review article recent progress of propolis for its...

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 697390 13 pageshttpdxdoiorg1011552013697390

Review ArticleRecent Progress of Propolis for Its Biological and ChemicalCompositions and Its Botanical Origin

Viviane Cristina Toreti Helia Harumi Sato Glaucia Maria Pastoreand Yong Kun Park

Department of Food Science College of Food Engineering State University of Campinas Monteiro Lobato Street n80PO Box 6177 13083-862 Campinas SP Brazil

Correspondence should be addressed to Yong Kun Park ykparkfeaunicampbr

Received 25 January 2013 Accepted 12 March 2013

Academic Editor Ewelina Szliszka

Copyright copy 2013 Viviane Cristina Toreti et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Propolis is the generic name given to the product obtained from resinous substances which is gummy and balsamic and which iscollected by bees from flowers buds and exudates of plants It is a popular folk medicine possessing a broad spectrum of biologicalactivities These biological properties are related to its chemical composition and more specifically to the phenolic compoundsthat vary in their structure and concentration depending on the region of production availability of sources to collect plant resinsgenetic variability of the queen bee the technique used for production and the season inwhich propolis is producedMany scientificarticles are published every year in different international journal and several groups of researchers have focused their attentionon the chemical compounds and biological activity of propolis This paper presents a review on the publications on propolis andpatents of applications and biological constituents of propolis

1 Introduction

Propolis is a resinous substance collected by Apis mellif-era from various tree buds which they then use to coathive parts and to seal cracks and crevices in the hive [1]Propolis has been used as a folk medicine since 300 BC [2]Recently numerous biological properties of propolis havebeen reported including cytotoxic antiherpes free radicalscavenging antimicrobial and anti-HIV activities [3ndash9]Because of the wide range of biological activities propolishas recently been extensively used in food and beverages toimprove health and prevent diseases [10ndash12]

The medical application of propolis preparation hasled to an increased interest in its chemical compositionsand its botanical origins because so far mainly polyphenolcompounds have been identified in propolis collected byApismellifera The flavonoids the main polyphenols in propolishave been found to be quantitatively or qualitatively variabledepending on the environmental plant ecology [13ndash16]

2 History of Propolis and the Researchon Propolis

The word ldquopropolisrdquo is derived from the Greek pro (for ldquoinfront of rdquo or ldquoat the entrance tordquo) and polis (ldquocommunityrdquo orldquocityrdquo) andmeans a substance in defense of the hive Propolisor bee glue is a brownish resinous material collected byworker bees from the leaf buds of numerous tree specieslike birch poplar pine alder willow palm Baccharis dra-cunculifolia andDalbergia ecastaphyllum [15 17 18] In orderto manufacture propolis bees may also use material activelysecreted by plants or exuded from wounds in plants [18]

Propolis has been used by man since early times forvarious purposes as an antiseptic antioxidant antiinflamma-tory and an adhesive and to seal cracks to protect woodenand other surfaces The bees use propolis to repair combsto strengthen the thin borders of the comb and to makethe entrance of the hive weathertight or easier to defendPropolis is also used as an ldquoembalmingrdquo substance to cover

2 Evidence-Based Complementary and Alternative Medicine

(a) (b)

Figure 1Apis mellifera collecting propolis ofBaccharis dracunculifolia to production propolis in Brazil (a)Apis mellifera collecting leaf apicesBaccharis dracunculifolia (b) deposition of green propolis cracks in the hive

the carcass of a hive invader which the bees have killed butcannot transport out of the hive The bees cover the invaderwith propolis and wax and the remains are left at the bottomor on one of the walls of the hive [2 19] Figure 1 illustratesthe Apis mellifera collecting resinous material from leaf budsof Baccharis dracunculifolia (a) and the deposition of greenpropolis in the hive (b)

In early records are mentioned substances that cast doubton the use or not of propolis In Genesis (c 1700 BC) tzoriwas taken to Egypt once with honey and its healing prop-erties are noted three times in Jeremiah Twice tzori camefromGilead but it was not balm of Gilead which is producedfrom a tree Commiphora opobalsamum Assis believed thatldquoblack waxrdquo referred to in the Egyptian Ebers papyrus (c 1550BC)may have been propolis He also considered that Hebrewtzori was an early word for propolisThis occured six times inthe Hebrew scriptures and was usually translated as balm orbalsam [19]

Egyptians knew very well the antiputrefactive propertiesof propolis andused it to embalm cadaversGreek andRomanphysicians Aristoteles Dioscorides Pliny and Galen werefamiliar with the medicinal properties of propolis It is notknown what methods were used for harvesting it in theancient world although writers in Greece and Rome werefamiliar with it The Greek Historia Animalium referred to asubstance mitys which was probably propolis as ldquoa cure forbruises and suppurating soresrdquo According to Varro in Romepropolis was used by physicians in making poultices and forthis reason it brings even a higher price than honey on theVia Sacra [19]

The propolis was employed as an antiseptic and cica-trizant in wound treatment and as a mouth disinfectantwith these uses being perpetuated in the Middle Ages andamong Arab physicians Propolis was also recognized byother peoples unrelated to the Old World civilizations Incasemployed propolis as an antipyretic agent and the Londonpharmacopoeias of the seventeenth century listed propolisas an official drug Between the seventeenth and twentiethcenturies the propolis became very popular in Europe onaccount of its antibacterial activity [18]

21 Publications and Patents The first work indexed byChemical Abstracts on propolis was in 1903 and the firstpatent was described in 1904 (USAmdashComposition for treat-ing pins and piano strings) One hundred and nine years afterthe first publication in the Chemical Abstract the number ofpublications on propolis reached 3880 in journal and 2884in patents

Figure 2 shows the number of publications on propolisover the decades data were obtained by searching theChemi-cal AbstractsThe global interest in propolis research presentstwo justifications according to Pereira et al [20] the first topresent diverse biological properties and the second by highadded value the sale price of a bottle in Brazil is about 5 to 10real

The scientific production about propolis by documenttype is the majority about journal and patents as shown inFigure 3

The processed patent documents contain highly valuablelegal economic and technical information hence the resultsobtained from their processing make it possible to obtainhighly valuable information to reach conclusions useful askey elements for the design of RampD technological surveil-lance market studies and marketing strategies [21]

Since the first patentwas filed anduntil today it is possibleto see that there was a considerable increase in the number ofpatents in the last thirty years (Figure 4)

According to profile of patents shown in Figure 5 ChinaJapan and Russia are those that holdmost of the patentsThisfact can be justified by China and Russia being the largestproducers of propolis Today 42 of patents are Chinese(Figure 5) and the first Chinese patent appeared in 1993(on ldquoProcess for productionmouth freshenerrdquo)The Japanesehave 15 of patents and the first appeared in 1988 (aboutldquoDeodorants controlling mouth odorrdquo) The first patent wasobtained in 1968 on Russian ldquoToothpasterdquo and represented12 of patents Brazil deposited its first patent in 1997 onldquoDental gelrdquo Some patents are presented in Table 1

Suarez et al [21] noted the trend of patent applicationsaccording to application area for the period 1972ndash2000and observed a high incidence of products with medicinal

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Relationship of some of the 2884 international patents (Chemical Abstracts)

Year Country Title Register1904 USA ldquoComposition for treating piano pins and stringsrdquo US7674991920 Unavailable ldquoPaint vehiclesrdquo GB1469861921 USA ldquoWaterproof paintrdquo US14012611952 Unavailable ldquoTooth paste and oral disinfectantrdquo AT1720631969 USSR ldquoA dental elixirrdquo SU2401821979 Romania ldquoA powder containing soluble propolisrdquo RO670361990 Japan ldquoProcessed food containing propolisrdquo JP02154652

