186 Current Nutrition & Food Science, 2010, 6, 186-199

Molecular Mechanism Underlying the Therapeutic Activities of Propolis:

A Critical Review

Tahira Farooqui1,* and Akhlaq A. Farooqui2

Departments of 1Entomology and 2Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH,
43210, USA

Abstract: Propolis, a resinous bee-hive product referred as “bee glue”, is collected from various plant sources, such as
buds of conifer and poplar trees, by honeybees (Apis mellifera). Honeybees blend this resinous non-toxic substance with
their salivary secretions and wax flakes secreted from special glands on their abdomens. Propolis has been used as a heal-
ing agent for thousands of years in folk medicine. There is substantial evidence indicating that propolis exhibits a broad
spectrum of therapeutic (biological/pharmacological) properties such as antimicrobial, anti-oxidant, anti-inflammatory,
immunomodulatory, antitumor, anticancer, anti-ulcer, hepatoprotective, and cardioprotective properties. Propolis contains
more than 200-300 natural compounds. The biological/pharmacological activities of propolis depend on the presence of a
large number of polyphenols, mainly flavonoids (flavonoid aglycones), aromatic acids, phenolic acid esters (caffeates and
ferulates), triterpenes, diterpenic acids and lignanes. The chemical composition and beneficial properties of propolis vary
depending on the plant source, geographic origin and collection time. Present overview is an attempt to discuss the
molecular mechanism(s) underlying the diverse biological effects of propolis.
Keywords: Apis mellifera, propolis, flavonoids, phenolic acids, phenolic acid esters, polyphenols, molecular mechanism.

1. INTRODUCTION [7-9]. The major components of Iranian propolis are aro-

Propolis is derived from two Greek words: "pro" means
before or infront, and "polis" means "city" or “community”.
Aristotle reputedly coined the name propolis for the product
that is involved in defending the city [1]; this is exactly what
propolis serves to the hive. Propolis is a natural resinous hive
product that is manufactured by honeybees (Apis mellifera)
from natural balsamic resins, actively secreted by plants on
leaf buds and barks, in combination with bee wax and other
bee secretions [2]. Honeybees use propolis as a sealant in the
construction of their hives, and for shortening the hive en-
trance, making better defence against intruders [3]. Because
of antimicrobial and anti-inflammatory properties of propo-
lis, inhabitants in bee hives are protected from bacterial, fun-
gal, and viral infections [3].
The chemical composition of propolis is very complex. It
includes pharmacologically active constituents, such as
polyphenols, terpenoids, steroids, and amino acids [1]. The
chemical variability and color of propolis (yellow, green,
brown, and red) depend on its botanical source and age of
the honey preparation [4,5]. Different chemical types of pro-
polis are formulated based on the vegetation of area in which
it is collected. For example, propolis samples from Asia,
Europe and North and South America contain different
chemical substances [4]. The major components of propolis
in Europe and China are flavonoids and phenolic acid esters
[1,6], whereas major components in Brazilian propolis are
terpenoids and prenylated derivatives of coumaric acids
*Address correspondence to this author at the Department of Entomology,
The Ohio State University, Columbus, OH, 43210, USA; Tel: (614) 783-
4369; Fax: (614) 488-0361; Email: farooqui.2@osu.edu
matic acids (benzoic and benzenepropanoic acids), esters of
caffeic and phenylethyl-trans-4-coumaric acids, and flavon-
oids (pinocembrin, chrysin) [10], whereas the main com-
pounds identified in Indian propolis from the Gujarat zone
are fatty acids derivatives [11]. The chemical composition of
propolis samples collected from different areas of Japan and
Korea vary considerably [12-14]. Collectively, these studies
suggest that the chemical nature of propolis varies depending
upon the climate and the vegetation in collected areas. Pro-
polis displays a broad spectrum of biological properties,
which are related to the phenolic composition in flavonoids
and phenolic acids. Together with its bactericidal and
fungicidal characteristics, propolis offers many benefits for
its use in cosmetics and hygienic products. It is added in
toothpastes as a prophylactic component for treating perio-
dontal diseases [15], in cetylpyridinium chloride-based
mouthwashes for improving antimicrobial effect against
Staphylococcus aureus [15], and in skin creams for treating
minor burns [16].
Any variability in plant source, chemical composition,
and unsatisfactory quantification may make it difficult to
determine the quality control of propolis. Therefore, before
using propolis as a therapeutic agent, it is necessary to de-
termine the quality control, including the evaluation of the
“type” of propolis (plant source) and identification of chemi-
cal constituents of propolis by the sensitive chemical meth-
ods [12,13,17-20]. There is a long history of the use of pro-
polis in folk medicine because of its therapeutic properties.
Although, it is well known that propolis contains flavonoids,
phenolic acids, and their esters, but molecular mechanisms
associated with beneficial effects of its components in terms
of signal transduction pathway still remains obscure. The
present review discusses the chemical composition, biologi-

1573-4013/10 $55.00+.00 © 2010 Bentham Science Publishers Ltd.

Propolis and Human Health Current Nutrition & Food Science, 2010, Vol. 6, No. 3 187

