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Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases

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Bees are arthropods of Hymenoptera order and are classified into two groups based on their type of life: solitary and social life. Propolis is produced by bees that live socially, from the harvesting of products derived from plants and used to seal and protect the hive against intruders and natural phenomena [1]. Propolis term derives from the Greek Pro, "opposite, the entry" and polis, "city or community" [2,3]. Propolis is a natural substance collected by Apis mellifera bees in several plant species. It has been used in folk medicine for centuries [2,4]. Characteristically, it is a lipophilic material, hard and brittle when cold, but soft, flexible and very sticky when warm. Hence the name "beeswax" [5]. It has characteristic odor and shows adhesive properties of oils and interact strongly with skin proteins [6]. The composition of propolis is complex [7,8].
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Chapter 7
Propolis: Alternative Medicine for the Treatment of Oral
Microbial Diseases
Vagner Rodrigues Santos
Additional information is available at the end of the chapter
http://dx.doi.org/10.5772/54003
1. Introduction
Bees are arthropods of Hymenoptera order and are classified into two groups based on their
type of life: solitary and social life. Propolis is produced by bees that live socially, from the
harvesting of products derived from plants and used to seal and protect the hive against
intruders and natural phenomena [1]. Propolis term derives from the Greek Pro, "opposite, the
entry" and polis, "city or community" [2,3]. Propolis is a natural substance collected by Apis
mellifera bees in several plant species. It has been used in folk medicine for centuries [2,4].
Characteristically, it is a lipophilic material, hard and brittle when cold, but soft, flexible and
very sticky when warm. Hence the name "beeswax" [5]. It has characteristic odor and shows
adhesive properties of oils and interact strongly with skin proteins [6]. The composition of
propolis is complex [7,8]. Some factors, such as the botanical origin of propolis and its time of
collection can influence the chemical composition of this resinous material [9]. The color of
propolis varies from yellowish green to dark brown, depending on location - savannah,
tropical forests, desert, coastal and mountainous regions - where it is produced. [10,11,12].
Propolis is used by bees to protect against the entry of microorganisms, fungi and bacteria in
the hive, and as a sealing material for preventing the entry of light and moisture inside. It is
also used to line the comb, to allow the deposition of eggs by the queen, and to embalm small
dead animals (beetles and insects) that usually bees could not take into the hive, preventing
its putrefaction.3,5,7].
Interest in the pharmacological action of natural products has grown and found significant
popular acceptance. Among these products, propolis has been highlighted due to its applica‐
bility in the food industry and cosmetics, to be used as the active ingredient in several products,
among which include toothpastes and skin lotions [13]. Also available in the form of a capsule
(pure or combined), extract (hydroalcoholic or glycolic acid), mouthwash (combined with
© 2012 Santos; licensee InTech. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
melissa, sage, mallow and / or rosemary), lozenges, creams and powders (for use in or gargling
internal use, once dissolved in water) [2].
Regarding the ethnobotanical aspect, propolis is one of the few "natural remedies" that
continue to be used for a long period by different civilizations [14]. Propolis is widely used in
popular medicine, especially in communities with inadequate public health conditions[15]. It
was noticed that it can be more effective and less toxic than certain compounds. Significant
decrease in H₂O₂-induced DNA damage in cultures treated with propolis demonstrated
antioxidant activity of phenolic components found in propolis may contribute to reduce the
DNA damage induced by H₂O₂ [16].
2. History
Propolis is a natural remedy that has been used extensively since antiquity. The Egyp‐
tians, who knew very well the anti-putrefactive properties of propolis, used it for em‐
balming [17]. It was recognized for its medicinal properties by Greek and Roman
physicians, such as Aristotle, Dioscorides, Pliny and Galen. The drug was used as an anti‐
septic and healing in the treatment of wounds and as a mouthwash, and its use in the
Middle Ages perpetuated among Arab doctors [2]. Also, it was widely used in the form
of ointment and cream in the treatment of wounds in battle field, because of their heal‐
ing effect. This healing propolis property known as "Balm of Gilead," is also mentioned in
the Holy Bible [18]. From the pharmacological point of view, propolis has been used as
solid; in an ointment based on vaseline, lanolin, olive oil or butter, and in the form of al‐
coholic extract and hydroalcoholic solution. The proportion propolis/carrier may vary, in
order to obtain bacteriostatic or bactericidal results [19]. In the 1980s and 1990s, a great
number of publications occurred worldwide, highlighting Japan in number of published
papers followed by Brazil and Bulgaria [6]. In Dentistry, there are studies investigating
the pharmacological activity of propolissome situations, such as gingivitis, periodontitis,
oral ulcers, pulp mummification in dogs' teeth and dental plaque and caries in rats [19].
Also, it has been used in dressings of pre and post-surgical treatment, oral candididosis,
oral herpes virouses and oral hygiene. There was also the investigation of antiseptic and
healing properties of propolis in subjects admitted to various hospitals and the results
were extremely positive [20]. Thus, this natural product revealed great interest for the
treatment of oral diseases [21]. Internationally, the first licensed commercial product con‐
taining propolis was registered in Romania in 1965. Worldwide, in the same period ana‐
lyzed, it was found a total of 239 commercial licenses. In the 1980s, commercial licenses
were predominant in the former USSR and satellite countries. Currently, 43% of commer‐
cial licenses are Japanese origin and 6.2% of them are products for dental treatment. In Ja‐
pan, the scientific productivity reported for propolis increased 660% between the 1980
and 1990 [22]. The global interest in propolis research increased considerably in relation
to its various biological properties [23-27]. Another incentive for conducting research on
propolis is a high value on the international market, mainly in Japan, where a bottle of
ethanol extract is sold at prices ten times higher than that prevailing in Brazil. Brazil is
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considered the third largest producer of propolis in the world, behind Russia and China
only. Japan’s interest for the Brazilian propolis is due to its therapeutic and organoleptic
properties, and also the presence of minor amounts of heavy metals and other environ‐
mental pollutants [28,29]. In the last thirty years, various studies and scientific research
were performed to clarify the medicinal properties attributed to propolis [30,31].
3. Classification / rating
There was an attempt to classify the Brazilian propolis into twelve types according to physical-
chemical properties and geographical reports. However, to date, only three types of propolis
had their botanical origin identified. The main types of botanical origin are South (three),
Northeast (six) and Southeast (twelve), and they were reported as resins from Populus sp.,
Hyptis divaricata and Baccharis dracunculifolia (Figure 5), respectively. An attempt to classify
propolis produced in Brazil according to botanical origin and chemical composition [32] has
recognized 12 different types. It was suggested that Hyptis divaricata is the resin source of
northeastern propolis, Baccharis dracunculifolia of southeastern propolis and poplar (Populus
nigra) of southern propolis. This study by Park et al. [32] is indicative that just stating that a
certain sample corresponds to ‘Brazilian propolis’ hardly means anything indicative of
physical, chemical and biological characteristics, because a wide diversity of propolis types
exist in a country as large as Brazil, housing a wide plant diversity and a complex honeybee
genetic variation [3]. The different compounds present in Brazilian propolis were identified
and quantified using high performance liquid chromatography (HPLC) technique. Established
the process of separation by liquid chromatography, capable of identifying the major compo‐
nents of propolis samples (primary marker). Through the technique of HPLC and quantifica‐
tion of compounds identified by it, it was established a classification for Brazilian propolis
based on the presence of markers (Table 1 and Table 2). The main feature of this classification
relates to the speed in which this product bee can reach the market, from the field to the
pharmaceutical and cosmetic industries, encouraging the use of these typing for the manu‐
facture of their medicines and cosmetics, with established quality control, since all of these
markers were separated in a concentration range types. That is, the classification is quantita‐
tive. Another important factor is that the classification will be possible to manufacture
pharmaceuticals, cosmetics and oral hygiene products knowing the propolis type used and
the quantities of bioactive components, features never reported before in publications and
patents on propolis [33]. The Brazilian Cerrado is one of the richest areas in Baccharis sp. These
plants are a group of woody perennial shrubs, which are dioecious with male and female
inflorescences appearing on separate plants. Of the 30 different species of Baccharis, Baccharis
dracunculifolia is the dominant source of propolis in southeastern Brazil (Sao Paulo State and
Minas Gerais State), where most of propolis based products sold are produced [34]. Recently,
it was founded a red type of propolis in hives located in mangrove areas in the Northeast. It
was observed that bees collect exudate from the surface of red Dalbergia ecastophyllum
(Linnaeus, Taubert) (Figure 6). Analysis and comparision of plant exudates and propolis
samples demonstrate that the chromatographic profiles are exactly the same as the one found
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for D. ecastophyllum [35]. The best way to find the plant origin of propolis would be by
comparing the chemical composition of propolis with the alleged plant origin [36]. World
Propolis constituents of are shown in Table 3.
4. Chemical composition
Table 1 and Table 2 show the chemical markers constituents of green and red Brazilian
propolis, respectively, while Table 3 shows the chemical composition of various types of
world propolis. The highest concentration of phenolic compounds was obtained using sol‐
vents with lower concentrations of ethanol and higher concentrations of crude propolis,
but the highest concentration of flavonoids in the extract was obtained with higher con‐
centrations of ethanol in the solvent [11]. Over 300 chemical compounds are described in
various propolis origins [22]. Among the chemicals constituents, we can include waxes,
resins, balsams, oils and ether, pollen and organic material. The proportion of these sub‐
stances varies and depends on the place and period of collection [5,37]. The collected
propolis in a bee hive, also known as crude propolis, in its basic composition, contains
about 50% of plant resins, 30% of beeswax, 10% essential oils, 5% pollen, 5% debris of
wood and earth [7,14,6]. Propolis also contains various organic acids, considerable
amount of minerals (including, manganese, zinc, calcium, phosphorus, copper), vitamins
B1, B2, B6, C and E, acids (nicotinic acid and pantothenic acid) and aminoacids [5,7,11,38].
These constitutive features may vary by region and period of the year [39, 40].
Compounds mg/g
1 Coumaric acid 3.56
2 Cinnamic acid 1.66
3 Quercetin 1.38
4 Kaempferol 1.77
5 Isorhamnetin 0,91
6 Sakuranetin 5.57
7 Pinobanskin-3-acetate 13.92
8 Chrysin 3.51
9 Galangin 9.75
10 Kaempferide 11.60
11 Artepillin C
(3,5-diprenyl-4-hydroxycinnamic acid) 82.96
BGP from Baccharis dracunculifoila (SBN97). HPLC test (Park et al.) [32].
Table 1. Chemical constituents markers of Brazilian green propolis sample
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Number Compounds Contents (mg/g)
01 Rutin 0.7
02 Liquiritigenin 1.8
03 Daidzein 0.3
04 Pinobanksin 1.7
05 Quercetin 0.5
06 Luteolin 1.2
07 Dalbergin 0.4
08 Isoliquiritigenin 4.8
09 Formononetin 10.2
10 Pinocembrin 3.3
11 Pinobanksin-3-acetate 1.7
12 Biochanin A 0.5
from Dalbergia ecastophyllum (Alencar et al.) [41]
Table 2. Flavonoids and other chemical constituents of Brazilian red propolis
Compounds (percentage of content) Authors
Fatty and aliphatic acids
(24–26%) Flavonoids (18–20%) Microelements (0.5–2.0%)
Burdok et al. [7]
Maciejewicz et al [43]
Park et al. [32]
Kumazawa et al.[44]
Salatino et al. [3]
Ozkul et al.[45]
Eremia et al.[46]
Machado et al.[47]
Vandor-Unlu et al.[48]
Wang et al.[49]
Butanedioic acid (Succinic
acid) Astaxanthin Aluminum (Al)
Propanoic acid (Propionic
acid) Apigenin Copper (Cu)
Decanoic acid (Capric acid) Chrysin Magnesium (Mg)
Undecanoic acid Tectochrysin Zinc (Zn)
Malic acid Pinobanksin Silicon (Si)
D-Arabinoic acid Squalene Iron (Fe)
Tartaric acid Pinostrobin chalcone Manganese (Mn)
Gluconic acid Pinocembrin Tin (Sn)
α-D-Glucopyranuronic acid Genkwanin Nickel (Ni)
Octadecanoic acid (Stearic
acid) Galangin Chrome (Cr)
β-D-Glucopyranuronic acid Acacetin
9,12-Octadecadienoic acid Kaemferide
Tetradecanoic acid Rhamnocitrin
Pentanedioic acid 7,4’-dimethoxyflavone
Glutamic acid 5-hydroxy-4’7-dimethoxyflavone
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Compounds (percentage of content) Authors
2,3,4-trihydroxy butyric acid 5,7-
dihydroxy-3,4’dihydroxyflavone
Phosphoric acid 3,5-dihydroxy-7,4’-
dimethoxyflavone
Isoferulic acid
Sugars (15–18%) Others (21–27%)
Sorbopyranose Cyclohexanone
D-Erythrotetrofuranose 3-methyl,antitricyclo undec-3-en
10-one
D-Altrose Cyclohexane
D-Glucose Cyclopentene
Arabinopyranose 5-n-propyl-1,3
dihydroxybenzene
d-Arabinose Butane
α-D-Galactopyranose 2(3H)-Furanone
Maltose L-Proline
α-D-Glucopyranoside 2-Furanacetaldehyde
D-Fructose 2,5-is-3-phenyl-7-
pyrazolopyrimidine
Aromatic acids (5–10%) Esters (2–6%) Cliogoinol methyl derivative
Benzoic acid Caffeic acid phenethyl ester Fluphenazine
Caffeic acid 4,3-Acetyloxycaffeate 4,8-Propanoborepinoxadiborole
Ferulic acid, Cinnamic acid 1,3,8-Trihydroxy-6-
methylanthraquinone
Cinnamic acid 3,4 dimethoxy-trimethylsilyl ester 1-5-oxo-4,4-diphenyl-2-
imidazolin-2-yl guanidine
3-Methoxy-4-cinnamate 3,1,2-Azaazoniaboratine/
Piperonal
Cinnamic acid 4 methoxy 3 TMS ester 3-
Cyclohexene
2-propenoic acid methyl ester 1H-Indole
Alcohol and terpens (2–
3.3%) 1H- Vitamins (2–4%) Indole-3-one
Glycerol A, B1, B2, E, C, PP 2-Furanacetaldehyde
Erythritol Guanidine
α-Cedrol 2(3H)Furanone
Xylitol 1,3,8-trihydroxy-6-
meyhylanthraquinone
Germanicol
Stigmast-22-en-3-ol
Pentitol
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Compounds (percentage of content) Authors
Ribitol
Vanilethanediol
Bicyclohept-3-en-2-ol
Farneso
Table 3. Propolis constituents according to Shawicka et al.[42].