1995 USA ldquoTreatment of acnePharmaceutical compositions for treatment of acne containingextracts of propolis verbascum etcrdquo US5399349

2009 Turkey ldquoUse of propolis as base material under dental inlays and as filling material for rootcanalsrdquo TR2009000486

2011 Turkey ldquoExtract of propolis and Cramp Bark (Viburnum opulus) with high content of phenoliccompounds useful as natural remedyrdquo TR2011000075

2012 Korea ldquoMethod for manufacturing functional food containing propolisrdquo KR2012136769

5 5 6 1 19 44 196 393994

01000200030004000500060007000

Num

ber o

f pub

licat

ions

Publication decade

1911

ndash192

0

1921

ndash193

0

1931

ndash194

0

1941

ndash195

0

1951

ndash196

0

1961

ndash197

0

1971

ndash198

0

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

-201

2

Tota

l

3864

1305

6838

Figure 2 Scientific productivity on propolis between the decades(Chemical Abstracts)

4 43 7 63 5 2 5 18268

0500

100015002000250030003500400045005000

Num

ber o

f pub

licat

ions

Document type

Book

Clin

ical

tria

l

Com

men

tary

Con

fere

nce

Diss

erta

tion

Edito

rial

Jour

nal

Lette

r

Pate

nt

Revi

ew

Hist

oric

al

3880

2884

Figure 3 Scientific production on propolis by document type(Chemical Abstracts)

and nutraceutical properties and with dermatological appli-cations

The scientific production on propolis and healthy patentsbetween the decades in shown in Figure 6

2 1 1 0 0 4 5 20 94

459601

0200400600800

10001200140016001800

Num

ber o

f pat

ents

Publication decade

1911

ndash192

0

1901

ndash191

0

1921

ndash193

0

1931

ndash194

0

1941

ndash195

0

1951

ndash196

0

1961

ndash197

0

1971

ndash198

0

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201

3

1697

Figure 4 Scientific production on propolis by patents (ChemicalAbstracts)

436353

334224

747252

3921

79

0 200 400 600 800 1000 1200 1400ChineseJapaneseRussianKoreanEnglish

RomanianGerman

PortugueseFrenchItalian

Number of patents

Lang

uage

s

1200

Otherlanguages

Figure 5 Scientific production onpropolis by patents and languages(Chemical Abstracts)

The inventions processed according to their prioritycountry are which shown in Figure 7 in which the highestnumber of filings corresponds to China (476) followed byJapan (177) Korea and Russian with 77 and 29 and filingsrespectively Japan imports almost all the propolis used inthe country 80 comes from Brazil and 10 from China


8

97

529

152

0

100

200

300

400

500

600

Num

ber o

f pat

ents

Patents on propolis and healthy

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201

3Figure 6 Scientific production on propolis and healthy by patentsbetween the decades (Chemical Abstracts)

476

177

7729 17 6 1 1 1 10

100

200

300

400

500

Language

Num

ber o

f pat

ents

on p

ropo

lisan

d he

alth

y

Chin

ese

Japa

nese

Kore

an

Russ

ian

Engl

ish

Ger

man

Czec

h

Italia

n

Port

ugue

se

Span

ish

Figure 7 Scientific production on propolis and healthy by patentsand languages (Chemical Abstracts)

Table 2 Brazilian propolis export market [49]

Year Quantity export(Kg)

Value(U$S)

Value per kilo(U$SKg)

2010 51213 4346604 84872011 38845 4537727 116812012 41721 5401643 12947

and other countries and this is shown in their inventionssince in the analysis carried out to the content of the Japaneseinventions we can see that the Brazilian propolis is the targetof invention [21]

Six percent of patents filed by 2012 refers to the use ofpropolis for dental treatment (Figure 8) According to Pereiraet al [20] this is one of the most widely studied applicationsof propolis worldwide

According to the Ministry of Development Industry andForeign Trade of Brazil [22] the Brazilian export marketof propolis in the year of 2012 was 41721 Kg correspondingabout $5401643 These values can be observed in Table 2

81

25 22 11 10 9 7 2 2 1 1 1

172

020406080

100120140160180200

Num

ber o

f pat

ents

in d

entis

try

Languages

Chin

ese

Engl

ish

Russ

ian

Kore

an

Ger

man

Japa

nese

Port

ugue

se

Fren

ch

Rom

ania

n

Bulg

aria

n

Mol

davi

an

Turk

ishTo

tal p

aten

tsby

lang

uage

s

Figure 8 Scientific production on propolis for dental treatment bypatents and languages (Chemical Abstracts)

Analyzing the data it is possible to observe that there wasa drop in sales in 2011 compared to 2010 Regarding the valueof the product there was an increase of over 50 in 2012compared to 2010 According to Aga et al [23] the countrythat buys Brazilian propolis is Japan and its extensive use infoods and beverages intended tomaintain or improve humanhealth

3 Chemical Composition and Propolis Activity

31 Chemical Composition Propolis is a complex resinousmixture which contains approximately 50 of resin andbalsam 30 of wax 10 of essential and aromatic oils5 of pollen and 5 of impurities [24] The chemicalcomposition of propolis is highly variable mainly due to thevariability of plant species growing around the hive fromwhich the bees collect the exudates [18 25ndash28] Additionallypropolis composition can vary depending on the seasonalityillumination altitude collector type and food availabilityand activity developed during propolis exploitation [29ndash33]

Much work has been conducted on the chemical com-position and biological activities Until now more than 300chemical constituents have been identified in propolis fromdifferent regions [34] The main chemical classes present inpropolis are flavonoids phenolics and aromatic compounds(Figure 9) [35 36] Propolis also contains some volatile oilsterpenes and bee wax but these compounds are not believedto contribute as significantly to the chemical properties andeffects of propolis [36]

Many analytical methods have been used for separationand identification of propolis constituents Differents com-pounds have been identified in ethanol extracts of propolis(Table 3)

32 Method of Extraction Themethod of extraction and sol-vent can change the chemical composition of propolis extractCommercial products such as tablets capsules ampoulesand syrups are prepared with ethanolic extract of propolisMethanol is only used for research purposes Some varieties


Table 3 Identified compounds in ethanol extracts of propolis

Sample Compounds identified Reference

Bulgarian propolis 37-Dihydroxy-5-methoxyflavanone 25-dihydroxy-7-methoxyflavanone [50]

North and SouthBulgaria

Dihydrocaffeic acidDihydroferulic acidDihydroxyacetophenone hydroxymethoxyacetophenone120573-Phenethyl alcoholBenzyl alcohol pinobanksinPinostrobinDimethyl kaempferol

[51]

BrazilSao Paulo state 3-Prenyl-4-dihydrocinnamoloxynnamic acid [23]

BrazilSao PaulostateBotucatu city 9-E and 9-Z 22-Dimethyl-6-carboxyethenyl-8-prenyl-2H-benzopyran [52]

BrazilSao Paulo state

Dehydroabietic acidAbietic acid120573-AmyrineTriterpenic alcohol of amyrineLanosterol isomer with 9(11) double bond

[53]

