinin ispresent in the blood circulation, an inhibitory effect on neutro-phil migration was observed suggesting an anti-inflammatoryeffect (Benjamin et al., 1997). The results showed that soybeanagglutinin (5–200 mg/cavity) injected into rats with differentcavities induced a typical inflammatory response characterizedby dose-dependent exudation and neutrophil migration 4 hafter injection.
Future perspective
The pharmacological relevance of active constituents is fullyjustified by the most recent findings indicating that fruits, vege-tables, and food legumes are the medicinal and nutritionalagents useful for treating a wide range of human disorders. Fur-ther investigations are needed to fully understand the modes ofactions of phytochemicals and to fully exploit their preventiveand therapeutic potential. Phytochemicals definitely deserve
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1267
further studies with regard to biological activity, including stud-ies into mechanism of action and structure-activity relation-ships. Other fruits, vegetables, and food legumes should beinvestigated in terms of a potential source of new chemicalstructures and biological activities. Future research works couldfocus on combining in vitro model, animal model, and humantrials to thoroughly identify the anti-inflammatory propertiesof phytochemicals. In addition, it is difficult to make a judg-ment to say which food is the best for anti-inflammatory dietary therapy based on the literature data pre-sented in this review work, because the investigations weredone by different research groups with different experimentalmodels and methodologies. Therefore, a future in-depth studyis suggested to incorporate these commonly consumed fruits,vegetables and food legumes into one study, and compare theiranti-inflammatory potential based on the same conditions, sothat we can recommend the most potent food to consumers forgaining anti-inflammatory benefits. Processing methods forfruits, vegetables, and food legumes, such as boiling, pressurecooking, roasting, sprouting, and so on, should also be opti-mized to minimize the loss of therapeutic effects. The advancesin biotechnological tools and the research community’s capac-ity to develop imaginative strategies will help in framing afruits, vegetables, and food legumes’ development program forensuring the nutritional security of the world. Moreover, foodlegumes differ in their composition regarding the content andtype of bioactive compounds. Further studies should be aimedat random clinical trials to compare diverse types of foodlegumes to determine the most beneficial for a particular dis-ease prevention and treatment. Although fruits, vegetables, andfood legumes are natural foods and nontoxic substances, thepurified compounds from fruits, vegetables and food legumesmay still have certain potential side-effects, the over-dose usagemay also cause side- effects. Therefore, the further study shouldalso look on this point so that food scientist can give a rationalsuggestion to consumers in either choosing the original fruits,vegetables, and food legumes or choosing the purified com-pounds or processed nutraceuticals from these foods. In addi-tion, there are lack of study on structure-activity relationship ofisolated compounds from fruits, vegetable, and food legumes,this could be one of the future research areas.
Acknowledgments
This project is jointly supported by one grant (project code: UIC201624)from Beijing Normal University-Hong Kong Baptist University UnitedInternational College and one grant (R1005) from Zhuhai Key Laboratoryof Agricultural Product Quality and Food Safety.
Conflict of interest
The authors have declared that there is no conflict of interest.
References
Ali, N. M., Mohd Yusof, H., Yeap, S. K., Ho, W. Y., Beh, B. K., Long, K.,Koh, S. P., Abdullah, M. P., and Alitheen, N. B. (2014). Anti-inflamma-tory and antinociceptive activities of untreated, germinated, and
fermented mung bean aqueous extract. Evid. Based ComplementAlternat. Med. 2014:1–6.
Alencar, N. M., Teixeira, E. H., Assreuy, A. M., Cavada, B. S., Flores, C. A.,and Ribeiro, R. A. (1999). Leguminous lectins as tools for studying therole of sugar residues in leukocyte recruitment. Mediators Inflamm.8:107–113.
Alencar, N. M., Assreuy, A. M., Criddle, D. N., Souza, E. P., Soares, P. M.,Havt, A., Arag~ao, K. S., Bezerra, D. P., Ribeiro, R. A., and Cavada, B. S.(2004). Vatairea macrocarpa lectin induces paw edema with leukocyteinfiltration. Protein Pept. Lett. 11:195–200.
Ara�ujo, T. S., Teixeira, C. S., Falc~ao, M. A., Junior, V. R., Santiago, M. Q.,Benevides, R. G., Delatorre, P., Martins, J. L., Alexandre-Moreira, M.S., Cavada, B. S., Campesatto, E. A., and Rocha, B. A. (2013). Anti-inflammatory and antinociceptive activity of chitin-binding lectin fromCanna limbata seeds. Appl. Biochem. Biotechnol. 171:1944–1955.