cal/pharmacological properties, and molecular mechanism

with special emphasis on selective signal transduction path-
ways-modulated by components of propolis.
2. COMPOSITION OF PROPOLIS
As stated above, the chemical composition of propolis is
quite complex, and varies with time of collection, geographic
origin, local flora, variety of trees and plant species used for
collection [21,22]. Among the types of substances usually
found in raw propolis (Fig. 1) include 50% resin (polypheno-
lic fraction), 30% bee-wax, 10% essential and aromatic oils,
5% bee-pollen, and 5% other substances that include
vitamins such as vitamin A, B1, B2, B6, C, D, E, nicotinic
acid and folic acid as well as macro and trace minerals such
as calcium, magnesium, iron, copper, zinc, manganese, nickel,
cobalt, vanadium and strontium [1,17-19,23]. Depending on
the geographic origin (variabilty in plants and season), pro- Fig. (1). General composition of raw propolis.
polis may contain anywhere between 250-350 constituents.
Major constituents identified in propolis are flavonoides,
phenolic acids and their esters, and terpenes [24]. In addi-
tion, propolis also contains glucosidases. The flavonoids can
be classified into various subgroups such as flavones,
flavanones, flavonols, dihydroflavonols and isoflavones (Fig.
2) [25,26]. The ethanolic extract of propolis includes pheno-
lic constituents such as caffeic acid phenethyl ester (CAPE),
quercetin, luteolin, kaempferol, galangin, apigenin, chrysin,
and naringenin (Fig. 3). The water extract of propolis con-
sists only the soluble part of propolis but contains major con-
stituents including prenylated cinnamic acid derivatives such
as artipillin C, baccharin, and drupanin; caffeoylquinic acid
derivatives such as chlorogenic acid, 3,4-di-caffeoylquinic
acid, and 3,5-di-caffeoylquinic acid, as well as some flavon-
oids (Fig. 4).
Propolis from Europe, China and Argentinea is highly
abundant in chrysin (2-4%), pinocembrin (2-4%), pinobank-
sin-acetate (1.6-3%) and galangin (1-2%) [26]. The total
flavonoid content of propolis may be used as a quality index,
classifying 11–14%, 14–17% or more than 17% as accept-
able, good, and high quality, respectively [26]. Taiwanese
and Japanese propolis are characterized by high levels of
propolins, prenylated flavanone compounds [27,28]. Simi-
larly, number of other compounds have been identified in
propolis based on specific geographic origin and plant
sources [11,29-39]. Thus, chemical variability in propolis
gathered from different phytogeographical and botanical
origins raises a big problem because different propolis sam-
ples exert completely different biological activities. Fig. (2). Structural backbone of lipophilic flavonoids is chemically
derived in various groups, such as flavones, flavanones, flavonols,
3. BIOLOGICAL/PHARMACOLOGICAL PROPER- dihydroflavonols and isoflavones.
TIES OF PROPOLIS
and viruses [32, 37-47]. Brazilian propolis fractions have
Depending upon its chemical composition, propolis pos-
been reported to possess an efficient antibacterial action
sesses antimicrobial (antibacterial, antifungal, antiviral),
mainly towards Gram-positive bacteria [41, 42]. The forma-
anti-oxidative, anti-inflammatory, immunomodulatory, anti-
tion of dental caries is caused by the colonization and accu-
tumor, anti-ulcer, hepatoprotective, and cardioprotective
mulation of oral microorganisms and extracellular polysac-
properties (Fig. 5). Because of multifactorial composition
charides that are synthesized from sucrose by glucosyltrans-
and activities, propolis has been suggested to show potential
ferase of Streptococcus mutans. Ethanolic extract of propo-
benefits for human health.
lis, containing the highest concentrations of pinocembrin and
galangin, has been shown to cause marked inhibition of the
3.1. Antimicrobial Activity
glucosyltransferase activity and reduction in growth of S.
Propolis exerts antimicrobial activity against a wide mutans [43], implicating its potential use in preventing dental
range of microorganisms (Table 1), such as bacteria, fungi caries and oral diseases. Furthermore, Salmonella infection
188 Current Nutrition & Food Science, 2010, Vol. 6, No. 3 Farooqui and Farooqui

OH OH
3'
4' OH
2' HO O
8 1 B
HO O
1' 5'
7 A 2 6'
C 3 OH
6 OH OH O
5 4
O Kaempferol OH
OH
Quercetin OH

HO O
HO O

Luteolin
OH O
OH
OH O
Galangin
HO O
OH

HO O Chrysin
OH O
OH

OH O Apigenin HO O

O Naringenin
OH O
O OH
OCH3

HO O
HO CAPE
OH
OH O Hesperetin

Fig. (3). Chemical structures of major constituents in the ethanol extract of propolis.

Fig. (4). Chemical structures of major constituents in the water extract of propolis. R1, R2, and R3 designate the side chains of quinic acid,
caffeic acid, cinnamic acid derivatives (artepillin C, baccharin, and drupanin), caffeoylquinic acid derivatives (3,4-dicaffeoyl quinic acid and
3,5- dicaffeoyl quinic acid), and chlorgenic acid.
Propolis and Human Health Current Nutrition & Food Science, 2010, Vol. 6, No. 3 189

Table 1. Biological Activities of Propolis Depend on Constituents of Propolis

Activity Constituent References

Antimicrobial Terpenes: diterpenes, triterpenes [32, 37-47]

Antibacterial Chrysin, apigenin, pinocembrin and galangin [41-43]

Antiviral (anti-influenza virus and Polyphenols, flavonoids, phenyl- carboxylic acids, and esters of substituted cinnamic acids
[44-47]
anti-herpes simplex virus type2) (caffeic acid, p-coumaric acid, benzoic acid, galangin, pinocembrin, chrysin)

CAPE, caffeic acid, quercetin, kaempferol, luteolin, chrysin [48,49,66]

Propolins [27,28]
Anti-oxidant
Polyisoprenylated benzophenone [50]
Artepillin C [51]
Caffeoylquinic acid derivatives [52]

Anti-inflammatory CAPE, quercetin, chrysin [76-87]

Immunomodulatory CAPE [88-94]

Hepatoprotective CAPE, chrysin, diterpenes [95-101]

Cardioprotective CAPE, acacetin, chrysin, quercetin [102-108]

Anticancer CAPE, artepillin C, chrysin, quercetin, propolin C and D [71, 109-114]

Artepillin C, caffeic acid, CAPE, quercetin, cinnamic acid derivatives, baccharin, drupanin,
Antitumor [27,115-120]
propolins

Anti-ulcer Caffeic, ferulic, p-coumaric and cinnamic acids, essential oil [121-125]

A water-soluble derivative of propolis, WSDP; caffeic acid, CA; caffeic acid phenethyl ester, CAPE; 1,3-diprenyl-2-hydroxy-cinnamic acid, artepillin C.