However, the plant determines the chemical composition of propolis [4,39,40]. Today there are
various substances known in propolis with distinct chemical structures from following classes:
alcohols, aldehydes, aliphatic acids, aliphatic esters, amino acids, aromatic acids, aromatic
esters, flavonoids, hydrocarbohydrates esters, ethers, fatty acids, ketones, terpenoids, steroids
and sugars [21].The first studies to identify the active elements of propolis were performed in
1911 by researchers in Germany [50]: vanillin, cinnamic acid and alcohol. In the 1970s, [51]
succeeded in isolating and identifying eleven elements, especially the most important type
flavonoids, mainly flavones, flavonols and flavonones, terpenes, alpha-aceto butilenol and
isovanillin. At the same time, [52] it was identified the unsaturated aromatic acids such as
caffeic and ferulic acids. In the same decade, Kadakov et al.[53] reported the presence of
thirteen amino acids in samples of propolis. The therapeutic effects are attributed to various
phenolic compounds whichmake up the green propolis, which are widely distributed in plant
kingdom. These flavonoids can be considered the main compounds [7,8], and also some
phenolic acids and their esters, phenolic aldehydes, alcohols and ketones [54]. Flavonoids and
caffeic acid phenethyl ester (CAPE) are phenolic compounds which have the ability to inhibit
the growth and cell division and to increase membrane permeability interfering with microbial
cell motility [13]. Despite being the most studied components of propolis, flavonoids are not
solely responsible for the pharmacological properties. Several other components have been
related to the medicinal properties of propolis [55]. Propolis from Europe and China contains
many flavonoids and phenolic acids esters. Flavonoids are present only in small quantities in
Brazilian propolis. The major components of propolis of Brazilian origin are terpenoids and
ñ-coumarin prenylated acid derivatives [39]. In Southeastern Brazil there is plenty of the
botanical species for production of green resin, which is the Baccharis dracunculifolia, also called
"Rosemary's field", or "broom", which is a plant species typical of the Americas, due to the
necessity of acid soil to grow. Rosemary easily develops in Brazil, both in planted areas and
in abandoned spaces [34, 3,56]. The biodiversity needs to be investigated as a source of new
bioactive substances, such as cinnamic acid derivatives, especially artepilin C, flavonoids and
other pharmacological or functional properties [36].The renewed interest on the composition
of Brazilian propolis is due to the fact that Brazil has a very diverse flora, tropical climate and
Africanized Apis mellifera bees species that produce propolis during the period from April to
September [5,32]. The typical constituents of Brazilian green propolis from Baccharis dracun‐
culifolia are derived prenylated cafeochemic acid and cinnamic acid derivatives, such as
artepilin C and baccharin. Brazilian green propolis is chemically different because it contains
not only prenylateds of cinnamic acid, but also triterpenoid [57]. In dealing with the chemical
composition and biological activity of green propolis, one can not point to a component of a
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particular substance or class of substances that could be responsible for their distinct phar‐
macological activities. Isoliquiritigenin, liquiritigenin and naringenin, isoflavones, isoflavans
and pterocarpans were detected in Cuban Red Propolis, Brazilian Red Propolis (BRP) and
Dalbergia ecastophylum extract (DEE), whereas polyisoprenylated benzophenones guttiferone
E/xanthochymol and oblongifolin A were detected only in BRP. Pigments responsible for the
red color of DEE and red propolis were also identified as two C30 isoflavans, the new retusa‐
purpurin A and retusapurpurin B [10]. Obviously, different samples at different combinations
of substances are essential for the biological activity of propolis [58,14]. It is important to note
that all investigations on the antibacterial activity of specific substances isolated from propolis
showed that a single component does not have an activity greater than the total extract [59].
The chemical properties of propolis are of great relevance considering its pharmacological
value as a natural mixture and as a powerful source of new antimicrobial agents, antifungal,
antiviral and individual compounds [58, 60].
5. Therapeutic properties of propolis
Currently, it is known that Brazilian propolis shows several biological activities, such as
antimicrobial, antiinflammatory, immunomodulatory, among others [12]. The composition of
propolis is very complex. We can observe the following: antibacterial activity, conferred by
the presence of flavonoids, aromatic acids and esters in its composition; bactericidal action
resulting from the presence of cinnamic acid and coumarin; in vitro antiviral activity (herpes
simplex, influenza), due to the action of flavonoids and aromatic acids derivatives, antiulcer
(assistance in healing), immunostimulating, hypotensive and cytostatic actions [21]. The
methods of extraction of propolis may influence its activity, from different solvents at different
soluble extract components [6,61]. The composition of propolis can vary according to the
geographic locations from where the bees obtained the ingredients. Two main immunopotent
chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. CAPE
and artepillin C have been shown to exert immunosuppressive function on T lymphocyte
subsets but paradoxically they activation macrophage function. On the other hand, they also
have potential antitumor properties by different postulated mechanisms such as suppressing
cancer cells proliferation via its anti-inflammatory effects; decreasing the cancer stem cell
populations; blocking specific oncogene signaling pathways; exerting antiangiogenic effects;
and modulating the tumor microenvironment[62]. The good bioavailability by the oral route
and good historical safety profile makes propolis an ideal adjuvant agent for future immuno‐
modulatory or anticancer regimens. However, standardized quality controls and good design
clinical trials are essential before either propolis or its active ingredients can be adopted
routinely in our future therapeutic armamentarium [62].
5.1. Anti-inflammatory activity
As an anti-inflammatory agent, green propolis is known to inhibit the prostaglandin synthesis,
activate the thymus gland, help the immune system by promoting the phagocytic activity,
stimulating cellular immunity, and increasing healing effects on epithelial tissue. Additionally,
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the propolis contains elements such as iron and zinc, which are important for the synthesis of
collagen [63,35]. Recently it was reported that Artepillin C has an inhibitory effect on nitric
oxide and prostaglandin E2 by modulating NF-êâ using the macrophage cell line RAW 264.7
[64]. The anti-inflammatory activity observed in green propolis seems to be due to the presence
of prenylated flavonoids and cinnamic acid. These compounds have inhibitory activity against
cyclooxygenase (COX) and lipooxygenase. It also appears that the caffeic acid phenethyl ester
(CAPE) has anti-inflammatory activity by inhibiting the release of arachidonic acid from
cellular membrane, removing the activities of COX-1 and COX-2 [65, 66]. Propolis also exhibits
anti-inflammatory effects against models of acute and chronic inflammation (formaldehyde
and adjuvant-induced arthritis, carrageenin and PGE 2, induced paw edema and granuloma
pellete cotton). The exact mechanism of anti-inflammatory action of propolis is still unclear [2].
Treatment with 50 µM CAPE significantly reduced the levels of leptin (p<0.05), resistin (p<0.05)
and tumor necrosis factor (TNF)-alpha (p<0.05) which are known to aid adipocytokines
production in adipocytes. CAPE has inhibitory effects on 3T3-L1 mouse fibroblast differen‐
tiation to adipocytes. In 3T3-L1 cells, treatment of CAPE decreased the triglyceride deposition
similar to resveratrol, which is known to have an inhibitory effect on 3T3-L1 differentiation to
adipocytes. In conclusion, we found that CAPE suppresses the production and secretion of
adipocytokines from mature adipocytes in 3T3-L1 cells [67]. The crude hexane and dichloro‐
methane extracts of propolis displayed antiproliferative/cytotoxic activities with IC50 values
against the five cancer cell lines ranging from 41.3 to 52.4 µg/ml and from 43.8 to 53.5 µg/ml,
respectively. Two main bioactive components were isolated, one cardanol and one cardol, with
broadly similar in vitro antiproliferation/cytotoxicity IC(50) values against the five cancer cell
lines and the control Hs27 cell line, ranging from 10.8 to 29.3 µg/ml for the cardanol and < 3.13
to 5.97 µg/ml (6.82 - 13.0 µM) for the cardol. Moreover, both compounds induced cytotoxicity
and cell death without DNA fragmentation in the cancer cells, but only an antiproliferation
response in the the non-transformed human foreskin fibroblast cell line
(Hs27, ATCC No. CRL 1634) used as a comparative control.However, these compounds did
not account for the net antiproliferation/cytotoxic activity of the crude extracts suggesting the
existence of other potent compounds or synergistic interactions in the propolis extracts. This
is the first report that A. mellifera propolis contains at least two potentially new compounds (a
cardanol and a cardol) with potential anti-cancer bioactivity. Both could be alternative
antiproliferative agents for future development as anti-cancer drugs [68].
5.2. Antimicrobial activity
5.2.1. Antibacterial and antifungal activity
Previous studies have shown that green propolis extracts inhibit the in vitro growth of
Streptococcus mutans [5,69,8,59]. This microorganism is etiologically related to the formation of
dental caries in humans and animals. Propolis showed efficient antimicrobial activity against
Pseudomonas sp and Staphylococcus aureus [70]. Propolis antimicrobial effect is directly propor‐
tional to its concentration [54]. Propolis ethanolic extracts exhibited significant antimicrobial
activity against many pathogens from the oral cavity, including Porphyromonas gingivalis,
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Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum [(69,24,71], which is the main
microbiota involved in periodontal disease related to plaque. Gram-positive bacteria are more
sensitive than Gram-negative bacteria to propolis extracts [72]. So far, no data is available to
answer this observation. Gram-negative bacteria have a cell wall chemically more complex
and a higher fat content, which may explain the higher resistance [73,74]. Antibacterial activity
of green propolis derives mainly of flavonoids, aromatic acids, esters present in resins,
galangin, pinostrobin, and pinocembrin which have been known as the more effective agents
against bacteria. Ferulic acid and caffeic acid also contribute to the bactericidal action of
propolis [5]. A simple analogy can not be made to the mode of action of classic antibiotics.
There are no reports considering the resistance to bacterial constituents of propolis, and these
properties may influence the success of antibiotic therapy in the oral cavity [63]. The solvent
used for propolis extraction (ethanol, chloroform, methanol, propylene glycol, for example)
can influence its antimicrobial activity. In fact, oily preparations have high antimicrobial
activity, while solutions of glycerin showed little inhibition of Gram-positive and ethanolic
solutions and propylene glycol showed good activity against yeasts [74]. Several studies have
reported synergistic activity of propolis associated with various antibiotics, including activity
against strains resistant to benzylpenicillin, tetracycline and erythromycin. These studies
concluded that propolis has significant synergistic action, which may constitute an alternative
therapy for microbial resistance, but dependent on its composition [75,9,76]. Propolis has also
shown fungistatic and fungicidal activity in vitro against yeasts identified as cause of onycho‐
mycosis [35]. Although propolis is not widely used in conventional health care, is recom‐
mended for use as home remedies in the treatment of oral candidosis, denture stomatitis and
skin lesions by numerous books and articles in the popular press [77,78]. Although some
studies have focused on showing the antifungal activity of propolis extract, few have shown
their effects on morphology and structure of Candida albicans [79,80]. Combinations of some
drugs, antimycotic with propolis (10%) increase their activity against the yeast Candida
albicans. The greatest synergistic effect against various strains were obtained when propolis is
combined with other antifungal agents [5]. Siqueira et al.[81] demonstrated the antifungal
activity of aqueous and alcoholic extracts of the green propolis and the alcoholic extract of red
propolis was observed against Trichophyton rubrum, Trichophyton tonsurans and Trichophyton
mentagrohytes samples, using as controls itraconazole and terbinafine. The data obtained
showed that the green propolis alcoholic extract's antifungal activity was from 64 to 1024 µg/
mL. The antifungal activity of red propolis alcoholic extract was more efficient than the green
propolis alcoholic extract for all three species studied. The antifungal potential of the alcoholic
extracts of green and red propolis demonstrated suggest an applicable potential as an alter‐
native treatment for dermatophytosis caused by these species [82, 81]. On the other hand the
diterpenes: 14,15-dinor-13-oxo-8(17)-labden-19-oic acid and a mixture of labda-8(17),13E-
dien-19-carboxy-15-yl oleate and palmitate as well as the triterpenes, 3,4-seco-cycloart-12-
hydroxy-4(28),24-dien-3-oic acid and cycloart-3,7-dihydroxy-24-en-28-oic acid were isolated
from Cretan propolis. All isolated compounds were tested for antimicrobial activity against
some Gram-positive and Gram-negative bacteria as well as against some human pathogenic
fungi showing a broad spectrum of antimicrobial activity [83]. Concerning the antimicrobial
activity of propolis phenols, Candida albicans was the most resistant and Staphylococcus aureus
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the most sensitive from Portugal, Braganca and Beja`s propolis. The reference microorganisms
were more sensitive than the ones isolated from biological fluids [84]. Tables 4, 5, 6, and 7 show
results from in vitro antimicrobial activity of ethanolic extract and gel containing Brazilian
green propolis. Imaging studies with electron microscopy suggest the rupture of the cell wall
of Candida albicans as one of the mechanisms of action of Brazilian green propolis (Figure 1) [78].
Figure 1. Micrographs showing C. albicans treated for 24h with subinhibitory concentrations of Brazilian Green Propo‐
lis extract (BGP). Scanning electron micrographs: Treated (panels A, B, and C) and untreated (panel D). A and B: cell
wall detachment. C: cell agglomeration. Mello et al. [78].