Not reported

(E)-23-Dihydroconiferyl p-coumarate(E)-3-23-Dihydro-2-[2-[(E)-pcoumaroyloxy]-1-methylethyl]-5-benzofuranyl-2-propenoic acid(E)-4-(23-Dihydrocinnamoyloxy) cinnamic acid(E)-3-(22-Dimethyl-34-dihydro-3-hydroxy-2H-1-benzopyran-6-yl)-2-propenoic acid(E)-3-[23-Dihydro-2-(1-methylethenyl)-5-benzofuranyl]-2-propenoic acid(E)-3-[23-Dihydro-2-(1-methylethenyl)-7-prenyl-5-benzofuranyl]-2-propenoic acid(E)-3-3-[(E)-4-(23-Dihydrocinnamoyloxy)-3-methyl-2-butenyl]-4-hydroxy-5-prenylphenyl-2-propenoic acidDihydrokaempferol (aromadendrin)6-Methoxykaempferol4-Hydroxy-3-prenylbenzoic acidPlicatin BCapillartemisin A

[54]

JapanOkinawa Prokinawan [55]

Brazilian propolis type 6 Hyperibone A [56]

MexicoChampoton

1-(3101584041015840-Dihydroxy-21015840-methoxyphenyl)-3-(phenyl)propane(z)-1-(21015840-Methoxy-4101584051015840-dihydroxyphenyl)-2-(3-phenyl)propene3-Hydroxy-56-dimethoxyflavan(minus)-7-Hidroxyflavanone(minus)-Mucronulatol(minus)-Arizonicanol a(+)-Vestitol(minus)-Melilotocarpan a(minus)-Melilotocarpan d(+)-Pinocembrin

[57]

Greece (six regions)

18-Hydroxyabieta-8 1113-trieneDihydroxyabieta-81113-triene hydroxydehydroabietic acid18-Succinyloxyabietadiene18-Succinyloxyabietadiene (isomer)18-Succinyloxyhydroxyabietatriene

[58]

Kenyan propolis

Tetrahydrojusticidin B6-MethoxydiphyllinPhyllamyricin CMacaranginSchweinfurthin ASchweinfurthin B

[59]


Table 3 Continued


IndonesiaEast JavaprovinceBatu city

5-Pentadecylresorcinol5-(81015840z 111015840z Heptadecadienyl)-resorcional5-(111015840z-Heptadecenyl)-resorcinol5-HeptadecylresorcionalPropolin dPropolin cPropolin fPropolin g

[60]

Jordanian propolis 24(z)-1120573-3120573-Dihydroxyeupha-724-dien-26-oic acid [61]

Honduras (E Z)-Cinnamyl cinnamate [62]

Solomon island Solophenol (A) [63]

Table 4 Propolis of different geographic regions and their principal plantsrsquo sources of chemical compounds (from Bankova 2005)

Geographic origin Plant source ReferencesBulgaria Populus nigra P italic [16 50 63]Albania Populus nigra [63]Bulgaria Populus tremula [16]Mongolia Populus suaveolens [16 63]USA (mainland) Populus fremontii [16]USA (Hawaiian islands) Plumeria acuminate Plumeria acutifolia [16]United Kingdom Populus euramericana [16]Hungary Betula Populus Pinus Prunus and Acacia spp Aesculus hypocastane [16]Poland Betula Alnus spp [16]Equatorial regions Delchampia spp [16]Equatorial regions Clusia spp [16 64]Australia Xanthorrhoea [2]North temperate zone Poplar birch elm alder beech conifer and horse chestnut [2]Europe North America nontropic regions ofAsia (poplar propolis) Populus spp of section Aigeiros most often P nigra L [1 34 65]

Russia (birch propolis) Betula verrucosa Ehrh [66]Brazil (green-alecrim-propolis) Baccharis spp Predominantly B dracunculifolia DC [14 67]

Cuba Venezuela Clusia minor [16 68ndash70]Clusia spp

South Brazil (type 3) Argentine and Uruguay Populus alba [71]Brazil (type 6 from northeastern Brazil) Hyptis divaricate [14]Brazil (type 13 from northeastern Brazil) Dalbergia ecastaphyllum [17 42]

of propolis have solubility in water thereby extracting watershould also be considered for study [35]

33 Origin Botanical The materials available to bees forproduction of propolis are substances actively secreted byplants as well as substances exuded from wounds in plantslipophilicmaterials on leaves and leaf buds resins mucilagesgums lattices and so forth [37]

The composition of the plant source determines thechemical composition of bee glue and it is dependent onits geographical location as a result its biological activity isclosely related to the vegetation native to the site of collection[14 38 39]

Bankova [38] discusses the diversity of the chemicalcomposition of propolis and the problem of standardizationThe issue is based on the chemical composition of propoliswhich varies with the plant source collection Dealing withreliable criteria for chemical standardization of differentpropolis types is needed but such generally accepted criteriado not yet exist There is still a lot of work to be doneto achieve standardization of other propolis types Workingwith standardization material will allow scientists to connecta particular chemical propolis type to a specific type ofbiological activity and formulate recommendations Table 4illustrates propolis of different geographic regions and theirprincipal plant sources of chemical compounds


Table 5 Classification of Brazilian propolis according to their physicochemical characteristics and location [17 41]

Groups Ethanolic extract of propolisColor Origin of propolis

Group 1 (RS5) Yellow SouthernGroup 2 (RS1) Brown SouthernGroup 3 (PR7) Dark brown SouthernGroup 4 (PR8) Brown SouthernGroup 5 (PR9) Greenish brown SouthernGroup 6 (BA11) Reddish brown NortheastGroup 7 (BA51) Greenish brown NortheastGroup 8 (PE5) Dark brown NortheastGroup 9 (PE3) Yellow NortheastGroup 10 (CE3) Dark yellow NortheastGroup 11 (PI11) Yellow NortheastGroup 12 (SP12) Green or greenish brown SoutheastGroup 13 (AL) Red Northeast

H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

Kaempferol Quercetin

Chrysin

Pinocembrine 120588-Coumaric acid

Saccharin

Galangin

CH=CH-COOH

35 Diprenyl-120588-coumaric (artepellin C)

Figure 9 Some typical flavonoids and phenolics present in green propolis


Table 6 Chemical constituents of propolis that possess known pharmacological activities

Chemical compounds Activities ReferencesAcacetin Anti-inflammatory [72]Apigenin Anti-inflammatory [72]

Artepillin CAntimicrobialAntitumor activityAntioxidative

[23 41 73ndash75]

Caffeic acid phenethyl ester Antitumor activityAnti-inflammatory [76 77]

Chrysin Anti-inflammatory [72]

Caffeic acid

AntibacterialAntifungalAntiviralAnti-inflammatory

[72 78ndash80]

Cinnamic acid Anti-inflammatory [72]Dicaffeoylquinic acid derivatives Hepatoprotective [81]Ferulic acid Anti-inflammatory [72]Galangin Anti-inflammatory [72]Gallic acid Anti-inflammatory [72]Moronic acid Anti-HIV [9]Isoferulic acid Anti-inflammatory [72]Pinostrobin Local anesthesia [82]Protocatechuic acid Anti-inflammatory [72]

Pinocembrin

AntibacterialAntifungalAntimoldLocal anesthesia

[79 80 82 83]

Propofol Antioxidative [7]120588-Coumaric acid Antibacterial [74]m-Coumaric acid Anti-inflammatory [72]o-Coumaric acid Anti-inflammatory [72]

Quercetin

Anti-inflammatoryAntiviralAntihistamineUlcer healingCapillary strengthening

[41 78]

Volatile constituents(phenols esters terpenoids etc) Antibacterial [64]