Assreuy, A. M., Shibuya, M. D., Martins, G. J., Souza, M. L., Cavada, B. S.,Moreira, R. A., Oliveira, J. T. A., Ribeiro, R. A., and Flores, C. A.(1997). Anti-inflammatory effect of glucose-mannose binding lectinsisolated from Brazilian beans.Mediators Inflamm. 6:201–210.
Assreuy, A. M., Martins, G. J., Moreira, M. E., Brito, G. A., Cavada, B. S.,Ribeiro, R. A., and Flores, C. A. (1999). Prevention ofcyclophosphamide-induced hemorrhagic cystitis by glucose-mannosebinding plant lectins. J. Urol. 161:1988–1993.
Benjamin, C. F., Figueiredo, R. C., Henriques, M. G., and Barja-Fidalgo, C.(1997). Inflammatory and anti-inflammatory effects of soybean aggluti-nin. Braz. J. Med. Biol. Res. 30:873–881.
Bezerra, G. A., Viertlmayr, R., Moura, T. R., Delatorre, P., Rocha, B. A. M.,do Nascimento, K. S., Figueiredo, J. G., Bezerra, I. G., Teixeira, C. S.,Simoes, R. C., Nagano, C. S., de Alencar, N. M. N., Gruber, K., and Cav-ada, B. S. (2014). Structural studies of an anti-inflammatory lectin fromCanavalia boliviana seeds in complex with dimannosides. PLoS ONE.9:e97015.
Bodet, C., La, V. D., Epifano, F., and Grenier, D. (2008). Naringenin hasantiinflammatory properties in macrophage andex vivo human whole-blood models. J. Periodontal Res. 43:400–407.
Boudjou, S., Oomah, B. D., Zaidi, F., and Hosseinian, F. (2013). Phenolicscontent and antioxidant and anti-inflammatory activities of legumefractions. Food Chem. 138:1543–1550.
Chen, L., Teng, H., Xie, Z. L., Cao, H., Cheang, W. S., Skalicka, W. K.,Georgiey, M. I., and Xiao, J. B. (2016). Modifications of dietaryflavonoids towards improved bioactivity: An update on structure-activity relationship. Crit Rev Food Sci. Nutr. DOI: 10.1080/10408398.2016.1196334.
Chien, T. Y., Chen, L. G., Lee, C. J., Lee, F. Y., and Wang, C. C. (2008).Anti-inflammatory constituents of Zingiber zerumbet. Food Chem.110:584–589.
Christensen, L. P. (2009). Galactolipids as potential health promoting com-pounds in vegetable foods. Recent Pat. Food Nutr. Agric. 1:50–58.
Comalada, M., Ballester, I., Bailon, E., Sierra, S., Xaus, J., Galvez, J., deMedina, F. S., and Zarzuelo, A. (2006). Inhibition of pro-inflammatorymarkers in primary bone marrow-derived mouse macrophages by nat-urally occurring flavonoids: Analysis of the structure-activity relation-ship. Biochem. Pharmacol. 72:1010–1021.
Das, A., and Parida, S. K. (2014). Advances in biotechnological applica-tions in three important food legumes. Plant Biotechnol. Rep. 8(2):83–99.
Devi, K. P., Malar, D. S., Nabavi, S. F., Sureda, A., Xiao, J., and Nabavi, S.M., et al. (2015). Kaempferol and inflammation: from chemistry tomedicine. Pharmacol. Res. 99:1–10.
Djordjevic, T. M. (2011). Antioxidant activity and total phenolic content insome cereals and legumes. Int. J. Food Prop. 14(1):175–184.
Du, B., Lin, C. Y., Bian, Z. X., and Xu, B. J. (2015). An insight into anti-inflammatory effects of fungal beta-glucans. Trends Food Sci. Tech.41:49–59.
Duranti, M. (2006). Grain legume proteins and nutraceutical properties.Fitoterapia. 77:67–82.
Etoh, T., Kim, Y. P., Hayashi, M., Suzawa, M., Li, S., Ho, C., andKomiyama, K. (2013). Inhibitory effect of a formulated extract frommultiple citrus peels on LPS-induced inflammation in RAW 246.7macrophages. Func. Food Health Disease. 3:242–253.