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Microorganisms MIC (ìg/mL) MBC (ìg/mL) Inhibition zones (M±SD
=mm)
C. albicans 20-50 100-300 16.3±0.52
C. tropicalis 20-50 100-300 12.3±0.08
C. glabrata 20-50 100-300 15.6±0.50
C. krusei 20-50 100-400 28.3±0.15
C. parapsilosis 20-50 100-400 18.6±0.08
C. guilliermondii 20-50 100-400 12.6±0.57
S. mutans 25-50 200-400 18.3±1.15
S. sobrinus 25-50 200-400 28.6±0.57
P. intermedia 20-50 200-400 17.5±2.50
T. forsythensis 30-60 300- 500 14.0±0.00
B. fragilis 25-50 300-500 15.3±1.15
S. aureus 25-50 200-400 16.3±2.08
P. gingivalis 30-50 200-400 14.0±0.00
F. nucleatum 30-60 200-400 15.2±0.26
F. necrophorum 30-60 200-400 17.3±0.57
A. actinomycetemcomitans 30-60 200-400 14.6±0.57
Table 4. Minimum Inhibitory Concentration (MIC); Minimum Bactericidal Concentration (MBC), Means and Standard
Deviation (M±SD) of diameter inhibition zones obtained in agar diffusion test using Brazilian Green Propolis Extract
(BGP) against Candida spp., Gram positive and Gram negative oral pathogenic bacteria. (Tests in triplicate).Paula et al.
[59]
Microorganisms Propolis MIC
(ìg/ml)
Nystatin MIC
(ìg/ml)
Chlorexidine
MIC (ìg/ml)
Tetracycline
MIC (ìg/ml)
C. albicans 14.00 16.00 _ _
C. tropicalis 14.00 16.00 _ _
S. mutans 28.00 _ 8.00 1.00
S. aureus 14.00 _ 32.00 4.00
A. israelii 1.75 _ 32.00 4.00
E. faecalis 7.00 _ - 16.00 2.00
A. actnomycetemcomitans 3.50 _ 8.00 1.00
Table 5. Minimum Inhibitory Concentration (MIC) of propolis ethanolic extract and control obtained for each strain
tested. Tests in quadruplicates. (Paula et al.) [59].
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Propolis
ointment %
Tetracycline
1%
Bacteria
48 hs
activity
7 days
activity
48h 7days
5% 10% 15% 20% 5% 10% 15% 20%
S. mutans 13.33±3.09 19.00±2.00 19.66±2.08 23.33±1.52 9.66±1.52 15.66±2.58 14.33±2.08 18.33±1.52 14.33±0.57 9.33±1.52
S. aureus 13.00±1.00 17.66±2.08 18.66±2.08 21.66±0.57 9.66±0.57 12.33±1.15 14.00±1.00 15.00±2.00 18.33±2.51 11.00±1.53
A. israelii 12.00±1.00 14.66±2.08 15.00±2.08 21.66±2.51 7.33±1.15 9.66±2.08 11.66±2.08 13.66±1.52 14.00±1.73 10.00±1.00
E. faecalis 14.66±1.15 18.33±0.57 21.00±1.00 24.00±1.00 9.66±0.57 11.00±1.00 12.66±0.57 15.00±1.00 9.66±2.08 7.66±1.15
A.a.14.33±1.52 18.00±2.00 21.66±2.08 25.33±2.08 8.66±2.51 11.00±2.00 14.33±1.52 13.66±1.52 18.00±2.00 12.00±1.00
Table 6. Susceptibility of oral bacteria to Brazilian propolis adhesive formulation. Inhibition zones values in mm (M
±SD; n=3). Negative control was inactive..A.a. = A. actinomycetemcomitans (Santos et al.) [71]
Fungi
Propolis
ointment %
Nystatin 5%
48 h activity 7 day activity 48 h 7day
5% 10% 15% 20% 5% 10% 15% 20%
C. albicans 16.33±1.52 21.66±1.57 23.00±1.00 26.00±1.00 12.33±1.52 17.00±1.00 16.66±1.52 20.66±0.57 12.00±2.00 8.66±1.52
C. tropicalis 16.66±2.51 24.33±2.03 23.00±2.00 26.00±2.00 13.33±2.08 19.33±0.57 17.66±0.57 19.00±1.00 14.66±1.52 10.66±1.52
Table 7. Susceptibility of Candida species to Brazilian propolis adhesive formulation. Inhibition zones values in mm (M
±SD; n=3). Negative control was inactive. (Santos et al.) [71]
5.2.2. Antiviral activity
There are many reports on the antiviral activity of propolis. In a study performed in Ukraine
compared the efficacy of ointment with propolis Canadian ointments acyclovir and placebo
(vehicle) in treating subjects with type 2 Herpes applicant. The preparation of propolis
containing flavonoids found to be more effective than the other two in wound healing and
reduction of local symptoms [98]. The cytotoxic and antiherpetic effect of propolis extracts
against HSV-2 was analysed in cell culture, and revealed a moderate cytotoxicity on RC-37
cells. However both propolis extracts exhibited high anti-herpetic activity when viruses were
pretreated with these drugs prior to infection. Selectivity indices were determined at 80 and
42.5µg/mL for the aqueous and ethanolic extract, respectively, thus propolis extracts might be
suitable for topical therapy in recurrent herpetic infection [99]. Huleihel & Isanu [100] reported
potent antiviral activity of propolis against Herpes simplex-1 infection in vitro and in vivo. They
suggested that the propolis can prevent absorption of the virus within the host cells and
interfere with viral replication cycle. In vitro studies suggest that the green propolis has potent
antiviral activity against variants X4 and R5 HIV-1. Similar activity was observed with CD4 +
lymphocytes in operation, at least in part, as an inhibitor of viral entry [101,35]. Also, the
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antiviral activity of components of propolis, such as esters of cinnamic acids replacements was
studied in vitro [5, 9, 102]. The antiviral effect of propolis extracts and selected constituents,
e.g. caffeic acid, p-coumaric acid, benzoic acid, galangin, pinocembrin and chrysin against
herpes simplex virus type 1 (HSV-1) was analysed in cell culture by Schnitzler et al.[103]. The
50% inhibitory concentration IC50 of hydro ethanolic propolis extracts for HSV-1 plaque
formation was determined at 0.0004% and 0.000035%, respectively. Both propolis extracts
exhibited high levels of antiviral activity against HSV-1 in viral suspension tests, plaque
formation was significantly reduced by >98%. Both propolis extracts exhibited high anti-HSV-1
activity when the viruses were pretreated with these drugs prior to infection. Among the
analysed compounds, only galangin and chrysin displayed some antiviral activity. However,
the extracts containing many different components exhibited significantly higher antiherpetic
effects as well as higher selectivity indices than single isolated constituents. Propolis extracts
might be suitable for topical application against herpes infection [104]
5.3. Antioxidative activity
The antioxidative activity deserves special interest because propolis could be topically applied
successfully to prevent and treat skin damaged [85, 86, 87]. Phenolic compounds found in high
concentrations in Brazilian green propolis, including Artepillin C, have a wide range of
biological properties including the ability to act as an anti-oxidizing free radicals and nitric
oxide radicals and also the ability to interfere with the inflammatory response through
inhibition of iNOS and COX-2 activities [88]. Although studies of propolis ethanol extracts are
very common, it is reported that the aqueous extract has good antioxidant activity, associated
with high content of phenolic compounds [89,90,91, 92]. Some studies have indicated propolis
inhibiting superoxide anion formation, which is produced during autoxidation of â-mercap‐
toethanol [93,2]. The antioxidative activity of propolis and its main phenolic compounds,
caffeic acid, p-coumaric acid, ferulic acid, and caffeic acid phenethyl ester, were investigated
in yeast Saccharomyces cerevisiae. Yeast cells showed decreased intracellular oxidation, with no
significant differences seen for the individual phenolic compounds. Ethanol Extract Propolis
(EEP) antioxidative activity was also investigated at the mitochondrial proteome level and
changes in the levels of antioxidative proteins and proteins involved in ATP synthesis were
seen [94]. Brazilian green propolis is derived of B. dracunculifolia and protective effects of B.
dracunculifolia glycolic extract against oxidative stress in isolated rat liver mitochondria (RLM)
were investigated by Guimaraes et al.[95]. So, B. dracunculifolia exhibit potent antioxidant
activity protecting liver mitochondria against oxidative damage and such action probably
contribute to the antioxidant and hepatoprotective effects of green propolis [95]-. CAPE are
involved with the renal damage protection induced by Cd (II) owing to its antioxidant capacity
and anti-inflammatory effect [96]. Preadministration of Brazilian Propolis Ethanol Extract (50
or 100 mg/kg) to the stressed rats protected against the hepatic damage and attenuated the
increased hepatic lipid peroxide and NO(x) contents and myeloperoxidase activity and the
decreased hepatic non-protein SH and ascorbic acid contents and superoxide dismutase
activity, possibly through its antioxidant and antiinflammatory properties [97].
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5.4. Antitumoral activity
Several researchers reported the antitumoral property of propolis in vitro and in vivo [105,106,
30, 68]. Propolis isolated components showed antiproliferative activity in tumor cells [6].
Artepilin C, the major component of Brazilian green propolis, has antiangiogenic activity.
Propolis may suppress tumor growth in vivo, but these mechanism effects is not completely
understood [107, 39, 60]. Propolis shows antitumor properties, and its anticarcinogenic and
antimutagenic potential is promising, but the mechanisms involved in chemoprevention are
still unclear [108]. On other hand, CAPE and chrysin may be useful as potential chemothera‐
peutic or chemopreventive anticancer drugs [42]. However, the human aldo-keto reductase
(AKR) 1C3, also known as type-5 17â-hydroxysteroid dehydrogenase and prostaglandin F
synthase, has been suggested as a therapeutic target in the treatment of prostate and breast
cancers was inhibited by Brazilian propolis-derived cinnamic acid derivatives that show
potential antitumor activity, and it was found that baccharin a potent competitive inhibitor
(K(i) 56 nM) with high selectivity [109]. There are currently several authors studied the
antitumor activity of propolis, especially its components. Some initial studies are, however,
some authors already have in-depth evaluation of about the propolis activity onto various
animal or human types of tumor cell lines [110-115].
5.5. Immunomodulatory activity
The immunomodulatory activity of propolis is one of the most studied areas in conjunction
with its anti-inflammatory property [116-120]. The immunomodulatory action of propolis
seems to be limited to macrophages, with no influence on the proliferation of lymphocytes
[121]. The inhibitory effect of green propolis (5-100µg/mL) on splenocyte proliferation was
observed in vitro [122], and previous studies demonstrated that flavonoids have an immuno‐
suppressive effect in lymphoproliferative response [123-125]. Since, propolis contains flavo‐
noids, that may explain the reported effect [6,10]. Another explanation for the inhibitory effect
on lymphocyte proliferation from the observation that both CAPE has inhibitory effects on
transcription of nuclear factor-êB (NF-êB) (p65) and nuclear factor of activated T-cells (NFAT).
Consequently, CAPE inhibited IL-2 gene transcription, IL-2R (CD25) expression and prolifer‐
ation of human T cells, providing new insights into the molecular mechanisms involved in
inflammatory and immunomodulatory activities of this natural component [6]. Green propolis
exhibited immuno-stimulatory and immunomodulatory effects on CD4/CD8T cells and on
macrophages in vitro and in vivo mice [126]. Propolis administration to melanoma-bearing mice
submitted to stress stimulated IL-2 expression, as well as Th1 cytokine (IL-2 and IFN-ã)
production, indicating the activation of antitumor cell-mediated immunity. Also, propolis
stimulated IL-10 expression and production, which may be related to immunoregulatory
effects indicating its antitumor action in vivo [127]. On other hand, Orsatti and Sforcin [128]
demonstrated the propolis immunomodulatory action in chronically stressed mice, upregu‐
lating TLR-2 and TLR-4 mRNA expression, contributing to the recognition of microorganisms
and favoring the initial steps of the immune response during stress. A new line of research
involving propolis is the possible application as a vaccination adjuvant, although most
commercial vaccines use aluminum salts to this end. A sample of green Brazilian propolis was
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tested, together with other adjuvant compounds, to immunize mice against inactivated swine
herpes virus (SuHV-1). When administered together with aluminum hydroxide, the propolis
extract increased both cellular and humoral responses [103].
6. Toxicity
It must be emphasized that propolis has the advantage of being a natural product, with a
higher molecular diversity. It has many therapeutic substances compatible with the me‐
tabolism of mammals in general, which reduces the possibility of causing adverse reac‐
tions to oral tissue as compared to industrial products tested [13]. The aqueous and
alcoholic extracts of propolis do not cause irritation to the tissues [17] and are considered
relatively toxic [7]. Experimental mouthwash solutions containing propolis showed no sig‐
nificant inhibitory activity of microorganisms as effective as chlorhexidine, but found low‐
er cytotoxicity on human gingival fibroblasts; propolis is relatively non-toxic and studies
have exhibited a no-effect level in a mice study of 1400 mg/kg weight/day leading the au‐
thors to propose that a safe dose in humans would be 1.4 mg/kg weight/day, or approxi‐
mately 70 mg/day [63]. On other hand, Pereira et al. [29] demonstrated high effectiveness
of mouthwash containing propolis in control of dental plaque and gingivitis in humans
and not observed no toxic or side effects in the administration of the rinse during 90
days. Propolis is considered safe in small doses. Therefore, adverse effects are common at
doses above 15g/day. The most commonly experienced adverse effects are allergic reac‐
tions, as well as irritation of the skin or mucous membranes [129]. Caution should be
used in the treatment of individuals with asthma and eczema and nettle rash [2].
7. Standardization
A universal chemical standardization of propolis would be impossible. Therefore, a detailed
investigation of its composition, botanical origin and biological properties is significant [6]. It
was postulated that different propolis may have different chemical and pharmaceutical
properties. In this sense, standardization of propolis is required. Most studies on the chemistry
of propolis include those directed to the European propolis composed of Populus sp. These
studies have been conducted by paired with Gas Chromatography Mass Spectrometry (GC-
MS). Therefore, due to the lower reproducibility of these methods, the use of High- Perform‐
ance Liquid Chromatography (HPLC) is currently recommended [22,130,131]. An alternative
method, using electro-spray, was recently tested to determine the patterns and content of
polyphenolic components of propolis [132]. Nuclear magnetic resonance is one of the best
detection methods because it recognizes components sensitive or insensitive to Ultraviolet
Light (UL) [133,134]. Standardization can prevent product adulteration. Therefore, the
methods used to extract components of propolis require adequate standardization [22, 87,135].