(Salmonella enteritidis in food contamination and Salmo-
nella typhimurium in human infections) is a big health prob-
lem all over the world, causing diarrhea, fever, and abdomi-
nal cramps. High concentration of ethanolic extract of propo-
lis significantly inhibits Salmonella growth, suggesting the
possible use of propolis as an alternative control of Salmo-
nella infection. Its strongest antibacterial activity against
Gram-positive and limited action against Gram-negative
bacteria may be due to richness in flavonoids.
Both aqueous and ethanolic extracts of propolis exhibit a
high antiviral activity (Table 1). Although, aqueous and
ethanolic extracts of propolis contain different polyphenols,
flavonoids and phenylcarboxylic acids, aqueous propolis
extract shows a relatively high amount of phenylcarboxylic
acids and low concentration of flavonoids in comparison to
the ethanolic extract [44]. Both propolis extracts exhibit high
levels of antiviral activity against HSV-1 and HSV-2 viruses
[45,46]. Different components of propolis in its extract ex-
hibit higher antiherpetic effect and higher selectivity than
single constituent, therefore topical application of propolis
may be suitable against herpes infection. Collectively, the
cytotoxic and antiherpetic effects of propolis extract against-
antiherpes simplex virus (HSV-1 and HSV-2) as well as anti-
influenza virus [44-47] support its antimicrobial potential.
3.2. Anti-oxidant Activity
Capillary electrophoresis coupled with mass spectrome-
try method and reverse phase high performance liquid chro-
matography have detected different phenolic compounds in
extracts of propolis, including pinobanksin 3-acetate, narin-
genin, pinocembrin, chrysin, daidzein, quercetin 3',7-
dimethyl ether, apigenin, and kaempferid, caffeic acid, cou-
maric acid, ferulic acid, cinnamic acid, aromadendrin-4'-
methyl ether, isosakuranetin, drupanin, artepellin C, bac-
charin, and 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyran
acid, which are rich in anti-oxidant activity [34,48]. Anti-
oxidant activity of flavonoids is due to their ability to reduce
free radical formation, scavenge free radicals and chelate
metal ions [14,49]. Flavonoids found in propolis ethanol
extract (Fig. 3) and propolis water extract (Fig. 4) exhibit
anti-oxidant activity. The position of the geranyl or prenyl
group in the flavonoid skeleton contributes to anti-oxidant
activity [28]. The most abundant polyisoprenylated benzo-
phenone, nemorosone, found in Cuban propolis scavenges
the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical in the
same order of magnitude as
-tocopherol, suggesting that
polyisoprenylated benzophenone exerts anti-oxidant capacity
[50]. The methylation of nemorosone abolishes its anti-
oxidant property, implicating that 1,3-diketone system is an
important region required for anti-oxidant activity. There-
fore, absence of the tautomeric equilibrium or any hindrance
in this region may account for altered anti-oxidant capacity
[50]. Free radical scavenging activity of Taiwanese and
Japanese propolis is strongly correlated with its high content
of propolins [27,28]. Artepillin C (1,3-diprenyl-2-hydroxy-
cinnamic acid) has efficient radical scavenging activity, via
one-step hydrogen atom transfer rather than via electron
transfer [51]. Artepillin C shows radical scavenging activity,
whereas baccharin or drupanin do not (Fig. 4), implicating
that 3-prenyl chain of cinnamic acid may be important for its
anti-oxidative activity [51]. Caffeic acid, a metabolite of
caffeoylquinic acid, exhibits powerful DPPH radical scav-
190 Current Nutrition & Food Science, 2010, Vol. 6, No. 3
Fig. (5). Beneficial properties of propolis.
enging activity, while quinic acid (another metabolite of caf-
feoylquinic acid) does not exhibit such activity (Fig. 4).
However, caffeoylquinic acid derivatives and CAPE appear
to be powerful scavengers of DPPH radical, and their effects
may be partly dependent on the nature of their caffeoyl
groups [52]. Active constituents of propolis with high anti-
oxidant activity are listed in Table 1.
There has been a great deal of discussion and contradic-
tion regarding the structure and anti-oxidant activity re-
quirements for flavonoids in past two decades [53-66]. Fla-
vonoids act as hydrogen donating free radical scavengers,
singlet oxygen quenchers, and metal ion chelators, and these
properties may attribute to the phenolic hydroxyl groups
attached to the ring structures. Flavonoids require (Fig. 6) a
hydroxyl group at carbon 3 of the C- ring and 3’,4’-
dihydroxyl groups of the B- ring for their anti-oxidant activ-
ity, and need a 2–3 carbon double bond, a carbonyl group at
carbon 4 of the C- ring, and two hydroxyl groups at carbons
5 and 7 of the A- ring for anti-inflammatory activity [64].
Recently, Ami et al. (2007) have elegantly reviewed the
current knowledge of the structure-activity relationship
(SAR) and SAR quantification for anti-oxidant activities of
flavonoids [65]. Another issue regarding the effect of meta-
bolic transformation on flavonoid bioactivity has also been
recently addressed [66]. This group has reported that struc-
tural modification of quercetin leaves a profound effect on
the bioactivity due to metabolic transformation, but the SAR
realationship is required for anti-oxidant activity [66].
Based on this model, a relation can be shown between
anti-oxidative activity and SAR of several constituents of
propolis. CAPE, an active component of propolis, has 3,4-
dihydroxyl groups (Fig. 3) on the catechol ring that may con-
tribute to its anti-oxidant activity [67]. Three flavonols,
quercetin, kaemferol and galangin, have a hydroxyl group at
carbon 3 on the C- ring, but differ in the B- ring hydroxyla-
Farooqui and Farooqui
tion patterns (Fig. 3). Quercetin with 3’,4’-dihydroxyl groups
on the B- ring exhibits the strongest anti-oxidant capacity,
followed by kaempferol (4’-monohydroxyl group at the B-
ring) with modest activity, and then galangin that has no
hydroxyl group at the B- ring [64]. Luteolin, apigenin, and
chrysin are flavones that lack a hydroxyl group at carbon 3
on the C- ring, but differ in the B- ring hydroxylation pat-
terns (Fig. 3). Luteolin has 3,4-dihydroxyl groups, apigenin