1268 F. ZHU ET AL.
Fazio, A., Plastina, P., Meijerink, J., Witkamp, R. F., and Gabriele, B.(2013). Comparative analyses of seeds of wild fruits of Rubus and Sam-bucus species from Southern Italy: Fatty acid composition of the oil,total phenolic content, antioxidant and anti-inflammatory propertiesof the methanolic extracts. Food Chem. 140:817–824.
Frontela-Saseta, C., L�opez-Nicol�as, R., Gonz�alez-Berm�udez, C. A.,Mart�ınez-Graci�a, C., and Ros-Berruezo, G. (2013). Anti-inflammatoryproperties of fruit juices enriched with pine bark extract in anin vitromodel of inflamed human intestinal epithelium: The effect of gastroin-testinal digestion. Food Chem. Toxicol. 53:94–99.
Garc�ıa-Lafuente, A., Moro, C., Manch�on, N., Gonzalo-Ruiz, A., Villares,A., Guillam�on, E., Rostagno, M., and Mateo-Vivaracho, L. (2014). Invitro anti-inflammatory activity of phenolic rich extracts from whiteand red common beans. Food Chem. 161:216–223.
Garc�ıa-Lafuente, A., Guillam�on, E., Villares, A., Rostagno, M. A., andMart�ınez, J. A. (2009). Flavonoids as anti-inflammatory agents: impli-cations in cancer and cardiovascular disease. Inflamm. Res. 58(9):537–552.
Garc�ıa-Mediavilla, V., Crespo, I., Collado, P. S., Esteller, A., S�anchez-Cam-pos, S., Tu~n�on, M. J., and Gonz�alez-Gallego, J. (2007). The anti-inflam-matory flavones quercetin and kaempferol cause inhibition ofinducible nitric oxide synthase, cyclooxygenase-2 and reactive C-pro-tein, and down-regulation of the nuclear factor kappa B pathway inchang liver cells. Eur. J. Pharmacol. 557:221–229.
Guang, G., Chen, J., Sang, S. Y., and Cheng, S. Y. (2014). Biological func-tionality of soyasaponins and soyasapogenols. J. Agric. Food Chem.62:8247–8255.
Ha, S K., Park, H. Y., Eom, H., Kim, Y., and Choi, I. (2012). Narirutin frac-tion from citrus peels attenuates LPS-stimulated inflammatoryresponse through inhibition of NF-k;B and MAPKs activation. FoodChem. Toxicol. 50:3498–3504.
Hern�andez-Ledesma, B., Hsieh, C. C., and de Lumen, B. O. (2009). Antiox-idant and anti-inflammatory properties of cancer preventive peptidelunasin in RAW 264.7 macrophages. Biochem. Biophys. Res. Commun.390:803–808.
Hou, C. C., Chen, Y. P., Wu, J. H., Huang, C. C., Wang, S. Y., Yang, N. S.,and Shyur, L. F. A (2007). galactolipid possesses novel cancer chemo-preventive effects by suppressing inflammatory mediators and mouseB16 melanoma. Cancer Res. 67:6907–6915.
Hsu, C., Tsai, T. H., Li, Y. Y., Wu, W. H., Huang, C. J., and Tsai, P. J.(2012). Wild bitter melon (Momordica charantia Linn. var. abbreviataSer.) extract and its bioactive components suppress Propionibacteriumacnes-induced inflammation. Food Chem. 135:976–984.
Ismail, T., Sestili, P., and Akhtar, S. (2012). Pomegranate peel and fruitextracts: A review of potential anti-inflammatory and anti-infectiveeffects. J. Ethnopharmacol. 143:397–405.
Jiang, J., Kang, T. B., Shim, D. W., Oh, N. H., Kim, T. J., and Lee, K. H.(2013). Indole-3-carbinol inhibits LPS-induced inflammatory responseby blocking TRIF-dependent signaling pathway in macrophages. FoodChem. Toxicol. 57:256–261.
Jiang, Y., Zeng, K. W., David, B., and Massiot, G. (2014). Constituents ofVigna angularis and their in vitro anti-inflammatory activity. Phyto-chemistry. 107:111–118.
Kang, J., Xie, C., Li, Z., Nagarajan, S., Schauss, A. G., Wu, T., and Wu,X. L. (2011). Flavonoids from acai (Euterpe oleracea Mart.) pulpand their antioxidant and antiinflammatory activities. Food Chem.128:152–157.