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8. Oral clinical studies
Several clinical studies have demonstrated propolis efficacy in clinical trials, but the majority
of studies involve topical application [20, 136-138]. The great diversity and the complexicity
of chemical components makes difficult to standardize and to research the mechanisms of
action. It is known the propolis anti-inflammatory, anti-microbial, analgesic, antioxidant, and
antitumorproperties. Recently, some authors have demonstrated the properties of some
components, however, one can not consider when using propolis but as a whole. The antimi‐
crobial activity, for example, may be effective when considering the synergism between the
components. Moreover, there was always the concern of several authors to develop oral
mouthwashes- based propolis to control oral microbiota [138-140]. Koo et al.[141] demon‐
strated the effect of a mouthrinse containing selected propolis on 3-day dental plaque accu‐
mulation and polysaccharide formation and observed the Dental Plaque Index(PI) for the
experimental group was 0.78 (0.17), significantly less than for the placebo group, 1.41 (0.14).
On other hand, the experimental mouthrinse reduced the PI concentration in dental plaque by
61.7% compared to placebo (p < 0.05). The clinical efficacy of an alcohol-free mouthwash
containing 5.0% (W/V) Brazilian green propolis (MGP 5%) for the control of plaque and
gingivitis were demonstrated by Pereira et al.[29] (Tables 8, 9, 10, and 11). Twenty five subjects,
men and women aging between 18 and 60 years old (35 ± 9), were included in a clinical trial`s
phase II study of the patients who had a minimum of 20 sound natural teeth, a mean plaque
index of at least 1.5 (PI), and a mean gingival index (GI) of at least 1.0. They were instructed
to rinse with 10mL of mouthwash test for 1 minute, immediately after brushing in the morning
and at night. After 45 and 90 days using mouthwash, the results showed a significant reduction
in plaque and in gingival index when compared to samples obtained in baseline. These
reductions were at 24% and 40%, respectively (P <0.5). There were no important side effects in
soft and hard tissues of the mouth.
Baseline 45 days 90 days Reduction %
MGP5% N=22
1.17 (0.20)
N=22
0.64 (0.24)
N=21
0.70 (0.18)
Baseline- 45 days
45*
Baseline- 90 days
40* 45 days – 90 days
Table 8. Mean scores of Gingival Index (DP) and percent reduction between periods (Pereira et al., 2011) [29].
Friedman test (ANOVA) P <.05.
Baseline 45 days 90 days Reduction-%
MGP5% n = 22
0.30 (0.17)
n = 22
0.08 (0.06)
n = 21
0.07 (0.03)
Baseline–45
days
73*
Baseline–90 days
77*
45 days–90 days
13 (ns)**
Table 9. Mean scores of Severity Gengival Index (DP) and percent reduction between periods (Pereira et al., 2011)
[29]. *Friedman test (ANOVA) P <.05. ∗∗Not significant.
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Baseline 45 days 90 days Reduction-%
MGP5% n = 22
2.39 (0.69)
n = 22
1.77 (0.61)
n = 21
1.82 (0.62)
Baseline–45
days
26*
Baseline–90 days
24*
45 days–90 days∗
______
Table 10. Mean scores of Plaque Index (DP) and percent reduction between periods (Pereira et al., 2011)
[29].Friedman test (ANOVA) P <.05.
Baseline 45 days 90 days Reduction-%
MGP5% n = 22
0.44 (0.19)
n = 22
0.26 (0.14)
n = 21
0.26 (0.15)
Baseline–45 days
41*
Baseline–90 days
41*
45 days–90 days
____
Table 11. Mean scores of Severity Plaque Index (DP) and percent between periods (Pereira et al., 2011) [29].
Friedman test (ANOVA) P <.05.
In this study, the MGP 5% showed evidence of its efficacy in reducing PI and GI. However, it
is necessary to perform a clinical trial, double-blind, randomized to validate such effectiveness
[29]. Regression of 95% gingivitis and suppuration in all the teeth irrigated with Brazilian
Green Propolis gel (BGPg), as well as a pocket depths and all treated patients with the BGPg
showed periodontitis/gingivitis regression. This result suggest that 10% BGPG used could be
used as an adjuvant therapeutic method assigned for the treatment of periodontal disease
(Figure 2) [142]. Ethanol Propolis Extract (EPE) inhibited all the Candida albicans strains
collected from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidia‐
sis. No significant difference was observed between Nystatin and EPE. But significant
differences were observed between EPE and other antifungals. C. albicans showed resistance
to antifungal agents. This fact suggests commercial EPE could be an alternative medicine for
candidosis treatment from HIV-positive patients (Figure 3) [143]. Brazilian commercial ethanol
propolis extract, also formulated to ensure physical and chemical stability, was found to inhibit
oral candidiasis in 12 denture-bearing patients with prosthesis stomatitis candidiasis associa‐
tion is show in Table 12 and Figure 4 [144]. Also, denture stomatitis presents as a chronic disease
in denture-bearing patients, especially under maxillary prosthesis. Despite the existence of a
great number of antifungal agents, treatment failure is observed frequently. So, the clinical
efficacy of a Brazilian propolis gel formulation in patients diagnosed with denture stomatitis
was evaluated. Thirty complete-denture wearers with denture stomatitis were enrolled in this
pilot study. At baseline, clinical evaluation was performed by a single clinician and instructions
for denture hygiene provided. Fifteen patients received Daktarin® (Miconazole gel) and 15
received Brazilian propolis gel. All patients were recommended to apply the product four
times a day during one week. Clinical evaluation was repeated by the same clinician after
treatment. All patients treated with Brazilian propolis gel and Daktarin® had complete clinical
remission of palatal candidiasis edema and erythema. [77]. Noronha [31] found the efficacy of
a Brazilian green propolis mucoadhesive gel (BPGg) in preventing and treating the oral
mucositis and candidiasis in patients harboring malignant tumors and receiving radiotherapy.
All patients who used the gel applied 24 hours before the first radiotherapy session, three times
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a day, during the whole period(six weeks) of radiotherapy, did not develop mucositis and
candidosis over the entire period of radiotherapy.
Figure 2. Periodontitis treatment with mucoadhesive green propolis gel. A) Evidencing of dental plaque with basic
fuchsin. B) Confirmation of insertion loss and presence of periodontal pockets with periodontal probe. C) Applying
mucoadhesive green propolis gel intra-periodontal pocket. D) Clinical aspect of the periodontium after treatment
with gel containing propolis (Cairo do Amaral et al. [142].
The prevalence of candidosis in denture wearers is as well established as its treatment with
antifungal agents (AAs). However, little research has been done regarding the effects of AAs
on denture base surfaces. Then, da Silva et al.[150] evaluate the effects of fluconazole (FLU),
nystatin (NYS) and propolis orabase gel (PRO) on poly (methyl-methacrylate) (PMMA)
surfaces. So, PRO was able to induce changes in PMMA surface properties, such as roughness,
which could be related to microbial adhesion [146]. Recurrent aphthous stomatitis (RAS) is a
common, painful, and ulcerative disorder of the oral cavity of unknown etiology. No cure
exists and medications aim to reduce pain associated with ulcers through topical applications
or reduce outbreak frequency with systemic medications, many having serious side effects.
Propolis is a bee product used in some cultures as treatment for mouth ulcers. A randomized,
double-blind, placebo-controlled study, patients were assigned to take 500 mg of propolis or
a placebo capsule daily. Subjects reported a baseline ulcer frequency and were contacted
biweekly to record recurrences. Data were analyzed to determine if subjects had a decrease of
50% in outbreak frequency. The data indicated a statistically significant reduction of outbreaks
in the propolis group (Fisher's exact test, one sided, p = 0.04). Patients in the propolis group
also self-reported a significant improvement in their quality of life (p = 0.03). This study has
shown propolis to be effective in decreasing the number of recurrences and improve the quality
of life in patients who suffer from RAS [145].
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Figure 3. Inhibition zones of in vitro culture of Candida albicans collected from HIV-positive patients exposed to Etha‐
nol Propolis Extract (EPE= P), and antifungal agents: CL= clotrimazole; FL= fluconazole; EC= Econazole; NY =Nystatin;
AL= Alcohol; DW= Destiled water. (Martins et al., 2002) [143].
Figure 4. Clinical aspects of oral candidosis in patients with Total Removable Dental Prothesis (TRDP). A) Before prop‐
olis use. B) After propolis use. Source: Prof. Vagner Santos archives (2005) [146].
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Patient Age
(years) Race Gender Prosthesis Local lesions Antifungal
agent Result
ISS Hard 29 B F TRDP palate/soft palate Nys +
SVCL 34 W F TRDP Hard palate Nys +
AFF 36 W M TRDP Hard palate Nys +
GMR 37 W M TRDP Hard / soft palate Nys ++
MIC 39 B F TRDP Hard palate NYS +
AFS 71 B F TRDP Hard palate Nys ++
EGSM 29 W F TRDP Hard /soft palate EPE +
TMS 31 B F TRDP Hard palate EPE ++
LMC 33 W M TRDP Hard palate EPE +
HL 38 W M TRDP/PRDP Hard palate/ alveolar
mucosa EPE +
SFS 39 W F TRDP Hard /soft palate EPE ++
MCTS 43 W M TRDP/PRDP Hard palate/ alveolar
mucosa EPE +
MJNM 46 W F TRDP Hard palate EPE ++
46 B F TRDP Hard palate EPE +
HBS 48 B M TRDP Hard palate EPE +
JJAF 50 W F TRDP Hard palate EPE +
GRA 56 W F TRDP Hard palate EPE ++
NMBA 63 W F TRDP Hard palate EPE ++
Table 12. Clinical aspects of patients with oral candidiasis from Clinic of Semiology and Pathology of Dentistry School
UFMG participating in this study and Results of in vivo patients treatment of oral candidiasis with 20% Brazilian green
ethanol propolis extract (EPE) and Nystatin (Nys). Use posology: 4 time/day for 7 days, topic application in local lesion
and prosthesis surface F, female; M, male; TRDP, total removable dental prosthesis; PRDP, partial removable dental
prosthesis; B, black; W, white. (Santos et al., 2005) [146]
9. Future perspectives
The potential pharmacological activity investigation of natural products, especially antimi‐
crobial activity, has attracted the attention of several researchers. Increase of bacterial resist‐
ance to traditional antimicrobial agents and side effects are often seen [147, 28]. Many
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mouthwashes with alcohol are used as adjuvants in the control of dental plaque and gingivitis,
but undesirable side effects are observed, despite its efficacy. This stimulates the research of
alternative products, such as the use of toothpastes and mouthwashes based on natural
products, because there is the need for prevention and treatment options that are safe, effective
and economical. Mouthwash based on herbal extracts and propolis are for sale in the Brazilian
and world market, without, however, have undergone clinical studies proving their effective‐
ness and documenting possible undesirable side effects. Previous studies have demonstrated
the efficacy of propolis extracts as an antimicrobial agent useful for dental caries and perio‐
dontal pathogens microorganisms in in vitro studies [24,78,59,148,149]. Propolis standardiza‐
tion is necessary and several authors from different countries are involved in the study of
pharmacological activity and mechanism of action of various types of propolis. The separation
of organic compounds and their mechanism of action on cells may lead to new products that
can be important in controlling tumor growth, and infection control. However one should not
forget that the effect of synergism observed in raw propolis is responsible for its excellent
antimicrobial activity making it a unique product against bacterial and fungal resistance.
Moreover, pre-clinical and clinical phase I, II, III studies are necesssary in order to better
determine the effect on patients and safety. Several components of propolis have shown
efficacy in the growth inhibition of in vitro tumor cells and in vivo tumors. This may be the way
to the discovery of drugs against cancer, however, the clinical confirmations should be
prioritized. The diversity of pharmacological properties of propolis may also be extended to
studies against autoimmune diseases in order to ameliorate the clinical evolution. Also, studies
against systemic diseases that affect largely population world as is the case of diabetes and
hypertension. But for that attention should turn to as separation of compounds that can be a
great gain for treatment of these diseases.
(a)
(b)
Figure 5. (a) Physical aspect of Brazilian green crude propolis. (b) Plant caracteristic of Baccharis dracunculifolia. (Prof.
Vagner Santos archives, 2012).
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Propolis component Pharmacological properties Author/year
Green Propolis extract Apoptosis and cell propliferation Giertsen et al, 2011 [153]
Moronic acid Epstein-Barr virus suppresion Chang et al., 2010 [154]
Polyphenols Neurological diseases Farooqui and Farooqui, 2012 [15]
Red propolis extract Adipocyte differentiation Iio et al., 2010 [155]
Caffeic acid phenethyl ester
Cardanol, cardol
Antitumoral / anticancer,
citotoxicity
Chuu et al., 2012 [156]
Sawaya et al., 2011 [39]
Chan et al., 2012 [152]
Watanabe et al., 2011 [159]
Teerasripreecha et al, 2012 [68]
epicatechin, p-coumaric acid, morin, 3,4-
dimethoxycinnamic acid, naringenin, ferulic
acid, cinnamic acid, pinocembrin, and chrysin ,
3-prenyl-4-hydroxycinnamic acid
Antioxidant Guimaraes et al., 2012 [95]
Guo et al., 2011 [87]
Sawaya et al, 2011 [39]
3-prenyl-4-hydroxycunnamic acid, 2,2-
dimethyl-6-carboxyethenyl,2H-1-benzopyran;
3,5-diprenyl-4-hydroxycinnamic acid derivative
4 (DHCA4) 2,2-dimethyl-6-
carboxyethenyl-2H-1-benzopyran (DCBEN
Antiparasitic Trypanosoma cruzi;
Leishmania amazonensis
Sawaya et al., 2011 [39]
Salomao et al., 2008 [160]
Salaomao et al., 2011 [161]
Green, red and brown propolis extracts;
Artepillin C; Crysin
Anti-inflamatory Marcucci et al., 2000 [11]
Ha et al., 2010 [158]
Sawaya et al., 2011 [39]
Moura et al., 2011 [57]
Orsatti et al., 2012 [128]
Green, Red, Brown propolis extract; p-coumaric
acid (PCUM), 3-(4-hydroxy-3-(oxo-butenyl)-
phenylacrylic acid (DHCA1); Caffeic acid,
caffeoylquinic acid, diterpenic acids, flavonoids
antimicrobial Martins et al., 2002 [143]
Paula et al., 2006 [59];
Santos et al., 2007 [71]
Dias et al., 2012 [162];
Mattigatti et al., 2012 [163] Sawaya
et al., 2011 [39]
Choudhari et al., 2012 [157]
Table 13. Recent advances in propolis components studies.