22-Dimethyl-6-carboxyethyl-2H-1-benzopyran Antimicrobial [81]3-[34-Dihydroxy-5-prenylphenyl]-2-(E)-propenoic acid Antioxidative [84]

34 Classification of Brazilian Propolis It was found thatpropolis from several regions of Brazil show different chemi-cal composition depending on the local flora at the site of col-lection [40] The propolis from Brazil was classified in typesaccording to its geographical origin chemical compositionand source plant as shown in Table 5 [17 41 42] More studiesshould be done in order to standardize propolis

35 Activity of Propolis It is important to note that mostof the latest investigations on new propolis constituents areconnected to their biological activity This information issummarized in Table 6 Some compounds frompropolis haveantibacterial activity antitumor activity and antiinflamma-tory activity antioxidative and hepatoprotective action

According to Bankova et al [34] relating the chemicalconstituents of propolis with biological activity enables thestandardization of the application of propolis Kumazawaet al [28] report that differences in the chemical compositionof propolis from different sources change the spectrum ofbiological activity of propolis

Some studies have been conducted correlating chemicalcomposition and biological activity but no tested compoundswere isolated [43ndash47]

4 Application in Medicine and Dentistry

Propolis has been found to have awide spectrumof biologicaland pharmaceutical properties and has been demonstrated


Table 7 Recent studies on application of propolis in medicine

Application in medicineGeographic origin of propolis Activity attributed Test performed ReferencesBrazil (southern) Anti-HIV activity In vitro (H9 Lymphocytes) [9]Brazil Anticancer activity In vivomdashmice (pulmonary tumors) [85]Brazil Anticancer activity In vitro (human tumor cell lines) [86]Brazil (group 3 and group 12) Suppression of dioxin In vitro [87]

Chile Antioxidant and anticancer

In vitro(KB cellsmdashhuman mouth epidermoidcarcinoma cellsCaco-2 cellsmdashhuman colonadenocarcinoma cells)

[88]

Brazil Anticancer activity In vitro and in vivo (retinal damage) [89]Brazil (group 3 group 12 and bud resins ofbotanical origin) Anticancer activity In vitro (human prostate epithelial cells) [90]

Brazil Antiinfluenza virus activity In vivo-mice (influenza virus) [91]Jordanian Antibacterial In vitro [92]

Tunisia Anticancer activity In vitro (cancer cell linesmdashHT29 A549Hep-2 raw2647 and Vero) [93]

Brazil (group 12 and artepellin C) Immunosuppressant In vitro (CD4 T cell) [94]Portugal Anticancer activity In vitro (human renal cancer) [95]Israel (Kibbutz Yad Mordecai and CAPE) Anticancer activity In vitro (human T-cell lines) [96]Brazil Anticancer activity In vitro (human breast cancer MCF-7 cells) [97]Brazil (group 12 and group 13) Anticancer activity In vitro (human cell lins of leukemia) [98]CAPE (derived from honeybee hive propolis) Anticancer activity In vitro (human prostate cancer cells) [99]Brazil Anticancer activity In vivomdashmice (skin carcinogenesis) [100]Poland Anticancer activity In vitro (U87MG human glioblastoma) [101]

Table 8 Recent studies on application of propolis in dentistry

Application in dentistryGeographic origin of propolis Activity attributed Test performed ReferencesJapan Inhibited glucosyltransferase activity In vivomdashrats [102]Brazil (extracts of propolis from the states ofMinas Gerais Sao Paulo Goias Mato Grossodo Sul Parana and Rio Grande do Sul)

Inhibited glucosyltransferase activity In vitro [8]

Brazil (extracts of propolis from the states ofMinas Gerais and Rio Grande do Sul) Cariostatic effect In vivomdashrats [103]

Brazil (extracts of propolis from the states ofMinas Gerais and Rio Grande do Sul) Inhibited glucosyltransferase activity In vitro [104]

Brazil (Minas Gerais state)Antibacterial activityInhibition of cell adherenceInhibition of water-insoluble glucan formation

In vitro [105]

Brazil (extracts of propolis from the states ofMinas Gerais and Rio Grande do Sul) Cariostatic effect Human [106]

Brazil (extract of propolis from Bahia state) Exceptionally effective against Streptococcusmutans In vitro [107]

Apigenin and tt-farnesol Glucosyltransferase activity In vivomdashrats [108]Apigenin and tt-farnesol (association) Cariostatic effect In vitro [109]

Brazil (Isolated fractions) Cariostatic effect In vitro and invivo [110]

Brazil (Bahia state) Cariostatic effect In vivomdashrats [111]Brazil (extracts of propolis) Cariostatic effect Human [112]

Tunisia Cariogenic activityInhibition oral biofilm formation In vitro [93]

Korea Antibacterial activity In vitro [113]


to have direct antimicrobial effects in vitro [48] Some recentstudies suggested that propolis can be used in medicine anddentistry Tables 7 and 8 illustrate some studies that show theapplication of propolis in medicine and dentistry

5 Conclusions

Propolis has been used extensively as a folk medicine becauseof its special chemical components strong pharmacologicalproperties and low toxicityThiswide spectrumof therapeuticeffects makes propolis a potential candidate in several clinicalscenarios Clinical studies are now also in progress to verifythe effects of propolis in the prevention and treatment ofdiseases

The application of propolis is mostly in the drug or foodmanufacture in the form of mixtures Current opinion is thatthe use of standardized preparations of propolis is safe andless toxic thanmany syntheticmedicines but the componentsof propolis are variable and it is difficult to standardize andapply propolis Robust manufacturing processes standard-ized quality controls and good design clinical trials are allcritical steps in verifying these claims

References

[1] W Greenaway T Scaysbrook and F RWhately ldquoThe composi-tion and plant origin of propolis a report of work Oxfordrdquo BeeWorld vol 71 no 3 pp 107ndash118 1990

[2] E L Ghisalberti ldquoPropolis a reviewrdquo Bee World vol 60 no 2pp 59ndash84 1979

[3] TMatsuno YMatsumotoM Saito and JMorikawa ldquoIsolationand characterization of cytotoxic diterpenoid isomers frompropolisrdquo Zeitschrift fur Naturforschung C vol 52 no 9-10 pp702ndash704 1997

[4] N Vynograd I Vynograd and Z Sosnowski ldquoA compara-tive multi-centre study of the efficacy of propolis acyclovirand placebo in the treatment of genital herpes (HSV)rdquo Phy-tomedicine vol 7 no 1 pp 1ndash6 2000

[5] TKimotoMAgaKHino et al ldquoApoptosis of human leukemiacells induced by Artepillin C an active ingredient of BrazilianpropolisrdquoAnticancer Research vol 21 no 1 A pp 221ndash228 2001

[6] T Kimoto S Arai M Kohguchi et al ldquoApoptosis and suppres-sion of tumor growth by Artepillin C extracted from Brazilianpropolisrdquo Cancer Detection and Prevention vol 22 no 6 pp506ndash515 1998

[7] P Basnet T Matsuno and R Neidlein ldquoPotent free radicalscavenging activity of propol isolated from Brazilian propolisrdquoZeitschrift fur Naturforschung C vol 52 no 11-12 pp 828ndash8331997

[8] Y K Park M H Koo J A S Abreu M Ikegaki J A Curyand P L Rosalen ldquoAntimicrobial activity of propolis on oralmicroorganismsrdquo Current Microbiology vol 36 no 1 pp 24ndash28 1998