Kang, J. H., Sung, M. K., Kawada, T., Yoo, H., Kim, Y. K., Kim, J. S., andYu, R. (2005). Soybean saponins suppress the release of proinflamma-tory mediators by LPS-stimulated peritoneal macrophages. CancerLett. 230:219–227.
Kim, H. P., Son, K. H., Chang, H. W., and Kang, S. S. (2004). Anti-inflam-matory plant flavonoids and cellular action mechanisms. J. Pharmacol.Sci. 96(3):229–245.
Kim, K. M., Kwon, Y. G., Chung, H. T., Yun, Y. G., Pae, H. O., Han, J. A.,Ha, K. S., Kim, T. W., and Kim, Y. M. (2003). Methanol extract of Cor-dyceps pruinosa inhibits in vitro and in vivo inflammatory mediatorsby suppressing NF-k;B activation. Toxicol. Appl. Pharm. 190:1–8.
Lau, F. C., Bielinski, D. F., and Joseph, J. A. (2007). Inhibitory effects ofblueberry extract on the production of inflammatory mediators in
lipopolysaccharide-activated BV2 microglia. J. Neurosci. Res. 85:1010–1017.
Lee, I. A., Park, Y. J., Yeo, H. K., Han, M. J., and Kim, D. H. (2010). Soyasa-ponin I attenuates TNBS-Induced colitis in mice by inhibiting NF-k;Bpathway. J. Agric. Food Chem. 58:10929–10934.
Lee, S. I., Kim, B. S., Kim, K. S., Lee, S., Shin, K. S., and Lim, J. S. (2008).Immune-suppressive activity of punicalagin via inhibition of NFATactivation. Biochem. Biophys. Res. Commun. 371:799–803.
Leite, J. F., Assreuy, A. M., Mota, M. R., Bringel, P. H., Lacerda, R. R.,Gomes Vde, M., Cajazeiras, J. B., Nascimento, K. S., Pessoa Hde, L.,Gadelha, C. A., Delatorre, P., Cavada, B. S., and Santi-Gadelha, T.(2012). Antinociceptive and anti-inflammatory effects of a lectin-likesubstance from Clitoria fairchildiana R. Howard seeds. Molecules.17:3277–3290.
Li, X., Zhang, J. Y., Gao, W. Y., and Wang, H. Y. (2012). Study on chemicalcomposition, anti-inflammatory and anti-microbial activities ofextracts from Chinese pear fruit (Pyrus bretschneideri Rehd.). FoodChem. Toxicol. 50:3673–3679.
Li, X., Wang, T., Zhou, B., Gao, W., Cao, J., and Huang, L. (2014). Chemi-cal composition and antioxidant and anti-inflammatory potential ofpeels and flesh from 10 different pear varieties (Pyrus spp.). FoodChem. 152:531–538.
Lin, J. Y., and Tang, C. Y. (2008). Strawberry, loquat, mulberry, andbitter melon juices exhibit prophylactic effects on LPS-inducedinflammation using murine peritoneal macrophages. Food Chem.107:1587–1596.
Liu, C. J., and Lin, J. Y. (2013). Anti-inflammatory effects of phenolicextracts from strawberry and mulberry fruits on cytokine secretion pro-files using mouse primary splenocytes and peritoneal macrophages. Int.Immunopharmacol. 16:165–170.
Luo, J. Q, Cai, W. C., Wu, T., and Xu, B. J. (2016). Phytochemical distribu-tion in hull and cotyledon of adzuki bean and mung bean, and theircontribution to antioxidant activities, anti-inflammatory, and anti-dia-betic effects. Food Chemistry. 201:350–360.
Moise, J. A., Han, S., Gudynaite-Savitch, L., Johnson, D. A., and Miki, B. L.A. (2005). Seed coats: Structure, development, composition, biotech-nology. In Vitro Cell Dev Pl. 41:620–644.
Mueller, D., Triebel, S., Rudakovski, O., and Richling, E. (2013). Influenceof triterpenoids present in apple peel on inflammatory gene expressionassociated with inflammatory bowel disease (IBD). Food Chem.139:339–346.
Mcinnes, I. B., and Georg, S. (2011). The pathogenesis of rheumatoidarthritis. N. Engl. J. Med. 365(5):2205–2219.
Mueller, M., Hobiger, S., and Jungbauer, A. (2010). Anti-inflammatoryactivity of extracts from fruits, herbs and spices. Food Chem. 122:987–996.