consists 4-monohydroxyl group, but chrysin lacks hydroxyl
groups at 3’ and 4’ positions at the B- ring. Thus, the relative
order of anti-oxidative activity should be: luteolin > apigenin
> chrysin. In addition, all three flavones should possess
equivalent anti-inflammatory activity because they meet full
SAR for anti-inflammatory activity (Fig. 6). Rezai-Zadeh et
al. (2008) findings that apigenin and luteolin dose-
dependently suppress interferon--induced CD40 expression,
and also markedly reduce microglial tumor necrosis factor
alpha (TNF-) and interleukin-6 (IL-6) production [68] sup-
port SAR for anti-inflammatory activity (Fig. 6). Further-
more, naringenin and hesperetin are two flavanones of very
similar in structure, former possessing 4-hydroxyl and the
later 3-hydroxyl on the B- ring, and both exhibit anti-
oxidant capacity. Naringenin exhibits higher anti-oxidant
capacity than naringin (flavanone glycoside), suggesting that
blockade or removal of the 3-OH group in the C- ring may
result in decreased anti-oxidative property [69]. Naringenin
is structurally identical to apigenin except for the absence of
the 2,3-double bond in the C- ring (Fig. 3) makes it inactive
in inhibiting adhesion molecule expression [64]. Taxifolin
has a hydroxyl group at carbon 3 in the C- ring, dihydroxyl
groups at carbons 3’ and 4’ in the B- ring, and 5 and 7 hy-
droxyl groups in the A- ring and a carbonyl group at carbon
4 of the C- ring, but lacks a 2–3 carbon double bond in the
C- ring. Therefore, it is a strong anti-oxidative agent with
diminished anti-inflammatory activity [66]. However, (-)-
epicatechin lacks both 2,3-double bond and carbonyl group
Propolis and Human Health
Fig. (6). Structure-activity-relationship (SAR) for anti-oxidative and anti-inflammatory activities of flavonoids. Three hydroxyl groups
including one at carbon 3 of the C- ring and dihydroxyl groups at carbons 3’ and 4’ of the B- ring are required for anti-oxidant activity of
flavonoids. A 2–3 carbon double bond and a carbonyl group at carbon 4 of the C- ring, and 5 and 7 hydroxyl groups of the A- ring shown in
the shaded area are responsible for anti-inflammatory activity of flavonoids.
in the C- ring, therefore it exerts strong anti-oxidative activ-
ity but lacks anti-inflammatory activity [66]. These findings
support SAR features (Fig. 6). Artepillin C, an isoprenyl
containing phenolic compound isolated from Brazilian pro-
polis, is an effective anti-oxidant that prevents oxidation of
low density lipoprotein [70]. Lastly, propolins (pren-
ylflavanones; flavonoid compounds with or without hydrated
geranyl side chains) isolated from Taiwanese propolis ex-
hibit strong free radical scavenging activity [71].
Accumulating evidence suggests that both ethanol and
water extracts of propolis exert antioxidative effect through
different mechanisms, including free radical scavenging ac-
tivity, hydrogen donating capability, and metal ion chelating
activity [65]. Flavonoids inhibit oxidative stress and
inflammation by modulating several steps in the signal
transduction pathway. For example, CAPE, one of the most
potent lipophilic anti-oxidant isolated from propolis, inhibits
ROS production by blocking interaction between 5-
lipoxygenase and its substrate [72], retards lipid peroxidation
[73], suppresses nuclear transcription factor kappa B (NF-
B) activation [74], and induces gene transcription for anti-
oxidant enzymes and upregulates heme oxygenase-1 [75].
3.3. Anti-inflammatory Activity
Propolis exerts anti-inflammatory activity (Table 1). It
not only suppresses prostaglandin and leukotriene generation
by inhibiting the expression and activities of cyclooxy-
genases and lipoxygenases (Fig. 7), but also by retarding the
gene expression of nitric oxide synthase, TNF-
-mediated
NF-B activation, and reducing immune response in T cells
[6, 76-84]. Inhibition of NF-B activation may be the mo-
lecular basis for its anti-inflammatory properties of propolis.
Woo et al. (2005) investigated the effect of chrysin on the
expression of cyclooxygenase-2 (COX-2) in lipopolysaccha-
Current Nutrition & Food Science, 2010, Vol. 6, No. 3 191
ride (LPS)-activated Raw 264.7 cells [84]. They reported
that chrysin significantly suppresses the LPS-induced COX-
2 protein and mRNA expression in a dose-dependent man-
ner. The mutational analysis and electrophoretic mobility
shift assay have verified that nuclear factor for IL-6 is re-
sponsible for the chrysin-mediated COX-2 downregulation,
suggesting its anti-inflammatory and anti-carcinogenic prop-
erties [84].
The anti-inflammatory effects of Artepillin C examined
in mice, and in vitro nitric oxide production by RAW 264.7
cells, as well as NF-B activity in HEK 293 cells, indicate
that Artepillin C inhibits prostaglandin E2 synthesis in mice,
decreases nitric oxide inhibition production in RAW 264.7
cells, and reduces NF-B activity in HEK 293 cells [85].
Another study shows that quercetin down-regulates inflam-
matory responses and provides neuroprotection by inhibiting
inducible nitric oxide synthase (iNOS) expression and de-
creasing nitric oxide (NO) production in endotoxin/cytokine-
stimulated microglia [86]. The anti-inflammatory effect of
quercetin is accompanied by the down-regulation of extracel-
lular signal-regulated kinase, c-Jun N-terminal kinase, p38,
Akt, Src, Janus kinase-1, Tyk2, signal transducer and activa-
tor of transcription-1, and NF-B. In addition, quercetin
scavenges free radicals and produces inhibitory effects on
serine/threonine and tyrosine phosphatase activities. Quer-
cetin also disrupts the accumulation of lipid rafts, suggesting
that such anti-inflammatory action may be attributable to its
raft disrupting and anti-oxidant effects [86]. Furthermore, the
effects of water extract of Brazilian green propolis on angio-
genesis, inflammatory cell accumulation and endogenous
cytokines production in sponge implants of mice show that
both anti-inflammatory and anti-angiogenic effects of propo-
lis are associated with cytokine modulation [87]. Collective
evidence suggests that propolis may be used for the treat-
ment of chronic inflammatory human disorders.
192 Current Nutrition & Food Science, 2010, Vol. 6, No. 3 Farooqui and Farooqui