[9] J Ito F R Chang H K Wang et al ldquoAnti-AIDS agents 48Anti-HIV activity of moronic acid derivatives and the newmelliferone-related triterpenoid isolated from Brazilian propo-lisrdquo Journal of Natural Products vol 64 no 10 pp 1278ndash12812001

[10] G A Burdock ldquoReview of the biological properties and toxicityof bee propolis (propolis)rdquo Food and Chemical Toxicology vol36 no 4 pp 347ndash363 1998

[11] V Bankova and N Marekov ldquoPropolis-chemical compositionand standardizationrdquo Farmatsiya vol 32 pp 8ndash18 1984

[12] C Garcia-Vigueira W Greenaway and F Whatley ldquoComposi-tion of propolis from two different Spanish regionsrdquo Zeitschriftfur Naturforschung C vol 47 pp 634ndash637 1992

[13] B Konig ldquoPlant sources of propolisrdquo Bee World vol 66 no 4pp 136ndash139 1985

[14] Y K Park S M Alencar and C L Aguiar ldquoBotanical originand chemical composition of Brazilian propolisrdquo Journal ofAgricultural and Food Chemistry vol 50 no 9 pp 2502ndash25062002

[15] Y K Park J F Paredes-Guzman C L Aguiar S M Alencarand F Y Fujiwara ldquoChemical constituents in Baccharis dracun-culifolia as the main botanical origin of Southeastern Brazilianpropolisrdquo Journal of Agricultural and Food Chemistry vol 52no 5 pp 1100ndash1103 2004

[16] M C Marcucci ldquoPropolis chemical composition biologicalproperties and therapeutic activityrdquo Apidologie vol 26 no 2pp 83ndash99 1995

[17] A Daugsch C S Moraes P Fort and Y K Park ldquoBrazilianred propolismdashchemical composition and botanical originrdquoEvidence-Based Complementary and Alternative Medicine vol5 no 4 pp 435ndash441 2008

[18] S Castaldo and F Capasso ldquoPropolis an old remedy used inmodern medicinerdquo Fitoterapia vol 73 supplement 1 pp S1ndashS62002

[19] E Crane ldquoThe past and present importance of bee products tomanrdquo inBee ProductsmdashProperties Applications andApitherapyA Mizrahi and Y Lensky Eds pp 1ndash13 Plenum Press NewYork NY USA 1997

[20] A S Pereira F RM S Seixas and F R AquinoNeto ldquoPropolis100 anos de pesquisa e suas perspectivas futurasrdquo QuımicaNova vol 25 no 2 pp 321ndash326 2002

[21] D Suarez D Zayas and F Guisado ldquoPropolis patents andtechnology trends for health applicationsrdquo Journal of BusinessChemistry vol 2 no 3 pp 119ndash125 2005

[22] ldquoMinisterio do desenvolvimento da industria e comerciordquohttpalicewebmdicgovbr

[23] H Aga T Shibuya T SugimotoM Kurimoto and S NakajimaldquoIsolation and identification of antimicrobial compounds inBrazilian propolisrdquo Bioscience Biotechnology and Biochemistryvol 58 no 5 pp 945ndash946 1994

[24] W Thomson ldquoPropolisrdquo Medical Journal of Australia vol 153article 654 1990

[25] K R Markham K A Mitchell A L Wilkins J A Daldy andY Lu ldquoHPLC and GC-MS identification of the major organicconstituents in New Zealand propolisrdquo Phytochemistry vol 42no 1 pp 205ndash211 1996

[26] V Bankova G Boudourova-Krasteva J M Sforcin et al ldquoPhy-tochemical evidence for the plant origin of Brazilian propolisfrom Sao Paulo staterdquo Zeitschrift fur Naturforschung C vol 54no 5-6 pp 401ndash405 1999

[27] A Kujumgiev I Tsvetkova Y Serkedjieva V Bankova RChristov and S Popov ldquoAntibacterial antifungal and antiviralactivity of propolis of different geographic originrdquo Journal ofEthnopharmacology vol 64 no 3 pp 235ndash240 1999

[28] S Kumazawa T Hamasaka and T Nakayama ldquoAntioxidantactivity of propolis of various geographic originsrdquo Food Chem-istry vol 84 no 3 pp 329ndash339 2004

[29] H Katircioglu and N Mercan ldquoAntimicrobial activity andchemical compositions of Turkish propolis from differentregionsrdquoAfrican Journal of Biotechnology vol 5 no 11 pp 1151ndash1153 2006


[30] V Bankova G Boudourova-Krasteva S Popov J M Sforcinand S R C Funari ldquoSeasonal vatiations of the chemicalcomposition of Brazilian propolisrdquoApidologie vol 29 no 4 pp361ndash367 1998

[31] J M Sforcin E L Novelli and S R C Funari ldquoSeasonal effectof Brazilian propolis on seric biochemical variablesrdquo Journal ofVenomous Animals and Toxins Including Tropical Diseases vol8 pp 244ndash254 2000

[32] S Silici and S Kutluca ldquoChemical composition and antibac-terial activity of propolis collected by three different races ofhoneybees in the same regionrdquo Journal of Ethnopharmacologyvol 99 no 1 pp 69ndash73 2005

[33] M L Castro J A Cury P L Rosalen et al ldquoPropolis do sudestee nordeste do Brasil influencia da sazonalidade na atividadeantibacteriana e composicao fenolicardquo Quımica Nova vol 30pp 1512ndash1521 2007

[34] V S Bankova S L de Castro and M C Marcucci ldquoPropolisrecent advances in chemistry and plant originrdquo Apidologie vol31 no 1 pp 3ndash15 2000

[35] Y Xu L Luo B Chen and Y Fu ldquoRecent development ofchemical components in propolisrdquo Frontiers of Biology in Chinavol 4 no 4 pp 385ndash391 2009

[36] J O Schmidt ldquoChemical composition and applicationrdquo in BeeProductsmdashProperties Applications and Apitherapy A Mizrahiand Y Lensky Eds pp 15ndash26 New York New York NY USA1997

[37] E Crane Beekeping Science Practice and World ResourcesButterworth Heinemann London UK 1988

[38] V Bankova ldquoChemical diversity of propolis and the problem ofstandardizationrdquo Journal of Ethnopharmacology vol 100 no 1-2 pp 114ndash117 2005

[39] R Christov B Trusheva M Popova V Bankova and MBertrand ldquoChemical composition of propolis from Canada itsantiradical activity and plant originrdquo Natural Product Researchvol 19 no 7 pp 673ndash678 2005

[40] B Trusheva M Popova V Bankova et al ldquoBioactive con-stituents of Brazilian red propolisrdquoEvidence-Based Complemen-tary and Alternative Medicine vol 3 no 2 pp 249ndash254 2006

[41] Y K Park M Ikegaki S M Alencar and F F Moura ldquoEval-uation of Brazilian propolis by both physicochemical methodsand biological activityrdquo Honeybee Science vol 21 no 2 pp 85ndash90 2000

[42] S M Alencar T L C Oldoni M L Castro et al ldquoChemicalcomposition and biological activity of a new type of Brazilianpropolis red propolisrdquo Journal of Ethnopharmacology vol 113no 2 pp 278ndash283 2007

[43] J F M da Silva M C de Souza S R Matta M R de Andradeand F V N Vidal ldquoCorrelation analysis between phenoliclevels of Brazilian propolis extracts and their antimicrobial andantioxidant activitiesrdquo Food Chemistry vol 99 no 3 pp 431ndash435 2006