Murakami, A., Nakamura, Y., Koshimizu, K., and Ohigashi, H. (1995).Glyceroglycolipids from Citrus hystrix, a traditional herb in Thailand,potently inhibit the tumor-promoting activity of 12-O-tetradecanoyl-phorbol 13-acetate in mouse skin. J. Agric. Food Chem. 43:2779–2783.
Needleman, P., and Isakson, P. C. (1997). The discovery and function ofCOX-2. J. Rheumatol. 49:6–8.
Oliveira, T. M., Delatorre, P., Rocha, B. A. M., Souza, E. P., Nascimento, K.S., Bezerra, G. A., Moura, T. R., Benevides, R. G., Bezerra, E. H. S., Mor-eno, F. B., Freire, V. N., de Azevedo, W. F. Jr., and Cavada, B. S. (2008).Crystal structure of Dioclea rostrata: Insights into understanding thepH-dependent dimer-tetramer equilibrium and the structural basis forcarbohydrate recognition in Diocleinae lectins. J. Struct. Biol. 164:177–182.
Oomah, B. D., Corbe, A., and Balasubramanian, P. (2010). Antioxidantand anti-inflammatory activities of bean (Phaseolus vulgaris L.) hulls. J.Agric. Food Chem. 58:8225–8230.
Ouachrif, A., Khalki, H., Chaib, S., Mountassir, M., Aboufatima, R., Far-ouk, L., Benharraf, A., and Chait, A. (2012). Comparative study of theanti-inflammatory and antinociceptiv eeffects of two varieties of Punicagranatum. Pharma. Biol. 50:429–438.
Park, H. J., Kim, S. J., Park, S. J., Eom, S. H., Gu, G. J., Kim, S. H., andYoun, H. S. (2013). Phenethyl isothiocyanate regulates inflammationthrough suppression of the TRIF-dependent signaling pathway of Toll-like receptors. Life Sci. 92:793–798.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 1269
Park, S., Choi, K. C., Fang, M., Lim, Y. C., Jeon, Y. M., and Lee, J. C. (2011).Red bean extract reduces inflmmation and increases survival murinesepsis model. Food Sci. Biotechnol. 20:1125–1131.
Patto, M. C. V., Amarowicz, R., Aryee, A. N. A., Boye, J. I., and Chung, H.J. (2014). Achievements and challenges in improving the nutritionalquality of food legumes. Crit. Rev. Plant Sci. 34(1):105–143.
Pereira, A., and Maraschin, M. (2015). Banana (Musa spp) from peel topulp: Ethnopharmacology, source of bioactive compounds and its rele-vance for human health. J. Ethnopharmacol. 160:149–163.
Pitura, K. (2011). Evaluation of the antioxidant activity of extracts and fla-vonol glycosides isolated from the seed coats of colored beans (Phaseo-lus vulgaris L.). The University of Manitoba. Master Dissertation.
Rathee, P., Chaudhary, H., Rathee, S., Rathee, D., Kumar, V., and Kohli, K.(2009). Mechanism of action of flavonoids as anti-inflammatory agents:A review. Inflamm Allergy - Drug Targets. 8(3):229–235(7).
Rice-Evans, C. A., and Miller, N. J. (1996). Antioxidant activities of flavo-noids as bioactive components of food. Biochem. Soc. Trans. 24:790–794.
Romier, B., Van De Walle, J., During, A., Larondelle, Y., and Schneider, Y.J. (2008). Modulation of signalling nuclear factor-kappaB activationpathway by polyphenols in human intestinal Caco-2 cells. Br. J. Nutr.100:542–551.
Sohn, D. W., Bae, W. J., Kim, H. S., Kim, S. W., and Kim, S. W. (2014). Theanti-inflammatory and antifibrosis effects of anthocyanin extractedfrom black soybean on a Peyronie disease rat model. Urology. 84:1112–1116.
Sreerama, Y. N., Takahashi, Y., and Yamaki, K. (2012). Phenolic antioxi-dants in some vigna species of legumes and their distinct inhibitoryeffects on a-glucosidase and pancreatic lipase activities. J Food Sci. 77(9):C927–C933.
Terra, X., Valls, J., Vitrac, X., M�errillon, J. M., Arola, L., Ard�evol, A., Blad�e,C., Fernandez-Larrea, J., Pujadas, G., Salvad�o, J., and Blay, M. (2007).Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signalingpathway. J. Agric. Food Chem. 55:4357–4365.