Fig. (7). Signal transduction patways showing generation of ROS, activation of NF-B, redox status, and gene expression in during oxidative
stress. 1, NADPH oxidase; superoxide dismutase 2, catalase; 3, glutathione peroxidase; 4, glutathione reductase; glutathione reductase 5;
cytosolic phospholipase A2 (cPLA2); secretory phospholipase A2 (sPLA2); cyclooxygenase-2 (COX-2), lipoxygenase (LOX); superoxide
dismutase (SOD); nitric oxide synthase (NOS); nitric oxide (NO); peroxy nitrite (OONO-); cytokines, TNF-
and IL-1; reduced glutathione
(GSH); oxidized glutathione (GSSG) and hydrogen peroxide (H2 O2), Nuclear factor-B (NF-B); and Nuclear factor-B response element
(NF-B-RE).

3.4. Immunomodulatory Activity
Immunomodulatory action of propolis has been well
documented (Table 1), but the exact mechanisms of propolis
on immune pathway are still unclear. In vitro and in vivo
assays show the immunomodulatory action of propolis on
murine peritoneal macrophages is not only caused by the
increase in microbicidal activity, but also by an increase in
stimulatory action on the lytic activity of natural killer cells
against tumor cells [88-90]. The ethanolic extracts of propo-
lis stimulate antibody production in sheep red blood cells-
immunized mice [90]. The enzyme, indoleamine 2,3-
dioxygenase, regulates immune responses through the capac-
ity to degrade tryptophan into its metabolites that are respon-
sible for suppressing effector T-cell function and favoring
differentiation of regulatory T cells. Increased dose of etha-
nolic extract of propolis or increased number of its admini-
strations in immunized mouse spleen cells produces an in-
hibitory effect on the formation of the arterial plaques [91].
Toll-like receptors (TLRs) play a crucial role in microbial
recognition and development of the adaptive immune re-
sponses. It is reported that propolis inhibits the initial steps
of the immune response in vivo by downregulating TLR2
and TLR4 expression and the production of pro-
inflammatory cytokines in mice, suggesting propolis modu-
lates the mechanisms of the innate immunity [92]. Suppres-
sion of specific immune response to antigenic load (via die-
tary and/or airborne antigens) and increased tolerance are
normal regulatory events in the homeostasis of the immune
system. Propolis component, CAPE mediates immunomodu-
latory (immune-boosting activity) effect by strengthening
phagocyte activity, and thus increasing the ratio of CD4/CD8
T cells in mice [6,23,89,90]. CAPE exerts strong anti-
inflammatory effects and cell suppression of T lymphocytes
[93], and inhibits store-operated Ca2+ entry channels and K +
channels, which may be an intriguing step of signals activat-
ing immune responses [93]. Effects other than the Ca2+ re-
leased activated Ca2+ current may play a dominant role in
CAPE-mediated immunomodulation. Park et al. (2007)
evaluated the effects of CAPE on the active systemic ana-
phylaxis induced by ovalbumin challenge in mice [94]. After
challenges, control mice develop anaphylactic symptoms
(increased plasma levels of histamine, increased ovalbumin-
specific IgE, marked vascular leakage, and NF-B activa-
tion) and histological changes, including pulmonary edema
and hemorrhage in the renal medullae [94]. In contrast,
CAPE-treated mice show decrease in the plasma levels of
histamine and ovalbumin-specific IgE, and inhibition of NF-
B activation, indicating that CAPE-mediated anti-allergic
effects may be the result of its protective effects against IgE-
mediated allergy [94]. Collective evidence supports the view
that CAPE, a selective inhibitor of NF-B activation, may
provide the molecular basis for its multiple anti-
inflammatory and immunomodulatory activities.
Propolis and Human Health
3.5. Hepatoprotective Activity
Several studies have reported the hepatoprotective effect
of propolis in liver injuries (Table 1). The animal models of
hepatotoxicity can be created by inducing liver damage with
administered carbon tetrachloride (CCl4), or by giving
chronic alcohol to rodents. Lin et al. (1997) induced chronic
alcohol liver injuries in rats by adding alcohol to their daily
diet for four weeks [95]. This group administered different
doses of propolis (ethanol extract, three times/day for three
days, orally) after four weeks' of alcohol intake. The propolis
ethanol extract containing 10 mg/kg significantly decreases
the elevations of serum transaminases, triacylglyceride and
hepatic triacylglyceride, whereas 30 mg/kg shows a remark-
able decrease in the hepatocellular fatty degeneration-
induced by chronic alcohol abuse [95]. As mentioned above,
the chemical composition of propolis varies considerable
with its geographic origins and plant sources. Banskota et al.
(2000) investigated three different biological activities
(DPPH free radical scavenging activity, cytotoxicity and
hepatoprotective activity) in the methanol as well as water
extracts of propolis from Brazil, Peru, The Netherlands and
China [96]. Stronger DPPH free radical scavenging activity
is found in water extracts of six Brazilian and a Chinese pro-
polis than their corresponding methanol extracts, whereas
methanol extracts of Netherlands and Peruvian propolis pos-
sess stronger DPPH free radical scavenging activity than
their corresponding water extracts. However, the methanol
extracts of all propolis samples in this study exhibit stronger
cytotoxicity than the corresponding water extracts; while
almost all samples possess significant hepatoprotective activ-
ity [96]. The hepatoprotective activity of the alcoholic ex-
tract of tropical Brazilian propolis is mainly due to phenolic
compounds, including flavonoids [97]. In the same experi-
mental model, labdane-type diterpenes (isolated from the
methanol extract) also possess significant hepatoprotective
activity [97].
El-Khatib et al. (2002) evaluated the protective effect of
the aqueous propolis extract against CCl4-mediated effects
on hepatocytes in vivo [98]. A decrease in the leakage of the
cytosolic enzyme lactate dehydrogenase, decrease in the
lipid peroxidation and maintenance of cellular reduced glu-
tathione content suggest that the hepatoprotective effect of
propolis may be not only due to anti-oxidant activity, but
also due to the maintenance of cellular GSH content [98].
The duration-dependent hepatoprotective effects of propolis
extract against CCl4-induced liver damage in rats indicate
that propolis reverses CCl4-induced alterations of all parame-
ters (including significant reduction in glycogen contents and
alkaline phosphatase, adenosine triphosphatase, and succinic
dehydrogenase activities, and increased total protein contents
and acid phosphatase activity in liver and kidney) within 6-
24 h of toxicant exposure, indicating the maximal protection