[44] K Salomao P R S Pereira L C Campos et al ldquoBrazil-ian propolis correlation between chemical composition andantimicrobial activityrdquo Evidence-Based Complementary andAlternative Medicine vol 5 no 3 pp 317ndash324 2008

[45] I S R Cabral T L C Oldoni A Prado R M N Bezerra andS M Alencar ldquoComposicao fenolica atividade antibacterianae antioxidante da propolis vermelha brasileirardquo Quımica Novavol 32 no 6 pp 1523ndash1527 2009

[46] E Gregoris and R Stevanato ldquoCorrelations between polyphe-nolic composition and antioxidant activity of Venetian propo-lisrdquo Food andChemical Toxicology vol 48 no 1 pp 76ndash82 2010

[47] A A Righi T R Alves G Negri L M Marques H Breyerand A Salatino ldquoBrazilian red propolis unreported substancesantioxidant and antimicrobial activitiesrdquo Journal of the Scienceof Food and Agriculture vol 91 pp 2363ndash2370 2011

[48] A Ugur and T Arslan ldquoAn in vitro study on antimicrobialactivity of propolis from Mugla Province of Turkeyrdquo Journal ofMedicinal Food vol 7 no 1 pp 90ndash94 2004

[49] L C Paviani C Dariva M C Marcucci and F A CabralldquoSupercritical carbon dioxide selectivity to fractionate phenoliccompounds from the dry ethanolic extract of propolisrdquo Journalof Food Process Engineering vol 33 no 1 pp 15ndash27 2010

[50] V S Bankova S S Popov and N L Marekov ldquoA study onflavonoids of propolisrdquo Journal of Natural Products vol 46 no4 pp 471ndash474 1983

[51] V Bankova A Dyulgerov S Popov andNMarekov ldquoAGCMSstudy of the propolis phenolic constituentsrdquo Zeitschrift furNaturforschung C vol 42 pp 147ndash151 1987

[52] G Boudourova-Krasteva V Bankova J M Sforcin NNikolova and S Popov ldquoPhenolics from Brazilian propolisrdquoZeitschrift fur Naturforschung C vol 52 no 9-10 pp 676ndash6791997

[53] M C Marcucci J Rodriguez F Ferreres and V BankovaldquoChemical composition of Brazilian propolis from Sao Paulostaterdquo Zeitschrift fur Naturforschung C vol 53 no 1-2 pp 117ndash119 1998

[54] S Tazawa T Warashina and T Noro ldquoStudies on the con-stituents of Brazilian propolis IIrdquoChemical and PharmaceuticalBulletin vol 47 no 10 pp 1388ndash1392 1999

[55] S Kumazawa R Ueda T Hamasaka S Fukumoto T Fujimotoand T Nakayama ldquoAntioxidant prenylated flavonoids frompropolis collected in Okinawa Japanrdquo Journal of Agriculturaland Food Chemistry vol 55 no 19 pp 7722ndash7725 2007

[56] M L Castro A M D Nascimento M Ikegaki C M Costa-Neto S M Alencar and P L Rosalen ldquoIdentification of abioactive compound isolated from Brazilian propolis type 6rdquoBioorganic and Medicinal Chemistry vol 17 no 14 pp 5332ndash5335 2009

[57] C Lotti M C Fernandez A L Piccinelli O Cuesta-Rubio IM Hernandez and L Rastrelli ldquoChemical constituents of redMexican propolisrdquo Journal of Agricultural and Food Chemistryvol 58 no 4 pp 2209ndash2213 2010

[58] M P Popova K Graikou I Chinou and V S Bankova ldquoGC-MS profiling of diterpene compounds inMediterranean propo-lis fromGreecerdquo Journal of Agricultural andFoodChemistry vol58 no 5 pp 3167ndash3176 2010

[59] A Petrova M Popova C Kuzmanova et al ldquoNew biologicallyactive compounds from Kenyan propolisrdquo Fitoterapia vol 81no 6 pp 509ndash514 2010

[60] B Trusheva M Popova E B Koendhori I Tsvetkova CNaydenski and V Bankova ldquoIndonesian propolis chemicalcomposition biological activity and botanical originrdquo NaturalProduct Research vol 25 no 6 pp 606ndash613 2011

[61] S A ShaheenMH Zarga I K Nazer RMDarwish andH IAl-Jaber ldquoChemical constituents of Jordanian propolisrdquoNaturalProduct Research vol 25 no 14 pp 1312ndash1318 2011

[62] C Lotti A L Piccineli C Arevalo et al ldquoConstituents ofHondurian propolis with inhibitory effects on Saccharomycescerevisiae multidrug resistance protein Pdr5prdquo Journal of Agri-cultural and Food Chemistry vol 60 no 42 pp 10540ndash105452012

[63] V Bankova R Christov S Popov O Pureb and G BocarildquoVolatile constituents of propolisrdquoZeitschrift furNaturforschungC vol 49 pp 6ndash10 1994


[64] V Bankova R Christov A Kujumgiev M C Marcucci andS Popov ldquoChemical composition and antibacterial activity ofBrazilian propolisrdquo Zeitschrift fur Naturforschung C vol 50 no3-4 pp 167ndash172 1995

[65] E Nagy V Papay G Litkei and Z Dinya ldquoInvestigation of thechemical constituents particularly the flavonoid componentsof propolis and Populi gemma by GCMS methodrdquo Studies inOrganic Chemistry vol 23 pp 223ndash232 1986

[66] S A Popravko and M V Sokolov ldquoPlant sources of propolisrdquoPchelovodstvo vol 2 pp 28ndash29 1980 (Russian)

[67] M C Marcucci and V S Bankova ldquoChemical compositionplant origin and biological activity of Brazilian propolisrdquoCurrent Topics in Phytochemistry vol 2 pp 115ndash123 1999

[68] F A Tomas-Barberan C Garcıa-Vigueira P Vit-Olivier FFerreres and F Tomas-Lorente ldquoPhytochemical evidence forthe botanical origin f tropical propolis from Venezuelardquo Phy-tochemistry vol 34 no 1 pp 191ndash196 1993

[69] O Cuesta-Rubio B A Frontana-Uribe T Ramırez-Apanand J Cardenas ldquoPolyisoprenylated benzophenones in Cubanpropolis biological activity of nemorosonerdquo Zeitschrift furNaturforschung C vol 57 no 3-4 pp 372ndash378 2002

[70] B Trusheva M Popova H Naydenski I Tsvetkova J GRodriguez andV Bankova ldquoNew polyisoprenylated benzophe-nones from Venezuelan propolisrdquo Fitoterapia vol 75 no 7-8pp 683ndash689 2004

[71] Y K Park S M Alencar A R P Scamparini and C L AguiarldquoPropolis produzida no Sul do Brasil Argentina e Uruguaievidencias fitoquımicas de sua origem vegetalrdquo Ciencia Ruralvol 32 no 6 pp 997ndash1003 2002

[72] A H Banskota Y Tezuka I K Adnyana et al ldquoHepatoprotec-tive and anti-Helicobacter pylori activities of constituents fromBrazilian propolisrdquo Phytomedicine vol 8 no 1 pp 16ndash23 2001

[73] T Matsuno Y Matsumoto M Saito and J Mprikawa ldquoAntitu-mor benzopyran derivative of propolisrdquoChemical Abstracts vol126 Article ID 39814j 1997

[74] T Matsuno M Saito Y Matsumoto and J Morikawa ldquoA newbenzo-120574-pyran derivative isolated from propolisrdquo Zeitschrift furNaturforschung C vol 53 no 11-12 pp 1037ndash1039 1998