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
155
(b)
Figure 6. (a) Physical aspect of Brazilian red propolis. (Prof. Vagner Santos archives, 2012) (b) Dalbergia ecastophylum
plant aspect. http://www.google.com.br/imgres?q=Dalbergia+ecastophyllum&num=10&hl=pt
BR&biw=1280&bih=673&tbm= isch&tbnid=WIUAFEd2jCOSxM:&imgrefurl=http://meliponariojandaira.blogspot.com/
2011/02/abelhas-indigenas-sem-ferrao.
Acknowledgements
Research Foundation of Minas Gerais State (FAPEMIG), National Council of Scientific and
Tecnologic Development (CNPq) for financial support in all of our research group and also
for supporting the publication of this chapter. Special thanks to Gustavo Araujo and Rafael
Tomaz.
Author details
Vagner Rodrigues Santos
Address all correspondence to: vegneer2003@yahoo.com.br
Universidade Federal de Minas Gerais, Faculty of Dentistry, Department of Clinical, Pathol‐
ogy and Surgery, Laboratory of Microbiology and Biomaterials, Brazil
Alternative Medicine
156
References
[1] Souza BM, Palma MS. Peptides from Hymenoptera venoms. In: Lima M.H. (ed). Animal
Toxins: State of Art - Perspectives in Health and Biotechnology. EditoraUFMG. 2009.p
345-367.
[2] Castaldo S, Capasso F. Propolis, an old remedy used in modern medicine. Fitoterapia.
2002; 73(Suppl 1) S1- S6.
[3] Salatino, A; Teixeira, E.W.; Negri, G.; Message, D. Origin and Chemical Variation of
Brazilian Própolis. Evidence-Based Complementary and Alternative Medicine 2005;
2(1) 33–38.
[4] Bankova V. Recent trends and important developments in propolis research. Evidence-
Based Complementary Alternative Medicine 2005; 2(1) 29-32.(a)
[5] Marcucci MC. Propolis: chemical composition, biological properties and therapeutic
activity. Apidologie 1995; 26(2) 83–99, 1995.
[6] Sforcin JM. Propolis and the immune system: a review. Journal Ethnopharmacology
2007; 113(1) 1-14.
[7] Burdock GA. Review of the biological properties and toxicity of bee propolis (propolis).
Food and Chemical Toxicology 1998; 36(4) 347–363.
[8] Boyanova L, Kolarov R, Gergova G, Mitov I. In vitro activity of Bulgarian propolis
against 94 clinical isolates of anaerobic bacteria. Anaerobe 2006; 12(4) 173-77.
[9] Fernandes FF, Dias ALT, Ramos CL, Ikegak M, Siqueira AM, Franco MC The “in vitro”
antifungal activity evaluation of propolis G12 ethanol extract on Cryptococcus neofor‐
mans. Revista do Instituto de Medicina Tropical de Sao. Paulo 2007; 49(2) 93-95.
[10] Piccinelli AL, Lotti C, Campone L, Cuesta-Rubio O, Campo Fernandez M, Rastrelli L
Cuban and Brazilian red propolis: botanical origin and comparative analysis by high-
performance liquid chromatography-photodiode array detection/electrospray ioniza‐
tion tandem mass spectrometry. Journal of Agricultural Food and Chemistry. 2011; 59
(12) 6484-91.
[11] Marcucci, M.C.; Ferreres, F.; Custódio, A. Evaluation of phenolic compounds in
Brazilian própolis from different geographic regions. Z. Naturforsch. 2000; 55 ( 1 ) 76-86.
[12] Bankova, V. Chemical diversity of propolis and the problem of standardization. Journal
of Ethnopharmacology 2005; 100 (1) 114-117. (b)
[13] Simões CC, Araújo DB, Araújo RPC. Estudo in vitro e ex vivo da ação de diferentes
concentrações de extratos de própolis frente aos microrganismos presentes na saliva
de humanos. Brazilian Journal of Pharmacognosy 2008; 18(1) 84-89.
[14] Menezes H. Própolis: uma revisão dos recentes estudos de suas propriedades farma‐
cológicas. Arquivos do Instituto de Biologia 2005; 72(3) 405-411.
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
157
[15] Farooqui T, Farooqui AA. Beneficial effects of propolis on human health and neuro‐
logical diseases. Frontiers in Bioscience (Elite Ed) 2012; 4(1) 779-793.
[16] Aliyazicioglu Y, Demir S, Turan I, Cakiroglu TN, Akalin I, Deger O, Bedir A. Preventive
and protective effects of Turkish propolis on H₂O₂-induced DNA damage in foreskin
fibroblast cell lines. Acta Biological Hungarica. 2011; 62(4) 388-396.
[17] Ghisalberti EL. Propolis: a review. Bee World 1979; 60: 59–84.
[18] Park YK, Alencar SM, Moura FF, Ikegaki FFM. Atividade biológica da própolis. Revista
OESP – Alimentação 1999; 27:46-53.
[19] Geraldini, C.A.C.; Salgado, E.G.C.; Rode, S.M. Ação de diferentes soluções de própolis
na superfície dentinária - avaliação ultra-estrutural. Faculdade de Odontologia Sao Jose
dos Campos 2000; 3(2) 28-32 .
[20] Grégio AMT, Lima AAS, Ribas MO, Barbosa APM, Pereira ACP, Koike F, Repeke CEP.
Efeito da Propolis Appis mellifera sobre o processo de reparo de lesões ulceradas na
mucosa bucal de ratos. Estudos em Biologia 2005; 27: 58.
[21] Manara LRB, Anconi SI, Gromatzky A, Conde MC, Bretz WA. Utilização da própolis
em Odontologia. Revista da Faculdade de Odontologia de Bauru 1999; 7(3-4) 15-20.
[22] Peña RC. Propolis standardization: a chemical and biological review. Ciencias de
Investigacao Agraria 2008; 35: 11-20.
[23] Pereira AS, Seixas FRM, Aquino-Neto FR. Própolis: 100 anos de pesquisa e suas
perspectivas futuras. Quimica Nova 2002; 25(1) 321-326.
[24] Santos FA, Bastos EMA, Rodrigues PH, Uzeda M, Carvalho MAR, Farias LM, Moreira
ESA. Susceptibility of Prevotella intermédia/ Prevotella nigrescens and Porphyromonas
gingivalis to propolis (bee glue) and other antimicrobial agents. Anaerobe 2002; 8(1)
9-15.
[25] Boyanova L, Gergova G, Nikolov R, Derejian S, Lazarova E, Latsarov N, Mitov I,
Krastev Z. Activity of Bulgarian própolis against 94 Helicobacter pylori strains in vitro
by agar-well diffusion, agar dilution and disc diffusion methods. Journal Medical
Microbiology 2005; 54( pt5) 481-483.
[26] Auricchio MT, Bugno A, Almodóvar AAB, Pereira TC. Avaliação da atividade antimi‐
crobiana de preparações de própolis comercializadas na cidade de São Paulo. Revista
do Instituto Adolfo Lutz 2007; 65(2) 209-212.
[27] Parker JF; Luz MMS. Método para avaliação e pesquisa da atividade antimicrobiana
de produtos de origem natural. Revista Brasileira de Farmacognosia 2007; 17(1) 102-107.
[28] Libério SA, Pereira AL, Araújo MJ, Dutra RP, Nascimento FR, Monteiro-Neto V, Ribeiro
MN, Gonçalves AG, Guerra RN. The potential use of propolis as a cariostatic agent and
its actions on mutans group streptococci. Journal of Ethnopharmacology 2009; 125(1):
1-9.
Alternative Medicine
158
[29] Pereira EM, da Silva JL, Silva FF, De Luca MP, Ferreira EF, Lorentz TC, Santos VR.
Clinical Evidence of the Efficacy of a Mouthwash Containing Propolis for the Control
of Plaque and Gingivitis: A Phase II Study. Evidence- Based Complementary and
Alternative Medicine 2011; 2011:750249. Epub 2011 Mar 31. PMID: 21584253 [PubMed]
[30] Banskota AH, Tezuka YY, Kadota S. Recent progress in pharmacological research of
propolis. Phytoterapy Research 2001; 15(7) 561-571.
[31] Noronha VRAS. Evidencias preliminares da eficácia de gel contendo propolis na
prevenção e tratamento de mucosite e candidose bucais em pacientes submetidos a
radioterapia em região de cabeça e pescoço. Thesis. Minas Gerais Federal University,
2011.
[32] Park YK, Alencar SM, Aguiar CL. Botanical origin and chemical composition of
Brazilian propolis. Journal of Agricultural and Food Chemistry 2002; 50 (9) 2502-2506.
[33] Miguel MG, Antunes MD. Is propolis safe as an alternative medicine? Journal of
Pharmacy and Bioallied Sciences 2011; 3(4) 479-495.
[34] Park YK, Paredes-Guzman JF, Aguiar CL, Alencar SM, Fujiwara FY. Chemical constit‐
uents in Baccharis dracunculifolia as the main botanical origin of southeastern Brazilian
propolis. Journal Agricultural Food Chemistry 2004; 52 (1) 100-1103.
[35] Lustosa SR, Galindo AB, Nunes LCC, Randau KP, Rolim Neto PJ. Própolis: atualizações
sobre a química e a farmacologia. Brazilian Journal of Pharmacognosy 2008; 18: 447-454.
[36] Silva BB, Rosalen PL, Cury JA, Ikegaki M, Souza VC, Esteves A, Alencar SM. Chemical
composition and botanical origin of red própolis, a new type of Brazilian propolis.
Evidence-Based Complementary and Alternative Medicine 2008; 5(3) 313-316.
[37] Park YK, Ikegaki M, Alencar SM, Moura FF. Evaluation of Brazilian propolis by both
physicochemical methods and biological activity. Honey Bee Science 2000; 21(2): 85-90.
[38] Ahn MR, Kunimasa K, Ohta T, Kumazawa S, Kamihira M, Kaji K, Uto Y, Hori H,
Nagasawa H, Nakayama T. Suppression of tumor-induced angiogenesis by brazilian
propolis: major component artepilin C inhibits in vitro tube formation and endothelial
cell proliferation. Cancer Letters 2007; 252(2) 235-243.
[39] Sawaya AC, Barbosa da Silva Cunha I, Marcucci MC Analytical methods applied to
diverse types of Brazilian propolis. Chemistry Central Journal 2011, 5(1) 27.
[40] Fischer G, Cleff MB, Dummer LA, Paulino N, Paulino AS, Vilela CO, Campos FS, Storch
T, Vargas GD, Hübner SO, Vidor T. Adjuvant effect of green propolis on humoral
immune response of bovines immunized with bovine herpesvirus type 5. Veterinary
Immunology and Immunopathology 2007; 116( 1 ) 79–84.
[41] Alencar SM, Oldoni TL, Castro ML, Cabral IS, Costa-Neto CM, Cury JA, Rosalen PL,
Ikegaki M. Chemical composition and biological activity of a new type of Brazilian
propolis: red propolis. Journal of Ethnopharmacology 2007; 113(2) 278-83.
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
159
[42] Sawicka D, Car H, Borawska MH, Nikliński. The anticancer activity of propolis. Folia
Histochemica Cytobiologica 2012; 50(1) 25-37.
[43] Maciejewicz W. Isolation of flavonoid aglycones from propolis by a column chroma‐
tography method and their identification by GC-MS and TLC methods. Journal of
Liquid Chromatography and Related Technolology 2001; 24 (1) 1171-1179.
[44] Kumazawa S, Goto H, Hamasaka T, Fukumoto S, Fujimoto T, Nakayama T. A new
prenylated flavonoid from propolis collected in Okinawa, Japan. Biosciences Biotech‐
nology and Biochemistry 2004; 68(1) 260-262.
[45] Ozkul Y, Silici S, Eroğlu E. The anticarcinogenic effect of propolis in human lympho‐
cytes culture. Phytomedicine. 2005; 12(10) 742-747.
[46] Eremia N, Dabija T. The content micro- and macroelements in propolis. Bulletin
USAMV-CN 2007; 63–64.
[47] Machado GM, Leon LL, De Castro SL. Activity of Brazilian and Bulgarian propolis
against different species of Leishmania. Memorial do Instituto Oswaldo Cruz 2007;
102(1) 74–77.
[48] Vandar-Unlu G, Silici S, Unlu M. Composition and in vitro antimicrobial activity of
Populus buds and poplar-type propolis. World Journal of Microbiology and Biotech‐
nology 2008; 24 (1) 1011–1017.
[49] Wang HQ, Sun XB, Xu YX, Zhao H, Zhu QY, Zhu CQ. Astaxanthin upregulates heme
oxygenase-1 expression through ERK 1/2 pathway and its protective effect against beta-
amyloid-induced cytotoxicity in SH-SY5Y cells. Brain Research 2010; 1360(1) 159–167.
[50] Veronese R. Própolis na clínica e cirúrgia odontológica. Revisão. Disponível em: http://
www.brazilianapis.com/public/propolisnaclinicarespiratoriaeotorrinolaringolo‐
gia.pdf. Acesso em 13 de julho de 2012.
[51] Cizmárik J, Matel I. Examination of the chemical composition of propolis I. Isolation
and identification of the 3,4-dihydroxycinnamic acid (caffeic acid) from propolis.
Experientia. 1970;26(7) 713.
[52] Kadakov, V. P.; Mulearchuk, M. D. Aminoacidos encontrados en el propoleos. Pche‐
lovodstvo 1978; 12: 34.
[53] Endler A L, Oliveira SC, Amorim CA, Carvalho MP, Pileggi M. Teste de Eficácia da
Própolis no Combate a Bactérias Patogênicas das Vias Respiratórias. Publicacao UEPG
Ciencias Biologicas e Saúde 2003; .9(2)17-20.
[54] Awale S, Shrestha SP, Tezuka Y, Ueda JY, Matsushige K, Kadota S. Neoflavonoids and
related constituents from Nepalese propolis and their nitric oxide production inhibi‐
tory activity. Journal of Natural Products 2005; 68(6) 858-864.
[55] Funari, C.S.; Ferro, V.O. Análise de própolis. Ciencias e Tecnologia de Alimentos 2006;
26 (1) 171-178.