at 24 h post-exposure of CCl4 [99]. Furthermore, CAPE sig-
nificantly inhibits tamoxifen (antagonist of the estrogen re-
ceptor)-induced hepatic reduced glutathione GSH depletion
and accumulation of oxidized glutathione (GSSG) and lipid
peroxidation in liver [100]. Treatment of D-galactosamine-
induced hepatotoxicity with chrysin in rats results in de-
creased activities of hepatic markers enzymes (aspartate
aminotransferase, alanine aminotransferase, alkaline phos-
Current Nutrition & Food Science, 2010, Vol. 6, No. 3 193
phatase and
-glutamyl transpeptidase), decreased lipid per-
oxidation products (thiobarbituric acid reactive substances,
lipid hydroperoxides and conjugated dienes), increased ac-
tivities of free radical scavenging enzymes (superoxide dis-
mutase, catalase and glutathione peroxidase) and increased
levels of anti-oxidants [101]. Collective evidence suggests
that propolis has a marked hepatoprotective potential due to
its composition of flavonoids, phenolic compounds and
diterpenes.
3.6. Cardioprotective Activity
Cardioprotective effects of propolis are mediated through
several propolis components (Table 1). Flavonoids act as
naturally occurring anti-oxidants and iron chelators, there-
fore have been used as cardioprotective agents in doxorubi-
cin-induced cardiotoxicity caused by the formation of oxy-
gen free radicals. However, the underlying mechanism of
action of all flavonoids present in propolis extract is still
ellusive. Myocardial tissue from doxorubicin and/or vin-
blastin-treated rats show a marked increase in malondialde-
hyde production, a depletion of GSH contents, and reduction
of catalase and superoxide dismutase activities [102], sug-
gesting doxorubicin and/or vinblastin toxicity is mediated
through mitochondrial dysfunction that results in increased
ROS formation. Pre-treatment of these rats with propolis
extract administered 4 days prior to doxorubicin and/or vin-
blastin, not only substantially reduces the peroxidative dam-
age in myocardial tissues, but also restores catalase and SOD
activities, supporting the view that polyphenols in propolis
protect heart tissues by blocking the oxidative stress and
restoring mitochondrial dysfunction [102-104]. ROS genera-
tion favors the release of cytochrome c from mitochondria
and consequent formation of the apoptosome complex
through up-regulation of Bax or down-regulation of Bcl-XL
inducing apoptosis [105]. CAPE exerts anti-arrhythmic
effect (reduction in the incidence and duration of ventricular
tachycardia and ventricular fibrillation, as well as decrease in
the mortality) in rats subjected to myocardial ischemia and
ischemia-reperfusion injury [106]. Ethanol extract of propo-
lis at 10-4 dilution exhibits the highest free radical scaveng-
ing activity when compared with vitamin E and quercetin.
These observations support the view that some of the protec-
tive effects of propolis can be attributed to direct scavenging
properties of CAPE [106]. Furthermore, administration of
propolis in diabetic rats decreases levels of blood glucose,
malonaldehyde, NO, NOS, total cholesterol, triglyceride,
low-density lipoprotein cholesterol, very low-density lipo-
protein cholesterol in serum of fasting rats, and increases
serum levels of high density lipoprotein cholesterol and su-
peroxide dismutase, suggesting that propolis regulates the
metabolism of blood glucose and blood lipid leading to de-
creased outputs of lipid peroxidation and scavenging the free
radicals in rats with Diabetes mellitus [107].
In addition, flavonoids in propolis also possess Fe2+
chelating properties [108]. The good scavenging activity
requires the presence of a catechol moiety in the B- ring
along with 3-OH moiety in combination with a 2–3 carbon
double bond in the C- ring of flavonoids, resulting in in-
creased Fe2+ chelation and inhibiting the rate of lipid peroxi-
dation [108]. Thus, chelation raises the level of scavenging
194 Current Nutrition & Food Science, 2010, Vol. 6, No. 3
activity of flavonoids. Collectively, propolis flavonoids may
be potentially useful in protection against doxorubicin-
induced cardiotoxicity in patients.
3.7. Anticancer Activity
Propolis is known to have efficacy in cancer prevention
and treatment (Table 1). Propolins C and D of bee propolis
are powerful inducers of apoptosis in human melanoma cells,
suggesting that they possess anticancer activity [71]. In rats,
effects of feeding flavone, flavanone and flavonol have been
investigated on two steps (initiation and promotion) of afla-
toxin B1-induced hepatocarcinogenesis [109]. Propolis con-
tains several anticancer ingredients: (1) European, Far East
and New Zealand propolis contains CAPE, (2) Brazilian
green propolis has artepillin C (ARC), and (3) Brazilian red
propolis possess medicarpin and 3-hydroxy-8,9-dimethoxyp-
terocarpan [110]. Both CAPE-based and ARC-based propo-
lis extracts selectively block oncogenic serine/threonine-
protein kinase (PAK 1) signaling pathway. More than 70%
of human cancers, such as breast and prostate cancer, require
PAK 1, an enzyme encoded by the PAK1 gene, for their
growth. Green propolis extract produces beneficial effects in
treating these cancers [111]. The chemical composition of
Brazilian red propolis differs from Brazilian green propolis
by the presence of various isoflavononoids, such as medi-
carpin and 3-hydroxy-8,9-dimethoxypterocarpan, which are
known to exert anticancer activities [111]. Six propolins, and
prenylflavanones, isolated and characterized from Taiwanese
propolis, induce apoptosis in human melanoma cells, inhibit
xanthine oxidase, and show a strong capability to scavenge
free radicals [112]. Propolin G from Taiwanese propolis in-
duces apoptosis in glioma and glioblastoma cells. Apoptosis
may be induced through a mitochondrial- and caspase-
dependent pathway. Propolin G possesses free radical scav-
enging activity, therefore it may also exhibit a protective
effect against oxidative stress, contributing to carcinogenesis
[112].
CAPE with structure similar to phenolic acid is a selec-
tive agonist to human estrogen receptor  (hER) rather than
hER
. CAPE does not show any estrogenic effect on estro-
gen receptor-positive breast cancer cells, suggesting its anti-
cancer role by acting as a novel selective estrogen receptor
modulator [113]. Propolis from Turkey shows antitumor
activity in human breast carcinoma cell line (MCF-7), in-
volving propolis effect on all caspases (with stronger im-
munoreactivity for caspase 6 than caspases 8 and 9), suggest-
ing that antitumor activity may be mediated through in-
creased apoptosis [114]. Collectively, propolis may turn out
to be a relatively inexpensive potential therapeutic agent for
cancer treatment.