[75] T Hashimoto H Aga A Tabuchi et al ldquoAnti-Helicobacterpylori compounds in Brazilian propolisrdquoNaturalMedicines vol52 no 6 pp 518ndash520 1998

[76] D Grunberger R Banerjee K Eisinger et al ldquoPreferentialcytotoxicity on tumor cells by caffeic acid phenethyl esterisolated from propolisrdquo Experientia vol 44 no 3 pp 230ndash2321988

[77] O K Mirzoeva and P C Calder ldquoThe effect of propolis and itscomponents on eicosanoid production during the inflamma-tory responserdquo Prostaglandins Leukotrienes and Essential FattyAcids vol 55 no 6 pp 441ndash449 1996

[78] B Konig and J H Dustmann ldquoFortschritte der celler unter-suchungen zur antivirotischen aktivitat von propolisrdquo Apidolo-gie vol 15 pp 228ndash230 1985

[79] V R Villanueva M Barbier M Gonnet and P Lavie ldquoTheflavonoids of propolis Isolation of a new bacteriostatic sub-stance pinocembrin (dihydroxy-5 7 flavanone)rdquo Annales delrsquoInstitut Pasteur vol 118 no 1 pp 84ndash87 1970

[80] J Metzner E M Schneidewind and E Friedrich ldquoOn theeffects of propolis and pinocembrin on blastomycesrdquo Phar-mazie vol 32 no 11 p 730 1977

[81] P Basnet K Matsushige K Hase S Kadota and T NambaldquoFour di-O-caffeoyl quinic acid derivatives from propolisPotent hepatoprotective activity in experimental liver injury

modelsrdquo Biological and Pharmaceutical Bulletin vol 19 no 11pp 1479ndash1484 1996

[82] M Paintz and J Metzner ldquoZur iokalanasthetischen wirkungvon propolis und einigen Inhaltsstoffenrdquo Pharmazie vol 34 pp839ndash841 1979

[83] M Miyakado T Kato N Ohno and T J Mabry ldquoPinocembrinand (+)-120573-eudesmol fromHymenocleamonogyra andBaccharisglutinosardquo Phytochemistry vol 15 no 5 p 846 1976

[84] K Hayashi S Komura N Isaji N Ohishi and K Yagi ldquoIsola-tion of antioxidative compounds from Brazilian propolis 34-dihydroxy-5-prenylcinnamic acid a novel potent antioxidantrdquoChemical and Pharmaceutical Bulletin vol 47 no 11 pp 1521ndash1524 1999

[85] T Kimoto S Koya-Miyata K Hino et al ldquoPulmonary car-cinogenesis induced by ferric nitrilotriacetate in mice andprotection from it by Brazilian propolis and artepillin CrdquoVirchows Archiv vol 438 no 3 pp 259ndash270 2001

[86] Y Akao H Maruyama K Matsumoto et al ldquoCell growthinhibitory effect of cinnamic acid derivatives from propolis onhuman tumor cell linesrdquoBiological and Pharmaceutical Bulletinvol 26 no 7 pp 1057ndash1059 2003

[87] Y K Park I Fukuda H Ashida et al ldquoSuppression ofdioxin mediated aryl hydrocarbon receptor transformation byethanolic extracts of propolisrdquo Bioscience Biotechnology andBiochemistry vol 68 no 4 pp 935ndash938 2004

[88] A Russo V Cardile F Sanchez N Troncoso A Vanella andJ A Garbarino ldquoChilean propolis antioxidant activity andantiproliferative action in human tumor cell linesrdquo Life Sciencesvol 76 no 5 pp 545ndash558 2004

[89] Y Inokuchi M Shimazawa Y Nakajima S Suemori SMishima and H Hara ldquoBrazilian green propolis protectsagainst retinal damage in vitro and in vivordquo Evidence-BasedComplementary and Alternative Medicine vol 3 no 1 pp 71ndash77 2006

[90] H Li A Kapur J X Yang et al ldquoAntiproliferation of humanprostate cancer cells by ethanolic extracts of Brazilian propolisand its botanical originrdquo International Journal of Oncology vol31 no 3 pp 601ndash606 2007

[91] T Shimizu A Hino A Tsutsumi K P YongWWatanabe andM Kurokawa ldquoAnti-influenza virus activity of propolis in vitroand its efficacy against influenza infection in micerdquo AntiviralChemistry and Chemotherapy vol 19 no 1 pp 7ndash13 2008

[92] R M Darwish R J A Fares M H A Zarga and I KNazer ldquoAntibacterial effect of Jordanian propolis and isolatedflavonoids against human pathogenic bacteriardquo African Journalof Biotechnology vol 9 no 36 pp 5966ndash5974 2010

[93] B Kouidhi T Zmantar and A Bakhrouf ldquoAnti-cariogenicand anti-biofilms activity of Tunisian propolis extract and itspotential protective effect against cancer cells proliferationrdquoAnaerobe vol 16 no 6 pp 566ndash571 2010

[94] K W Cheung D M Y Sze W K Chan R X Deng W Tuand G C F Chan ldquoBrazilian green propolis and its constituentartepellin C inhibits allogenic activated human CD4 T cellsexpansion and activationrdquo Journal of Ethnopharmacology vol138 no 2 pp 463ndash471 2011

[95] M J Valente A F Baltazar R Henrique L Estevinho andM Carvalho ldquoBiological activities of Portuguese propolisprotection against free radical-induced erythrocyte damage andinhibition of human renal cancer cell growth in vitrordquo Food andChemical Toxicology vol 49 no 1 pp 86ndash92 2011

[96] J Shvarzbeyn and M Huleihel ldquoEffect of propolis and caffeicacid phenethyl ester (CAPE) on NF120581B activation by HTLV-1Taxrdquo Antiviral Research vol 90 no 3 pp 108ndash115 2011


[97] T Kamiya H Nishihara H Hara and T Adachi ldquoEthanolextract of Brazilian red propolis induces apoptosis in humanbreast cancer MCF-3 cells through endoplasmic reticulumstressrdquo Journal of Agricultural and Food Chemistry vol 60 no44 pp 11065ndash11070 2012

[98] G C Franchi Jr C S Moraes V C Toreti A Daugsch A ENowill and Y K Park ldquoComparison of effects of the ethanolicextracts of Brazilian propolis on human leukemic cells asassessed with the MTT assayrdquo Evidence-Based Complementaryand Alternative Medicine vol 2012 Article ID 918956 6 pages2012

[99] C P Chuu H P Lin M F Ciacco et al ldquoCaffeic acid phenethylester suppresses the proliferation on human prostate cancercells through inhibition of p70S6K andAkt signaling networksrdquoCancer Prevention Research vol 5 no 5 pp 788ndash797 2012

[100] K Yasukawa S Y Yu S TsutsumiM Kurokawa andY K ParkldquoInhibitory effects of Brazilian propolis on tumor promotion intwo-stage mouse skin carcinogenesisrdquo Journal of Pharmacy andNutrition Sciences vol 2 pp 71ndash76 2012

[101] R Zukowska-Markiewicz M H Borawska A FiedorowiczS K Naliwajko D Sawicka and H Car ldquoPropolis changesthe anticancer activity of temozolomide in U87MG humanglioblastoma cell linerdquo Evidence-Based Complementary andAlternative Medicine vol 13 article 50 2013

[102] K Ikeno T Ikeno and C Miyazawa ldquoEffects of propolis ondental caries in ratsrdquo Caries Research vol 25 no 5 pp 347ndash3511991