Alternative Medicine
160
[56] de Moura SA, Ferreira MA, Andrade SP, Reis ML, Noviello Mde L, Cara DC. Brazilian
green propolis inhibits inflammatory angiogenesis in a murine sponge model. Evi‐
dence-Based Complementary and Alternative Medicine 2011; 2011:182703. Epub 2011
Mar 9.
[57] Kujumgiev A, Tsvetkova I, Serkedjieva Yu, Bankova V, Christov R, Popov S. Antibac‐
terial, antifungal and antiviral activity of propolis of different geographic origin.
Journal of Ethnopharmacology 1999; 64 (3) 235–240.
[58] Paula AMB, Gomes RT, Santiago WK, Dias RS, Cortés ME, Santos VR. Susceptibility of
oral pathogenic bacteria and fungi to brazilian green propolis extract. Pharmacolo‐
gyonline 2006;. 3: 467-473.
[59] Fischer G, Conceição FR, Leite FPL, Dummer LA, Vargas GD, Hübner SO, Dellagostin
OA, Paulino N, Paulino AS, Vidor T: Immunomodulaation produced by green propolis
extract on humoral and cellular responses in mice immunized with SuHV-1. Vaccine
2007; 25 (1) 1250-1256.
[60] Chan GC, Cheung KW, Sze DM. The Immunomodulatory and Anticancer Properties
of Propolis. Clinical Review Allergy Immunology 2012; Jun 17 [Epub ahead of print]
PMID: 22707327 [PubMed - as supplied by publisher]
[61] Ozan F, Sümer Z, Polat ZA, Er K, Ozan U, Deger O. Effect of mouthrinse containing
propolis on oral microorganisms and human gingival fibroblasts. European Journal
Dental 2007; 1(4)195-201.
[62] Tani H, Hasumi K, Tatefuji T, Hashimoto K, Koshino H, Takahashi S. Inhibitory activity
of Brazilian green propolis components and their derivatives on the release of cys-
leukotrienes. Bioorganic Medicine Chemistry 2010; 18(1) 151-157.
[63] Borrelli, F, Maffia P, Pinto L, Ianaro A, Russo A, Capasso F, Ialenti A. Phytochemical
compounds involved in the antiinflamatory effect of propolis extract. Fitoterapia 2002;
73(suppl. 1). S53-S63.
[64] Barros MP, Sousa JP, Bastos JK, de Andrade SF. Effect of Brazilian green propolis on
experimental gastric ulcers in rats. Journal of Ethnopharmacology 2007; 110(3) 567-71.
[65] Juman S, Yasui N, Okuda H, Ueda A, Negishi H, Miki T, Ikeda K. Caffeic acid phenethyl
ester suppresses the production of adipocytokines, leptin, tumor necrosis factor -alpha
and resistin, during differentiation to adipocytes in 3T3-L1 cells. Biological Pharma‐
ceutical Bulletin 2011; 34(4):490-4.
[66] Teerasripreecha D, Phuwapraisirisan P, Puthong S, Kimura K, Okuyama M, Mori H,
Kimura A, Chanchao C . In vitro antiproliferative/cytotoxic activity on cancer cell lines
of a cardanol and a cardol enriched from Thai Apis mellifera propolis. BMC Comple‐
mentary and Alternative Medicine 2012; 2:27.
[67] Park YK, Koo, MH, Abreu JA. Antimicrobial activity of propolis on oral microrganisms.
Currents Microbiology 1998; 36 (1) 24-28.
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
161
[68] Bera A, Muradian LBA. Propriedades físico-químicas de amostras comerciais de mel
com própolis do Estado de São Paulo. Ciência e Tecnologia de Alimentos- Campinas
2007; 27(1) 49-52.
[69] Santos VR, Gomes RT, Teixeira KIR, Cortés ME. Antimicrobial activity of a propolis
adhesive formulation on different oral pathogens. Brazilian Journal of Oral Sciences
2007; 6 (22) 1387-1391.
[70] Júnior AF, Lopes MMR, Colombari V, Monteiro ACM, Vieira EP. Atividade antimi‐
crobiana de própolis de Apis mellifera obtidas em três regiões do Brasil. Ciência Rural-
Santa Maria 2006; 36: 294-297.
[71] Vargas, A. C.; Loguercio, A. P.; Witt, N. M.; Da Costa, M. M.; Sá E Silva, M.; Viana, L.
R. Atividade antimicrobiana “in vitro” de extrato alcoólico de própolis. Ciência Rural
2004; 34: 159-163.
[72] Tosi B, Donini A, Romagnoli C, Bruni A. Antimicrobial activity of some commercial
extracts of propolis prepared with different solvents. Phytotherapy Research 1996; 10(4)
335-336.
[73] Stepanović S, Antić N, Dakić I, Svabić-Vlahović M. In vitro antimicrobial activity of
propolis and synergism between propolis and antimicrobial drugs. Microbiological
Research 2003; 158(4) 353-357.
[74] Onlen Y, Duran N, Atik E, Savas L, Altug E, Yakan S, Aslantas O. Antibacterial activity
of propolis against MRSA and synergism with topical mupirocin. Journal of Alternative
and Complementary Medicine 2007; 13(7) 713-718.
[75] Santos VR, Gomes RT, Mesquita RA, De Moura MDG, França EC, Aguiar EG, Naves
MD, Abreu JAS, Abreu SRL. Efficacy of Brazilian Propolis Gel for the Management of
Denture Stomatitis: a Pilot Study. Phytotherapy Research 2008; 22(11) 1544–1547.
[76] Mello AM, Gomes RT, Lara SR, Silva LG, Alves JB, Cortés ME, Abreu SL, Santos VR.
2006. The effect of Brazilian propolis on the germ tube formation and cell wall of
Candida albicans. Pharmacologyonline 2006; 3: 352–358.
[77] De Nollin S, Borgers M. The effects of miconazole on the ultrastructure of Candida
albicans. Proceedings of Royal Society of Medicine 1977; 70(Suppl 1) 9-12.
[78] Tajima, H.; Kimoto, H.; Taketo, Y.; Taketo, A. Effects of synthetic hydroxyisothiocinates
on microbial systems. Biosciences Biotechnology and Biochemistry 1998; 62: 491-495.
[79] Siqueira AB, Gomes BS, Cambuim I, Maia R, Abreu S, Souza-Motta CM, de Queiroz
LA, Porto AL. Trichophyton species susceptibility to green and red propolis from Brazil.
Letters Applied Microbiology 2009; 48(1) 90-96.
[80] Ota C, Unterkircher C, Fantimato V, Shimizu MT. Antifungal activity of própolis on
different species of Candida. Mycoses 2001, 44(9-10) 375-378.
[81] Popova MP, Chinou IB, Marekov IN, Bankova VS. Terpenes with antimicrobial activity
from Cretan propolis. Phytochemistry. 2009; 70(10) 1262-1271.
Alternative Medicine
162
[82] Silva JC, Rodrigues S, Feás X, Estevinho LM. Antimicrobial activity, phenolic profile
and role in the inflammation of propolis. Food Chemistry Toxicology 2012; 50(5)
1790-1795.
[83] Havsteen BII. The biochemistry and medical significance of the flavonoids. Pharma‐
cology & Therapeutics 2002; 96(2-3) 67-202.
[84] Marquele FD, Stracieri KM, Fonseca MJ, Freitas LA. Spray-dried propolis extract. I:
physicochemical and antioxidant properties. Pharmazie 2006; 61(4) 325-330.
[85] Guo X, Chen B, Luo L, Zhang X, Dai X, Gong S. Chemical compositions and antioxidant
activities of water extracts of Chinese propolis. Journal of Agricultural Food Chemistry
2011; 59(23) 12610-12616.
[86] Messerli SM, Ahn MR, Kunimasa K, Yanagihara M, Tatefuji T, Hashimoto K, Mautner
V, Uto Y, Hori H, Kumazawa S, Kaji K, Ohta T, Maruta H. Artepillin C (ARC) in
Brazilian green propolis selectively blocks oncogenic PAK1 signaling and suppresses
the growth of NF tumors in mice. Phytotherapy Research 2009; 23(3) 423-427.
[87] Sud’ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfo‐
lomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant
properties. FEBS 1993; 329(1-2) 21-24.
[88] Mani F, Damasceno HC, Novelli EL, Martins EA, Sforcin JM. Propolis: Effect of different
concentrations, extracts and intake period on seric biochemical variables. Journal of
Ethnopharmacology 2006; 05(1-2):95-98.
[89] Vicentino, A. R. R.; Menezes, F. S. Atividade antioxidante de tinturas vegetais, vendidas
em farmácias com manipulação e indicadas para diversos tipos de doenças pela
metodologia do DPPH. Revista Brasileira de Farmacognosia 2007; 17(1) 384- 387.
[90] Sulaiman GM, Al Sammarrae KW, Ad'hiah AH, Zucchetti M, Frapolli R, Bello E, Erba
E, D'Incalci M, Bagnati R. Chemical characterization of Iraqi propolis samples and
assessing their antioxidant potentials. Food Chemistry Toxicology 2011; 49(9)
2415-2421.
[91] Russo A, Longo R, Vanella A. Antioxidant activity of própolis: role of caffeic acid
phenethyl ester and galangin. Fitoterapia 2002; 73(suppl. 1) S21-S29.
[92] Cigut T, Polak T, Gašperlin L, Raspor P, Jamnik P. Antioxidative activity of propolis
extract in yeast cells. Journal Agricultural Food Chemistry 2011; 59(21) 11449-11455.
[93] Guimarães NS, Mello JC, Paiva JS, Bueno PC, Berretta AA, Torquato RJ, Nantes IL,
Rodrigues T. Baccharis dracunculifolia, the main source of green propolis, exhibits
potent antioxidant activity and prevents oxidative mitochondrial damage. Food
Chemistry Toxicology 2012; 50 (3-4) 1091-1097.
[94] Gong P, Chen F, Liu X, Gong X, Wang J, Ma Y. Protective effect of caffeic acid phenethyl
ester against cadmium-induced renal damage in mice. Journal of Toxicology Science
2012; 37(2) 415-25.
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
163
[95] Nakamura T, Ohta Y, Ohashi K, Ikeno K, Watanabe R, Tokunaga K, Harada N.
Protective Effect of Brazilian Propolis Against Hepatic Oxidative Damage in Rats with
Water-immersion Restraint Stress. Phytotherapy Research 2012, Feb 1. doi: 10.1002/ptr.
4601. [Epub ahead of print]
[96] Vynograd N, Vynograd I, Sosnowski Z. A comparative multi-centre study of the
efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV).
Phytomedicine 2000; 7(1):1-6.
[97] Nolkemper S, Reichling J, Sensch KH, Schnitzler PMechanism of Herpes simplex virus
type 2 suppression by propolis extracts. Phytomedicine 2010; 17(2) 132-138.
[98] Huleihel M, Isanu V. Anti-herpes simplex virus effect of an aqueous extract of propolis.
Isr Medicine Association Journal. 2002; 4(11 Suppl) 923-927.
[99] Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK. Anti-HIV-1 activity of propolis
in CD4(+) lymphocyte and microglial cell cultures. Journal of Ethnopharmacology 2005;
102(2) 158-63.
[100] Drago L, De Vecchi E, Nicola L, Gismondo MR. In vitro antimicrobial activity of a novel
propolis formulation (Actichelated propolis). Journal of Applied Microbiology 2007;
103(5) 1914-1921.
[101] Schnitzler P, Neuner A, Nolkemper S, Zundel C, Nowack H, Sensch KH, Reichling J.
Antiviral activity and mode of action of propolis extracts and selected compounds.
Phytotherapy Research 2010; 24(Suppl 1) S20-S28. Erratum in: Phytotherapy Research
2010; 24(4) 632.
[102] Sartori G, Pesarico AP, Pinton S, Dobrachinski F, Roman SS, Pauletto F, Junior LC,
Prigol M. Protective effect of brown Brazilian propolis against acute vaginal lesions
caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti-
inflammatory mechanisms. Cell Biochem Funct. 2011 Oct 24. doi: 10.1002/cbf.1810.
[Epub ahead of print]
[103] Rao CV, Desai D, Rivenson A, Simi B, Amin S, Reddy BS. Chemoprevention of colon
carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Research 1995; 55(11)
2310-2315.
[104] Huang MT, Ma W, Yen P, Xie JG, Han J, Frenkel K, Grunberger D, Conney AH.
Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphor‐
bol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA,
RNA and protein in HeLa cells. Carcinogenesis 1996; 17(4) 761-765.
[105] Orsolić N, Basić I Antitumor, hematostimulative and radioprotective action of water-
soluble derivative of propolis (WSDP). Biomedicine and Pharmacotherapy 2005; 59(10)
561-570.
[106] Szliszka E, Czuba ZP, Domino M, Mazur B, Zydowicz G, Krol W. Ethanolic extract of
propolis (EEP) enhances the apoptosis- inducing potential of TRAIL in cancer cells.
Molecules 2009; 14(2) 738-754.
Alternative Medicine
164
[107] Endo S, Matsunaga T, Kanamori A, Otsuji Y, Nagai H, Sundaram K, El-Kabbani O,
Toyooka N, Ohta S, Hara. A selective inhibition of human type-5 17β-hydroxysteroid
dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis. Journal of
Natural Products 2012; 75(4) 716-21.
[108] Akao Y, Maruyama H, Matsumoto K, Ohguchi K, Nishizawa K, Sakamoto T, Araki Y,
Mishima S, Nozawa Y. Cell Growth inhibitory effect of cinnamic acid derivatives from
própolis on human tumor cell lines. Biological and Pharmaceutical Bulletin 2003; 26(7)
1057-1059.
[109] Awale S, Li F, Onozuka H, Esumi H, Tezuka Y, Kadota S. Constituents of Brazilian red
propolis and their preferential cytotoxic activity against human pancreatic PANC-1
cancer cell line in nutrient-deprived condition. Bioorganic Medical Chemistry 2008;
16(1)181-189.
[110] Li F, Awale S, Tezuka Y, Kadota SCytotoxicity of constituents from Mexican propolis
against a panel of six different cancer cell lines. Natural Products Communication 2010;
5(10) 1601-1606.