3.8. Antitumor Activity
Propolis has been shown to possess antitumor action
(Table 1). Characteristic components of propolis are many
kinds of flavonoid aglycones. Artepillin C extracted from
Brazilian propolis has been shown to activate the immune
system and possess antitumor activity [115]. CAPE, a potent
anti-inflammatory agent, isolated from propolis is cytotoxic
to tumor and virally transformed but not to normal cells
[116]. CAPE suppresses the tumor promoter (12-O-
Farooqui and Farooqui
tetradecanoylphorbol-13-acetate; TPA)-mediated oxidative
processes into mice skin/ears [116]. These processes include
polymorphonuclear leukocyte infiltration, hydrogen peroxide
production, and formation of oxidized bases in DNA, which
are essential for tumor promotion. CAPE reduces TPA-
induced H2O2 production in bovine lenses, supporting its
antitumor activity [116]. Mitamura et al. (1996) isolated a
tumoricidal substance (clerodane diterpenoid, PMS-1) from
Brazilian propolis, and observed that PMS-1 reduces the
incidence of skin tumors induced by 7,12-dimethylbenz(a)
anthracene application on mouse skin by inhibiting DNA
synthesis in a de novo pathway, and suppresses the growth of
the tumors also by decreasing DNA synthesis in a salvage
pathway [117].
Propolis is rich in cinnamic acid derivatives. Evaluation
of two related cinnamic acid derivatives (baccharin and dru-
panin) from Brazilian bee propolis for their tumoricidal ac-
tivity in mice allografted with sarcoma S-180 has shown that
these compounds effectively suppress growth of the tumor
cells [118]. Benkovic et al. (2007) have demonstrated the
effect of irinotecan, an anticancer drug, combined with etha-
nolic extract of propolis, and quercetin and naringin (water-
soluble derivates of propolis, WSDP) on the growth of Ehr-
lich ascites tumors and the life span of tumor-bearing mice
[119]. The synergistic action of irinotecan and ethanolic ex-
tract of propolis prolongs the survival time, suggesting that
the combination of ethanolic extract of propolis and irinote-
can may be beneficial for clinical studies in maximizing anti-
tumor activity and minimizing post-chemotherapeutic reac-
tions to the cytostatic drug [119]. Polyphenolic compounds
isolated from propolis (caffeic acid, CAPE, and quercetin)
and WSDP given to mice before tumor cells inoculation have
resulted in significant reduction of the number of tumor nod-
ules in the mouse lung [120], supporting that WSDP, caffeic
acid, CAPE, and quercetin may have potential use in control-
ling tumor growth. Collectively, antitumor activity of propo-
lis and its components may be related to their immunomodu-
latory activity, cytotoxic activity to tumor cells, and induc-
tion of apoptosis and necrosis to tumor cells, resulting in
tumor cell death with out significantly affecting normal cells.
3.9. Anti-ulcer Activity
Pretretment of rats with hydroalcoholic crude extract of
Southeastern Brazilian green propolis (Botanical source:
Baccharis dracunculifolia) in rat model of acute gastric le-
sions (induced by ethanol) and indomethacin results in a
significant reduction in lesion index, total affected area, and
lesion percentage compared to control group, suggesting that
propolis possesses anti-ulcer activity [121,122]. The main
compounds found in Brazilian green propolis include pheno-
lic acids, such as caffeic, ferulic, p-coumaric and cinnamic
acids. Further evaluation of anti-ulcer activity of phenolic
acids shows that Brazilian green propolis components (caf-
feic, ferulic, p-coumaric and cinnamic acids) significantly
diminish the gastric content volume and total acidity and
significantly increase the gastric pH in treated animals com-
pared to control group [123], suggesting that phenolic acids
are responsible for anti-ulcer activity. The main constituents
of aqueous extract of Brazilian green propolis are mono- and
di-O-caffeoylquinic acids [35]. The anti-inflammatory activ-
ity of aqueous extract of Brazilian Green propolis is evalu-
Propolis and Human Health
ated by determining the wound healing parameters, and pro-
polis-treated group of mice at day 4 and day 7 show signifi-
cant reductions in the inflammatory process in comparison
with control group, indicating that propolis constituents are
involved in modulating the wound healing process [35].
Furthermore, studies carried out in experimental model
of ulcerative rats have demonstrated that essential oil of Bac-
charis dracunculifolia plant (composed of non-oxygenated
and oxygenated terpenes) reduce the lesion index, total le-
sion area and the percentage of lesions in ulcerative rats,
colitis-induced by trinitrobenzenosulfonic acid, compared to
control group [124]. Similarly, Brazilian green propolis ex-
tract has been shown to exert anti-ulcer activity by prevent-
ing glutathione depletion and inhibition of lipid peroxidation
[125], implicating its anti-ulcer activity may be due to reduc-
ing colonic oxidative stress. Collective evidence suggests
that propolis displays anti-ulcer activity (Table 1), and has a
potential to be used as a phytotherapeutic agent to treat ul-
cers.
4. MOLECULAR MECHANISM ASSOCIATED WITH
THERAPEUTIC EFFECTS OF PROPOLIS
It is clear from above mentioned studies that propolis
contains components that produce beneficial effects in bacte-
rial infection, allergies, asthma, diabetes, hypertension and
many model systems of several chronic human diseases. It is
speculated that many therapeutic effects of propolis may be
associated with its anti-oxidative, anti-inflammatory and
immunomodulatory activities. A potential hypothetical mo-
lecular mechanism underlying a propolis-mediated protective
effect is shown in Fig. (7). Mitochondrial dysfunction is the
major cause of production of ROS (·O-2, H2O2, and ·OH),
which contributes to the pathogenesis of infection, allergies,
asthma, diabetes, and hypertension. Overproduction of ROS
involves oxidative damage to cellular macromolecules (lip-
ids, proteins and nucleic acids) in tissues undergoing through
oxidative stress (Fig. 7). In addition, several other mecha-
nisms are involved in ROS generation. Enzymic and non-
enzymic oxidation of polyunsaturated fatty acids, such as
arachidonic acid (ARA; 20:4) generates ROS [126]. Interac-
tions of unsaturated fatty acids with the trace metal ion Fe3+
also result in peroxidation of fatty acids and an intensifica-
tion of ROS generation. ROS are also produced by NADPH
oxidase (Fig. 7). It is suggested that in mammalian tissues
including brain, NADPH oxidase is regarded as an important
source of ROS [126-128].
Stimulation of NF-B by ROS results in its translocation
in the nucleus, where it not only facilitates the transcription
of sPLA2. COX-2, NOS, and SOD, but also cytokines (TNF-