Vernaza, M. G., Dia, V. P., Mejia, E. G., and Chang, Y. K. (2012). Antioxi-dant and antiinflammatory properties of germinated and hydrolysedBrazilian soybean flours. Food Chem. 134:2217–2225.
Wang, B. S., Huang, G. J., Lu, Y. H., and Chang, L. W. (2013). Anti-inflam-matory effects of an aqueous extract of Welsh onion green leaves inmice. Food Chem. 138:751–756.
Xiao, J. B. (2017). Dietary flavonoid aglycones and their glycosides:What show better biological benefits? Crit Rev Food Sci. Nutr. 57:1874–1905.
Xiao, J. B., Capanoglu, E., Jassbi, A. R., Miron, A. (2016). Advance on theflavonoid C-glycosides and health benefits. Crit. Rev Food Sci. Nutr. 56(S1):S29–S45.
Xu, B. J., and Chang, S. K. C. (2009). Total phenolic, phenolic acid, antho-cyanin, flavan-3-ol, and flavonol profiles and antioxidant properties ofpinto and black beans (Phaseolus vulgaris L.) as affected by thermalprocessing. J. Agric. Food Chem. 57:4754–4764.
Xu, B. J., and Chang, S. S. K. (2011). Reduction of antiproliferation capaci-ties, cell-based- antioxidant capacities and phytochemical contents ofcommon beans and soybeans upon thermal processing. Food Chemis-try. 129:974–981.
Yamaguchi, K. K. L., Pereira, L. F. R., Lamar~ao, C. V., Lima, E. S., and daVeiga-Junior, V. F. (2015). Amazon acai: Chemistry and biologicalactivities: A review. Food Chem. 179:137–151.
Yu, T., Ahn, H. M., Shen, T., Yoon, K., Jang, H. J., Lee, Y. J., Yang, H. M.,Kim, J. H., Kim, C., Han, M. H., Cha, S. H., Kim, T. W., Kim, S. Y., Lee,J., and Cho, J. Y. (2011). Anti-inflammatory activity of ethanol extractderived from Phaseolus angularis beans. J. Ethnopharmacol. 137:1197–1206.
Zha, L. Y., Mao, L. M., Lu, X. C., Deng, H., Ye, J. F., Chu, X. W., Sun, S. X.,and Luo, H. J. (2011). Anti-inflammatory effect of soyasaponinsthrough suppressing nitric oxide production in LPS-stimulated RAW264.7 cells by attenuation of NF-k;B-mediated nitric oxide synthaseexpression. Bioorg. Med. Chem. Lett. 21:2415–2418.
Zhang, X. W., Shang, P. P., Qin, F., Zhou, Q., Gao, B. Y., Huang, H. Q.,Yang, H. S., Shi, H. M., and Yu, L. L. (2013). Chemical compositionand antioxidative and anti-inflammatory properties of ten commercialmung bean samples. LWT - Food Sci.Technol. 54:171–178.
Zhang, C., Monk, J. M., Lu, J. T., Zarepoor, L., Wu, W., Liu, R., Pauls, K. P.,Wood, G. A., Robinson, L., Tsao, R., and Power, K. A. (2014). Cookednavy and black bean diets improve biomarkers of colon health andreduce inflammation during colitis. Br. J. Nutr. 111:1549–1563.
Zhu, Q., Liao, C. L., Liu, Y. M., Wang, P. C., Guo, W., He, M. J., andHuang, Z. B. (2012a). Ethanolic extract and water-solublepolysaccharide from Chaenomeles speciosa fruit modulate lipopolysac-charide-induced nitric oxide production in RAW 264.7 macrophagecells. J. Ethnopharmacol. 144:441–447.
Zhu, S., Li, W., Li, J. H., Jundoria, A., Sama, A. E., and Wang, H. (2012b). Itis not just folklore: The aqueous extract of mung bean coat is protectiveagainst sepsis. Evid. Based Complement Alternat. Med. 2012:1–10.
Zia-Ul-Haq, M., Landa, P., Kutil, Z., Qayum, M., and Ahmad, S. (2013).Evaluation of anti-inflammatory activity of selected legumes from Paki-stan: In vitro inhibition of Cyclooxygenase-2. Pak. J. Pharm. Sci.26:185–187.
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