[111] Seda Vatansever H, Sorkun K, Ismet Deliloğlu Gurhan S, Ozdal-Kurt F, Turkoz E,
Gencay O, Salih B. Propolis from Turkey induces apoptosis through activating caspases
in human breast carcinoma cell lines. Acta Histochemica 2010; 112(6) 546-556.
[112] Sobočanec S, Balog T, Šariċ A, Mačak-Šafranko Ž, Štroser M, Žarković K, Žarković N,
Stojković R, Ivanković S, Marotti T. Antitumor effect of Croatian propolis as a conse‐
quence of diverse sex-related dihydropyrimidine dehydrogenase (DPD) protein
expression. Phytomedicine 2011; 18(10) 852-858.
[113] Badr MO, Edrees NM, Abdallah AA, El-Deen NA, Neamat-Allah AN, Ismail HT. Anti-
tumour effects of Egyptian propolis on Ehrlich ascites carcinoma. Veterinaria Italiana
2011; 47(3) 341-350.
[114] Benkovic V, Kopjar N, Knezevic AH, Dikiv D, Basic I, Ramic S, Viculin T, Knezevic F,
Orsolic N. Evaluation of Radioprotective Effects of Propolis and Quercetin on Human
White Blood Cells in Vitro. Biological. Pharmaceutical Bulletin 2008; 31(9) 1778-1785.
[115] Búfalo MC, Candeias JM, Sousa JP, Bastos JK, Sforcin JM. In vitro cytotoxic activity of
Baccharis dracunculifolia and propolis against HEp-2 cells. Natural Product Research
2010; 24(18) 1710-1718.
[116] Tanaka M, Okamoto Y, Fukui T, Masuzawa T. Suppression of interleukin 17 production
by Brazilian propolis in mice with collagen-induced arthritis. Inflammopharmacology
2012; 20(1)19-26.
[117] Bachiega TF, Orsatti CL, Pagliarone AC, Sforcin JM The Effects of Propolis and its
Isolated Compounds on Cytokine Production by Murine Macrophages. Phytotherapy
Research 2012; doi: 10.1002/ptr.3731.
[118] Okamoto Y, Tanaka M, Fukui T, Masuzawa T.Brazilian propolis inhibits the differen‐
tiation of Th17 cells by inhibition of interleukin-6-induced phosphorylation of signal
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
165
transducer and activator of transcription 3. Immunopharmacology and Immunotoxi‐
cology 2012; Feb 9. [Epub ahead of print] PMID: 22316079 [PubMed
[119] Dimov V, Ivanovska N, Bankova V, Popov S. Immunomodulatory action of propolis:
IV. Prophylactic activity against Gram-negative infections and adjuvant effect of the
water-soluble derivate. Vaccine 1992; 10(12) 817-823.
[120] Nunes A, Faccioli LH, Sforcin JM. Propolis: lymphocyte proliferation and IFN-g
production. Journal of Ethnopharmacology 2003; 87(1 )93-97.
[121] You KM, Son KH, Chang HW, Kang SS, Kim HP. Vitexicarpin, a flavonoid from the
fruits of Vitex rotundifolia, inhibits mouse lymphocyte proliferation and growth of cell
lines in vitro. Planta Medica 1998; 64(1) 546–550.
[122] Orsolic N, Sver L, Terzié S, Tadie Z, Basic I. Inhibitory effect of water-soluble derivative
of propolis and its polyphenolic compounds on tumor growth and metastasizing
ability: a possible mode of antitumor action. Nutrition and Câncer 2003; 47(2) 156-163.
[123] Orsolic N, Benkovic V, Knezevic AH, Kopjar N, Kosalec I, Bakmaz M, Mihaljevic Z,
Bendelja K, Basic I. Assessment by Survival Analysis of the Radioprotective Properties
of Propolis and Its Polyphenolic Compounds. Biological Pharmaceutical Bulletin 2007;
30(5) 946-951.
[124] Kimoto T, Arai S, Kohguchi M, Aga M, Nomura Y, Micallef MJ, Kurimoto M, Mito K.
Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian
propolis. Cancer Detect Prevention 1998; 22(6) 506-15.
[125] Missima F, Pagliarone AC, Orsatti CL, Araújo JP Jr, Sforcin JM. The Effect of propolis
on Th1/Th2 cytokine expression and production by melanoma-bearing mice submitted
to stress. Phytotherapy Research 2010; 24(10)1501-1507.
[126] Orsatti CL, Sforcin JM. Propolis immunomodulatory activity on TLR-2 and TLR-4
expression by chronically stressed mice. Natural Product Research 2012; 26(5) 446-453.
[127] Zedan H, Hofny ER, Ismail SA. Propolis as an alternative treatment for cutaneous
warts. International Journal of Dermatology 2009; 48(11) 1246-1249.
[128] de Sousa JP, Bueno PC, Gregório LE, da Silva Filho AA, Furtado NA, de Sousa ML,
Bastos JK. A reliable quantitative method for the analysis of phenolic compounds in
Brazilian propolis by reverse phase high performance liquid chromatography. Journal
of Separation Science 2007; 30(16) 2656-2665.
[129] Ramanauskiene K, Savickas A, Inkeniene A, Vitkevicius K, Kasparaviciene G, Briedis
V, Amsiejus A. Analysis of content of phenolic acids in Lithuanian propolis using high-
performance liquid chromatography technique. Medicina (Kaunas) 2009; 45(9) 712-717.
[130] Volpi N, Bergonzini G. Analysis of flavonoids from propolis by on-line HPLC-
electrospray mass spectrometry. Journal of Pharmacy and Biomedical Analysis 2006;
42(3) 354-361.
Alternative Medicine
166
[131] Gómez-Caravaca AM, Gómez-Romero M, Arráez-Román D, Segura-Carretero A,
Fernández-Gutiérrez A. Advances in the analysis of phenolic compounds in products
derived from bees. Journal of Pharmacology and Biomedicine Analysis 2006; 41(4)
1220-34.
[132] Watson DG, Peyfoon E, Zheng L, Lu D, Seidel V, Johnston B, Parkinson JA, Fearnley J.
Application of principal components analysis to 1H-NMR data obtained from propolis
samples of different geographical origin. Phytochemical Analysis 2006; 17(5) 323-331.
[133] Mutinelli F. The spread of pathogens through trade in honey bees and their products
(including queen bees and semen): overview and recent developments. Revue Scien‐
tifique et Technique 2011; 30(1) 257-271.
[134] Ceschel GC, Maffei P, Sforzini A, Lombardi Borgia S, Yasin A, Ronchi C. In vitro
permeation through porcine buccal mucosa of caffeic acid phenetyl ester (CAPE) from
a topical mucoadhesive gel containing propolis. Fitoterapia. 2002; 73 (Suppl 1) S44- S52.
[135] Iyyam Pillai S, Palsamy P, Subramanian S, Kandaswamy M. Wound healing properties
of Indian propolis studied on excision wound-induced rats. Pharmaceutical Biology
2010; 48(11):1198-1206.
[136] Dodwad V, Kukreja BJ. Propolis mouthwash: A new beginning. Journal of Indian
Society of Periodontology 2011; 15(2) 121-125.
[137] Eley BM. Antibacterial agents in the control of supragingival plaque: a review. British
Dental Journal 1999; 186(6) 286-296.
[138] Vervelle A, Mouhyi J, Del Corso M, Hippolyte MP, Sammartino G, Dohan Ehrenfest
DM. Mouthwash solutions with microencapsuled natural extracts: Efficiency for dental
plaque and gingivitis. Revue de Stomatologie et Chirurgie Maxillofacialle 2010;
111(3)148-151.
[139] Koo H, Cury JA, Rosalen PL, Ambrosano GM, Ikegaki M, Park YK Effect of a mouth‐
rinse containing selected propolis on 3-day dental plaque accumulation and polysac‐
charide formation. Caries Research 2002; 36(6):445-448.
[140] Cairo do Amaral R, Gomes RT, Rocha WMS, Abreu SLR, Santos VR. Periodontitis
treatment with brazilian green própolis gel. Pharmacologyonline. 2006; 3(3) 336-341.
[141] Martins RS, Péreira ES Jr, Lima SM, Senna MI, Mesquita RA, Santos VR Effect of
commercial ethanol propolis extract on the in vitro growth of Candida albicans collected
from HIV-seropositive and HIV-seronegative Brazilian patients with oral candidiasis.
Journal of Oral Sciences 2002; 44(1) 41-48.
[142] Jeon JG, Rosalen PL, Falsetta ML, Koo H. Natural products in caries research: current
(limited) knowledge, challenges, and future perspective. Caries Research 2011; 45(3)
243-263.
Propolis: Alternative Medicine for the Treatment of Oral Microbial Diseases
http://dx.doi.org/10.5772/54003
167
[143] Samet N, Laurent C, Susarla SM, Samet-Rubinsteen N. The effect of bee propolis on
recurrent aphthous stomatitis: a pilot study. Clinical Oral Investigation 2007;
11(2)143-147.
[144] Santos VR, Pimenta FJ, Aguiar MC, do Carmo MA, Naves MD, Mesquita RA. Oral
candidiasis treatment with Brazilian ethanol propolis extract. Phytotherapy Research
2005; 19(7) 652-654.
[145] Kalogeropoulos N, Konteles S, Mourtzinos I, Troullidou E, Chiou A, Karathanos VT.
Encapsulation of complex extracts in beta-cyclodextrin: an application to propolis
ethanolic extract. Journal of Microencapsulations 2009; 26(7) 603-613.
[146] Koru O, Toksoy F, Acikel CH, Tunca YM, Baysallar M, Uskudar Guclu A, Akca E,
Ozkok Tuylu A, Sorkun K, Tanyuksel M, Salih B. In vitro antimicrobial activity of
propolis samples from different geographical origins against certain oral pathogens.
Anaerobe 2007; 13(3-4) 140-145.
[147] De Luca MP. Verniz a base de quitosana contendo própolis verde brasileira: avaliação
da atividade antimicrobiana, citotoxicidade e perfil de liberação. Thesis. Universidade
Federal de Minas Gerais; 2011.
[148] da Silva WJ, Rached RN, Rosalen PL, Del bel Cury AA. Effects of nystatin, fluconazole
and propolis on poly(methyl methacrylate) resin surface. Brazilian Dent Journal 2008;
19(3)190-196.
[149] Sforcin JM, Bankova V. Propolis: is there a potential for the development of new drugs?
Journal of Ethnopharmacology 2010; 133(2) 253-260.
[150] Chan GC, Cheung KW, Sze DM. The Immunomodulatory and Anticancer Properties
of Propolis. Clinical Review of Allergy and Immunology 2012 Jun 17. [Epub ahead of
print] PMID: 22707327 [PubMed - as supplied by publisher]
[151] Chang FR, Hsieh YC, Chang YF, Lee KH, Wu YC, Chang LK. Inhibition of the Epstein-
Barr virus lytic cycle by moronic acid. Antiviral Research 2010; 85(3) 490-495.
[152] Iio A, Ohguchi K, Inoue H, Maruyama H, Araki Y, Nozawa Y, Ito M Ethanolic extracts
of Brazilian red propolis promote adipocyte differentiation through PPARγ activation.
Phytomedicine. 2010; 17(12) 974-9.
[153] Chuu CP, Lin HP, Ciaccio MF, Kokontis JM, Hause RJ Jr, Hiipakka RA, Liao S, Jones
RB. Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer
cells through inhibition of p70S6K and Akt signaling networks. Cancer Prevention
Research (Philadephia) 2012; 5(5) 788-797.
[154] Gjertsen AW, Stothz KA, Neiva KG, Pileggi R. Effect of propolis on proliferation and
apoptosis of periodontal ligament fibroblasts. Oral Surgery Oral Medicine Oral
Pathology Oral Radiology and Endodontics 2011; 112(6) 843-848.
Alternative Medicine
168
[155] Choudhari MK, Punekar SA, Ranade RV, Paknikar KM. Antimicrobial activity of
stingless bee (Trigona sp.) propolis used in the folk medicine of Western Maharashtra,
India. Journal of Ethnopharmacology 2012; 141(1) 363-367.
[156] Ha SK, Moon E, Kim SY. Chrysin suppresses LPS-stimulated proinflammatory
responses by blocking NF-κB and JNK activations in microglia cells. Neuroscience
Letters 2010; 485(3) 143-147.
[157] Watanabe MA, Amarante MK, Conti BJ, Sforcin JM. Cytotoxic constituents of propolis
inducing anticancer effects: a review.Journal of Pharmacy and Pharmacology 2011;
63(11) 1378-1386. 
[158] Salomão K, Pereira PR, Campos LC, Borba CM, Cabello PH, Marcucci MC, de Castro
SL. Brazilian propolis: correlation between chemical composition and antimicrobial
activity. Evidence Based Complementary and Alternative Medicine 2008; 5(3) 317-324.
[159] Salomão K, de Souza EM, Henriques-Pons A, Barbosa HS, de Castro SL. Brazilian Green
Propolis: Effects In Vitro and In Vivo on Trypanosoma cruzi. Evidence Based Comple‐
mentary and Alternative Medicine. 2011;2011:185918. Epub 2011 Feb 13. PMID:
19213854 [PubMed]
[160] Dias LG, Pereira AP, Estevinho LM. Comparative study of different Portuguese
samples of propolis: Pollinic, sensorial, physicochemical, microbiological characteri‐
zation and antibacterial activity. Food Chemistry Toxicology. 2012 Sep 5. pii:
S0278-6915(12)00640-0. doi: 10.1016/j.fct.2012.08.056. [Epub ahead of print] PMID:
22981908 [PubMed - as supplied by publisher]
[161] Mattigatti S, Ratnakar P, Moturi S, Varma S, Rairam S. Antimicrobial Effect of Con‐
ventional Root Canal Medicaments vs Propolis against Enterococcus faecalis, Staphylo‐
coccus aureus and Candida albicans. Journal of Contemporary Dental Practice.
2012;13(3)305-309.
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... Aspecto físico das amostras de própolis bruta verde (A) brasileira Fonte:Santos (2012). ...