and IL-
1) in the nucleus. The expression of TNF-
and
IL-
1 up regulates activities of cPLA2 and sPLA2 through a
positive loop type of mechanism in cytoplasm and neural
membranes. In brain, production of ROS has been implicated
in pathophysiology of many chronic human diseases, includ-
ing Alzheimer disease (AD), Parkinson disease (PD), and
amyotrophic lateral sclerosis (ALS) [129]. In visceral tissues
ROS are closely associated with the pathogenesis of rheuma-
toid arthritis [130], systemic lupus erythematosus [131,132],
sickle cell anemia [133], cardiovascular disease [134], and
various forms of cancer and tumor formation [135-137].
ROS, especially ·OH, when formed in the vicinity of DNA
Current Nutrition & Food Science, 2010, Vol. 6, No. 3 195
can react with DNA, resulting in oxidative damage. ROS-
induced strand breaks in DNA and oxidation of DNA bases
are implicated in the mutagenic and carcinogenic effects of
ROS [138,139].
In addition to oxidative stress, the pathogenesis of men-
tioned diseases also involves inflammatory reactions, which
not only isolate the injured cells from uninjured cells, but
also remove damaged cells, and repair the extracellular ma-
trix. The main mediators of inflammatory reaction are
macrophages in visceral organs and microglia in brain tissue.
Although, the activation of macrophages in visceral organs
and microglia in brain are hallmark of pathology of visceral
and neurodegenerative diseases, but it remains controversial
whether macrophages or microglial cells have beneficial or
detrimental functions in various pathological conditions. The
chronic activation of macrophages may cause neuronal dam-
age through the release of potentially cytotoxic molecules
such as proinflammatory cytokines, eicosanoids, platelet
activating factor, proteinases and complement proteins
[140,141].
Very little is known about molecular mechanisms and in-
ternal and external factors that control and modulate the dy-
namics of acute and chronic inflammation in the body. This
process involves the interplay not only among macrophages,
polymorphonuclear neutrophil (PMN) and endothelial cells,
but also among various lipid mediators that originate from
enzymic and non-enzymic degradation of neural membrane
glycerophospholipids (eicosanoids, platelet activating factor)
sphingolipids (ceramide) and cholesterol (hydroxycholester-
ols) [139-141]. In addition, receptors, like toll like receptors
(TLR) and transcription factors such as peroxisome prolif-
erator-activated receptor (PPAR) and NF-B also play an
important role in modulation of inflammatory processes.
This information on signaling pathway involving inflamma-
tory mediators is beginning to be published [140].
Collective evidence suggests that the inflammatory cas-
cade is an attempt by the body to eliminate the challenge
imposed by the injury or infection, clear the system of the
dead and damaged cells, and rescue the normal functioning
of vital organs. Components of propolis, such as caffeic,
ferulic, p-coumaric and cinnamic acids, CAPE, quercetin,
and chrysin block the generation of inflammatory mediators
(eicosanoids and platelet activating factor) by inhibiting the
expression of cyclooxygenases, lipoxygenases, phospholi-
pase A2, and nitric oxidase synthase [78, 81, 82]. In addition,
some components of propolis also inhibit stimulation of NF-
B (Fig. 7) by blocking it translocation to the nucleus [77-
79]. Recent studies also indicate that propolis prevents and
mitigate diabetes, hypertension and obesity. Although, the
molecular mechanism of beneficial effects of propolis in
obesity remains elusive, but recent studies indicate that oral
administration of propolis extract suppresses overall weight
gain in mice, the accumulation of visceral adipose tissue
weight, and the increase in serum and liver triglycerides that
caused by feeding a high-fat diet to C57BL/6N mice [142].
The antihypertensive effects of propolis are due to the pres-
ence of 4,5-di-O-caffeoylquinic, 3,5-di-O-caffeoylquinic,
and 3,4-di-O-caffeoylquinic acids [143]. Real-time PCR
studies indicate that the anti-obesity effects of propolis ex-
tract can be attributed to reduction in expression of fatty acid
196 Current Nutrition & Food Science, 2010, Vol. 6, No. 3
synthesis genes in the liver [142]. In addition, propolis ex-
tracts retard body weight gain and liver triglycerides in high-
fat diet-mediated obesity. Since it is becoming increasingly
evident that accumulation of visceral adipose tissue and hy-
perlipidemia can induce metabolic syndrome, studies on the
effect of propolis in C77BL/6N mice suggest that propolis
extract may prevent and mitigate metabolic syndrome in-
duced by excessive intake of a high-fat diet, and that this
may occur by down-regulating lipid metabolism-related gene
expression [142]. More studies are needed on antihyperten-
sive and anti-obesity effects of propolis.
5. SIDE EFFECTS OF PROPOLIS
Bee keepers have long noticed sensitization to propolis,
resulting in allergic reactions with skin and mucous mem-
brane irritations. Multiple case of contact dermatitis, such as
erythema, eczema, vesiculitis, and pruritis have also been
reported with propolis, but it is still considered as a relatively
nontoxic substance possibly because flavonoids are the main
chemical constituents [1, 6, 23]. The complete information
regarding its toxicity remains elusive. Forty-five days sub-
chronic toxicity of oral propolis extract investigated in male
rats demonstrates no significant behavioral and clinical tox-
icity in animals, however, hematologic, blood biochemistry
and histopathologic data show some significant differences
between the groups of animals [144]. The aqueous extract of
propolis is formulated as a nutritional food product. When
administered as an adjuvant to therapy to patients (with mild
to moderate asthma), it shows significant reduction in pro-
inflammatory cytokines, prostaglandins and leukotrienes,
suggesting that aqueous propolis extract may be used as an
adjuvant to therapy in asthmatic patients [77]. Topical use of
5% preparation of propolis in recurrent vaginitis study re-
lieves 61% of patients, suggesting its potential use as an al-
ternative treatment for chronic vaginal infection [145]. A
preventive effect of a product containing Echinacea (herb),
propolis, and vitamin C has been observed on the incidences
of respiratory tract infections [146]. Propolis is a potent sen-
sitizer and should not be used in patients with an allergic
predisposition, in particular an allergy to pollen. Therefore,
healthcare practitioners and public should be aware of the
risk of allergic reactions to propolis.
6. CONCLUSIONS
Propolis is a resinous natural hive product derived from
plant exudates. It has been used as a traditional remedy for
various diseases due to biological and pharmacological ac-
tivities. Although, more than 350 constituents have been
identified in propolis samples, but its biological activity is
mainly due to few substances (such as flavonoids, terpenes,
caffeic, ferulic, CAPE, and cumaric acids and esters). Propo-
lis has a wide multispectrum of properties such as antimicro-
bial activity against a wide range of microorganisms (bacte-
ria, fungi and viruses), anti-inflammatory, anaesthetic, heal-
ing, vasoprotective, anti-oxidant, antitumor, anti-ulcer, hepa-
toprotective and immunomodulatory activities. Propolis is
becoming increasingly popular because of its potential role
in contributing to human health. In spite of its beneficial
activities, the most challenging problem is because of uncer-
tainty of its correct dosage and safety. Since chemical com-
Farooqui and Farooqui
position of propolis varies greatly due to differences in time
of collection, vegetation and geographic location, therefore
biological activities of propolis gathered from different phy-
togeographical areas and time of collection will also vary
greatly, therefore it will be a difficult task to define the right
dosage. Furthermore, few individuals exhibit hypersensitiv-
ity to propolis (adverse effects such as rhinitis, conjunctivi-
tis, skin rashes and bronchospasm), therefore individuals
who are allergic or hypersensitive to any of its components
have to avoid using propolis or its supplements.
In conclusion, based on overall findings, it can be sug-
gested that inhibition of ROS formation by propolis and its
components provides a potential molecular basis for the pro-
tective actions of propolis not only through the retardation of
NF-
B activation, inhibition of eicosanoid synthesis, and
reduction in expression of various inflammatory cytokines in
the nucleus, but also through the inhibition of oxidative
damage to proteins, lipids, DNA/RNA and carbohydrates.
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