... Aspecto físico das amostras de própolis bruta vermelha (B) brasileiraFonte:Santos (2012).Segundo Park et al. (2002), as própolis brasileiras, no que diz respeito a seu perfil químico, podem ser agrupadas em 13 grupos distintos. Como exemplo, têm--se as própolis, cujas origens botânicas localizam-se: cinco delas na região Sul, uma no Sudeste e sete tipos pertencentes à região Nordeste do país.A espécie Hypts divaricata e Dalbergia ecastophylum representa as principais fontes de resina pertencente à região Nordeste. ...
... The aqueous and alcoholic extracts of propolis do not cause irritation to the tissues and are considered relatively toxic. Refrens [4] Mineral substances (minor components).In propolis also exist few granules and variable quantities of impurities, the soluble and substances are in insignificant quantities. The proportion of the propolis components is revealed (table1). ...
... emulsionpolymerization.Referens [8], in situ polymerization,spray drying and coacervation.Referens [7] Capsule dosage forms occupy more than the total dosage forms on the market An example is Contac in which the active ingredients in the capsule are encapsulated in hundreds of microbeads in a sustained release form .Referens [4] Propolis has well-known antimicrobial activity as well as antioxidant, antitumoral, anti-inflammatory, and regenerative properties, but its effects on the immune response are not well understood. Furthermore, clinicalApplication of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility and, consequently, minimal systemic bioavailability. ...
Conference Paper
Full-text available
Propolis is a safe natural products which is a resinous hive material collected by honeybees from various plant sources. It was encapsulated with various materials such as oils, acids, various mixed granules, liquids, beeswax, Tetracycline and Azithromycin. This process was done by suspension device, the granular materials, mechanical stirring, freezing, drying and Spraying. It can be concluded, encapsulation of propolis with above materials is positive effective method to different application such as pharmaceuticals, health, Medical, etc. that was Included target.
... The lipids are collected by bees from plant resins [19][20][21]. In general, the organic components consist of carboxylic acids (20%), terpenoids (15%), steroids (12%), hydrocarbons (10%), sugars (6%), alkaloids (6%), flavonoids (4%), phenols (3%), vitamins (2%), amino acids (2%), ketones (2%), proteins (1%), and other compounds (14%) [22,23]. The most important biological active compounds are flavonoids, polyphenols, carboxylic acids, quercetins, fatty acids, cinnamic acid, esters, and terpenoids, such as pinocembrin, galangin, carboxylic acids, caffeic acid, caffeic acid phenethyl ester (CAPE), saponin, phorbol, naringenin, gallic acid, naringin, benzoic acids, amino acids, apigenin, coumaric acid, steroids, vitamins, reducing sugar, and essential oils [24,25], as summarized in Table 1. ...
Article
Full-text available
With technological advancements in the medicinal and pharmaceutical industries, numerous research studies have focused on the propolis produced by stingless bees (Meliponini tribe) and Apis mellifera honeybees as alternative complementary medicines for the potential treatment of various acute and chronic diseases. Propolis can be found in tropical and subtropical forests throughout the world. The composition of phytochemical constituents in propolis varies depending on the bee species, geographical location, botanical source, and environmental conditions. Typically, propolis contains lipid, beeswax, essential oils, pollen, and organic components. The latter include flavo-noids, phenolic compounds, polyphenols, terpenes, terpenoids, coumarins, steroids, amino acids, and aromatic acids. The biologically active constituents of propolis, which include countless organic compounds such as artepillin C, caffeic acid, caffeic acid phenethyl ester, apigenin, chrysin, galangin, kaempferol, luteolin, genistein, naringin, pinocembrin, coumaric acid, and quercetin, have a broad spectrum of biological and therapeutic properties such as antidiabetic, anti-inflammatory, antioxidant, anticancer, rheumatoid arthritis, chronic obstruct pulmonary disorders, cardiovascular diseases, respiratory tract-related diseases, gastrointestinal disorders, as well as neuroprotective, immunomodulatory, and immuno-inflammatory agents. Therefore, this review aims to provide a summary of recent studies on the role of propolis, its constituents, its biologically active compounds , and their efficacy in the medicinal and pharmaceutical treatment of chronic diseases.
... Most polyphenols are flavonoids, phenolic acids and ester, phenol aldehydes, ketone and other elements. [6][7][8] Propolis extract can be safely consumed on a daily basis as proven by toxicity tests. Such previous tests on BHK-21 fibroblast cells using Apis mellifera propolis extract confirmed that propolis is not toxic at concentrations below 3 mg/ml. ...
... Propolis as a complementary medicine has been used in the treatment of various diseases (Farooqui & Farooqui, 2012;Fukuda et al., 2015;Hu et al., 2005;Santos, 2012), and investigations in this regard have confirmed that propolis and its flavones could cause reduction in inflammation (Afsharpour et al., 2017;De Almeida & Menezes, 2002;Jalali et al., 2020). Furthermore, several studies have been conducted on animal models (Table 1). ...
Article
Full-text available
Rheumatoid arthritis (RA) is a chronic autoimmune disease in which inflammation and oxidative stress play a key role in its pathophysiology. Complementary therapies along with medications may be effective in the control of RA. Propolis is a natural substance extracted from beehives, which have confirmed anti‐inflammatory and antioxidant effects. The present study aimed to review the possible effects of propolis on inflammation, oxidative stress, and lipid profile in patients with RA. English articles in online databases such as PubMed‑Medline, AMED, Google Scholar, EMBASE, Scopus, and Web of Science databases were searched. Pieces of evidence show that supplementation with propolis may have therapeutic effects on RA patients. Due to increased inflammation and oxidative stress in the affected joints of RA patients, propolis could inhibit the inflammatory cascades by inhibiting the nuclear factor kappa B pathway and reducing reactive oxygen species, malondialdehyde, and interleukin‐17 by increasing some antioxidants. Therefore, inflammation and pain reduce, helping improve and control RA in patients. Further investigations are required with larger sample sizes and different doses of propolis to demonstrate the definite effects of propolis on various aspects of RA. Rheumatoid arthritis (RA) is an autoimmune and systemic disorder, and cytokines and inflammatory responses play a key role in its pathogenesis. Antioxidant supplements may help reduce the symptoms and improve the quality of life in RA patients. Propolis has numerous antioxidant and polyphenolic properties and may exert beneficial effects on the oxidative stress biomarkers and inflammation process.
... Antioxidant capacity of phenolic compounds led to prevent oxidation or destroy oxidizable compounds such as ascorbic acid and lipid and organize the growth of the plant. The RJ extraction way as well, may add to its effectiveness because of the high content of phenolic compounds that added to the aqueous extract more of antioxidant activity (Viuda-Martos et al., 2008;Santos, 2012). ...
... The bioactive components of RJ contributed to the increases in the contents of plant hormones and the activities of antioxidant enzymes, which in turn contributed significantly to the growth and yield of roselle plants (Table 11). In addition, the apparent efficacy of RJ may be due to it having good antioxidant activity associated with a high content of phenolic compounds (Santos, 2012). This ...
Article
For sustainable and organic farming, organic manures such as cattle manure (CMn) and bio-nutritious substances such as royal jelly (RJ) should be used as complete or at least partial alternatives to chemical fertilizers (CFs). Therefore, two consecutive trial seasons (2018 and 2019) were conducted to study the effect of soil fertilization with CMn and/or CFs in combination with foliar spraying with RJ on growth, yield, and chemical composition of roselle (Hibiscus sabdariffa L.) plant and seed. The results indicated that spraying roselle plants with RJ resulted in a significant increase in all parameters studied over the control; however, this increase was enhanced when RJ was combined with soil fertilization. The highest values for most of the growth traits, chemical composition of seeds, sepal anthocyanin and vitamin C contents, and sepal acidity were obtained by applying 2 or 4 g RJ L⁻¹ + (30 m³ CMn ha⁻¹ + 50% dose CFs). In addition, the highest values for yield components and plant chemical composition were obtained by applying 2 or 4 g RJ L⁻¹ + (0 m³ CMn ha⁻¹ + full dose CFs). The results also indicated that applying CMn in combination with RJ gave values mostly close to those of CFs treatment. In conclusion, the results recommend the use of RJ (2 g L⁻¹ as a foliar feeding) along with CMn (30 m³ ha⁻¹) as a partial alternative to chemical fertilizers for sustainably producing healthy roselle sepals.
... Indeed, the propolis contains large amounts of antioxidants owing to the extent of flavonoids and other effective compounds that prevent the oxidation and damage of the plant [33] and lead to organize plant growth [34]. Additionally, the effectiveness of propolis may also be related to the extraction method; as Santos [35] reported, the aqueous extract had the highest antioxidant activity because of its highest content of phenolic compounds. In this study, the use of high concentrations of propolis and low concentrations of salicylic acid, or the combination of the two agents (SA+PR treatment), provided the highest yields. ...
Article
Full-text available
Salicylic acid (SA) and propolis (PR) are known to regulate the physiological process and to have a relevant role in bioactive compounds content. Our experiment was designed to evaluate the effect of SA and PR application on the growth, yield, and quality parameters of tomato grown for the fresh market in field conditions in Egypt. We studied the effect of twelve treatments where SA (0.50, 1.00, 1.50, 2.00, and 2.50 mM) and PR (1, 2, 10, 20, and 100 mg propolis mL−1) were applied at increasing doses as a sole agent or combined each other (1.50 mM + 10 mg mL−1 for SA and PR, respectively). An untreated control was also considered. Tomato plants treated with SA (0.50, 1.00, and 1.50 mM) showed a significant effect in all traits especially SA1 (0.50 mM) in growth parameters and SA2 (1.00 mM) in pigment and antioxidant content. Propolis foliar application was more effective than SA as it revealed that raising the concentration of aqueous extract enhanced the growth parameters and pigment in tomato. The best result was obtained by the 10 mg mL−1 treatment. The effect of propolis on antioxidant enzymes varied as the 10 mg mL−1 treatment was effective on peroxidases and superoxide dismutase, while 100 mg mL−1 was more effective on catalase. Salicylic acid and propolis have a positive effect on both preserving tomato plants and on nutrient supply, so the mixed intermediate concentration (1.50 mM + 10 mg mL−1) is considered very effective and results in an improvement of all plant traits.
... El propóleo es un producto complejo que las abejas de diferentes especies obtienen al combinar resinas y bálsamos colectados de plantas, cera y secreciones salivales. Las colonias de abejas utilizan el propóleos para recubrir y aislar objetos o restos de animales al interior de su colmena, para cubrir grietas o vías de acceso a su colmena reduciendo así la entrada de frio y plagas y para barnizar las celdillas donde alojan a sus crías (Bankova, 2005;Rodrigues, 2012). ...
Article
Full-text available
El propóleo es un producto de las abejas que recolectan de la vegetación y que muestra acción antifúngica por la presencia de compuestos fenólicos y flavonoides. Cryptococcus neoformans es una levadura encapsulada que produce una infección micótica oportunista en hospederos inmunocompetentes como inmunocomprometidos. Debido a la resistencia que C. neoformans ha presentado a los antimicóticos comerciales, es necesario estudiar otras sustancias de origen natural con acción fungicida. En este estudio se evaluó el daño a la estructura de C. neoformans, proveniente de un aislamiento clínico, producido por un extracto etanólico de propóleo mexicano mediante Microscopía Electrónica de Barrido (MEB). Se cuantificaron los compuestos fenólicos y flavonoides de la resina; la evaluación de la actividad antifúngica se realizó mediante la prueba de inhibición del crecimiento radial y para determinar la Concentración Mínima Inhibitoria y Fungicida (CMI y CMF) se utilizó el método de macrodilución. El extracto de propóleo mexicano demostró tener un contenido óptimo de fenoles y flavonoides; una concentración de 2.5 mg/mL del extracto de propóleo provoca la formación de invaginaciones e irregularidades en la superficie del hongo produciendo una disminución del tamaño. Se demuestra la actividad anticriptococica de un extracto de propóleo al evidenciar el daño en la estructura celular, lo cual puede proporcionar la perspectiva de alternativa terapéutica para pacientes con diversas enfermedades producidas por este hongo, considerando ampliar la investigación del mecanismo de acción del propóleo como antifúngico.
... As mentioned before, for C3 and C5 (10% and 30% EEP, respectively), the surface of the films was more hydrophobic and for C4 with 20% EEP the film surface was hydrophilic. Propolis is a lipophilic material [32], hence, hydrophobic behavior should be expected. However, it seems that there is an optimal concentration of EEP in the formulations that influences hydrogen bond formation between hydrophilic groups of propolis and chitosan, changing the film surface nature from hydrophilic to hydrophobic [33]. ...
Article
Full-text available
RESUMO Como a própolis é amplamente utilizada no tratamento de doenças respiratórias é necessário o estudo da eficácia desse extrato, sendo então realizados testes em três bactérias modelo (Pseudomonas sp, Escherichia coli e Staphylococcus aureus) na proporção de própolis alcoólica 30%, própolis alcoólica 15%, álcool 30% e álcool 15% para testar as propriedades antimicrobianas da própolis e contribuir com estudos sobre produtos naturais que possam auxiliar na prevenção e tratamento de doenças. Palavras-chave: própolis, bactericida, bacteriostático, antimicrobiana, bactérias patogênicas ABSTRACT Because propolis is largely used in the treatment of respiratory diseases, the study of the efficiency of this extract was necessary.. Thus tests were performed on three bacteria (Pseudomonas sp, Escherichia coli and Staphilococcus aureus), in the proportions of 30% alcoholic propolis, 15% alcoholic propolis, 30% alcohol and 15% alcohol, in order to test their antimicrobial properties. The aim of these tests was to contribute to the study of natural products that can be helpful in the prevention and treatment of illnesses.
Article
Full-text available
This in vitro study aimed at investigating the possible radioprotective effects of natural substances propolis and quercetin on gamma-irradiated human white blood cells. The levels of primary DNA damage were studied by the alkaline comet assay, while the cytogenetic damage was evaluated using the analysis of structural chromosome aberration and cytokinesis-block micronucleus assay. The results obtained by all endpoints indicate acceptable toxicity profiles of propolis and quercetin in vitro, and also confirmed their radioprotective abilities. Propolis was found to be more effective in diminishing the levels of primary and more complex cytogenetic DNA damage in gamma-irradiated white blood cells. Data gathered in present study support the use of propolis and quercetin as non-toxic protective substances. However, to clarify the underlying mechanisms of their cyto/radioprotective activities, additional studies are necessary at both in vitro and in vivo levels.
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