[103] H Koo P L Rosalen J A Cury Y K Park M Ikegakiand A Sattler ldquoEffect of Apis mellifera propolis from twoBrazilian regions on caries development in desalivated ratsrdquoCaries Research vol 33 no 5 pp 393ndash400 1999

[104] H Koo A M Vacca Smith W H Bowen P L Rosalen J ACury and Y K Park ldquoEffects of Apis mellifera propolis on theactivities of streptococcal glucosyltransferases in solution andadsorbed onto saliva-coated hydroxyapatiterdquo Caries Researchvol 34 no 5 pp 418ndash426 2000

[105] H Koo B P F A Gomes P L Rosalen G M B AmbrosanoY K Park and J A Cury ldquoIn vitro antimicrobial activity ofpropolis and Arnica montana against oral pathogensrdquo Archivesof Oral Biology vol 45 no 2 pp 141ndash148 2000

[106] H Koo J A Cury P L Rosalen G M B Ambrosano MIkegaki and Y K Park ldquoEffect of a mouthrinse containingselected propolis on 3-day dental plaque accumulation andpolysaccharide formationrdquo Caries Research vol 36 no 6 pp445ndash448 2002

[107] H Koo P L Rosalen J A Cury et al ldquoEffect of a new varietyof Apis mellifera propolis on mutans streptococcirdquo CurrentMicrobiology vol 41 no 3 pp 192ndash196 2000

[108] H Koo S K Pearson K Scott-Anne et al ldquoEffects of api-genin and tt-farnesol on glucosyltransferase activity biofilmviability and caries development in ratsrdquoOral Microbiology andImmunology vol 17 no 6 pp 337ndash343 2002

[109] H Koo B Schobel K Scott-Anne et al ldquoApigenin and tt-farnesol with fluoride effects on S mutans biofilms and dentalcariesrdquo Journal of Dental Research vol 84 no 11 pp 1016ndash10202005

[110] M F Hayacibara H Koo P L Rosalen et al ldquoIn vitro and invivo effects of isolated fractions of Brazilian propolis on cariesdevelopmentrdquo Journal of Ethnopharmacology vol 101 no 1ndash3pp 110ndash115 2005

[111] S Duarte P L Rosalen M F Hayacibara et al ldquoThe influenceof a novel propolis on mutans streptococci biofilms and caries

development in ratsrdquo Archives of Oral Biology vol 51 no 1 pp15ndash22 2006

[112] S A D C Duailibe A G Goncalves and F J M Ahid ldquoEffectof a propolis extract on Streptococcus mutans counts in vivordquoJournal of Applied Oral Science vol 15 no 5 pp 420ndash423 2007

[113] M J Kini C S Kini B H Kim et al ldquoAntimicrobial effect ofKorean propolis against the mutans streptococci isolated fromKoreanrdquo Journal of Microbiology vol 49 no 1 pp 161ndash164 2011

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


(a) (b)

Figure 1Apis mellifera collecting propolis ofBaccharis dracunculifolia to production propolis in Brazil (a)Apis mellifera collecting leaf apicesBaccharis dracunculifolia (b) deposition of green propolis cracks in the hive

the carcass of a hive invader which the bees have killed butcannot transport out of the hive The bees cover the invaderwith propolis and wax and the remains are left at the bottomor on one of the walls of the hive [2 19] Figure 1 illustratesthe Apis mellifera collecting resinous material from leaf budsof Baccharis dracunculifolia (a) and the deposition of greenpropolis in the hive (b)

In early records are mentioned substances that cast doubton the use or not of propolis In Genesis (c 1700 BC) tzoriwas taken to Egypt once with honey and its healing prop-erties are noted three times in Jeremiah Twice tzori camefromGilead but it was not balm of Gilead which is producedfrom a tree Commiphora opobalsamum Assis believed thatldquoblack waxrdquo referred to in the Egyptian Ebers papyrus (c 1550BC)may have been propolis He also considered that Hebrewtzori was an early word for propolisThis occured six times inthe Hebrew scriptures and was usually translated as balm orbalsam [19]

Egyptians knew very well the antiputrefactive propertiesof propolis andused it to embalm cadaversGreek andRomanphysicians Aristoteles Dioscorides Pliny and Galen werefamiliar with the medicinal properties of propolis It is notknown what methods were used for harvesting it in theancient world although writers in Greece and Rome werefamiliar with it The Greek Historia Animalium referred to asubstance mitys which was probably propolis as ldquoa cure forbruises and suppurating soresrdquo According to Varro in Romepropolis was used by physicians in making poultices and forthis reason it brings even a higher price than honey on theVia Sacra [19]

The propolis was employed as an antiseptic and cica-trizant in wound treatment and as a mouth disinfectantwith these uses being perpetuated in the Middle Ages andamong Arab physicians Propolis was also recognized byother peoples unrelated to the Old World civilizations Incasemployed propolis as an antipyretic agent and the Londonpharmacopoeias of the seventeenth century listed propolisas an official drug Between the seventeenth and twentiethcenturies the propolis became very popular in Europe onaccount of its antibacterial activity [18]

21 Publications and Patents The first work indexed byChemical Abstracts on propolis was in 1903 and the firstpatent was described in 1904 (USAmdashComposition for treat-ing pins and piano strings) One hundred and nine years afterthe first publication in the Chemical Abstract the number ofpublications on propolis reached 3880 in journal and 2884in patents

Figure 2 shows the number of publications on propolisover the decades data were obtained by searching theChemi-cal AbstractsThe global interest in propolis research presentstwo justifications according to Pereira et al [20] the first topresent diverse biological properties and the second by highadded value the sale price of a bottle in Brazil is about 5 to 10real

The scientific production about propolis by documenttype is the majority about journal and patents as shown inFigure 3

The processed patent documents contain highly valuablelegal economic and technical information hence the resultsobtained from their processing make it possible to obtainhighly valuable information to reach conclusions useful askey elements for the design of RampD technological surveil-lance market studies and marketing strategies [21]

Since the first patentwas filed anduntil today it is possibleto see that there was a considerable increase in the number ofpatents in the last thirty years (Figure 4)

According to profile of patents shown in Figure 5 ChinaJapan and Russia are those that holdmost of the patentsThisfact can be justified by China and Russia being the largestproducers of propolis Today 42 of patents are Chinese(Figure 5) and the first Chinese patent appeared in 1993(on ldquoProcess for productionmouth freshenerrdquo)The Japanesehave 15 of patents and the first appeared in 1988 (aboutldquoDeodorants controlling mouth odorrdquo) The first patent wasobtained in 1968 on Russian ldquoToothpasterdquo and represented12 of patents Brazil deposited its first patent in 1997 onldquoDental gelrdquo Some patents are presented in Table 1

Suarez et al [21] noted the trend of patent applicationsaccording to application area for the period 1972ndash2000and observed a high incidence of products with medicinal








5 5 6 1 19 44 196 393994

01000200030004000500060007000

Num

ber o

f pub

licat

ions

Publication decade

1911

ndash192

0

1921

ndash193

0

1931

ndash194

0

1941

ndash195

0

1951

ndash196

0

1961

ndash197

0

1971

ndash198

0

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

-201

2

Tota

l

3864

1305

6838


4 43 7 63 5 2 5 18268

0500

100015002000250030003500400045005000

Num

ber o

f pub

licat

ions

Document type

Book

Clin

ical

tria

l

Com

men

tary

Con

fere

nce

Diss

erta

tion

Edito

rial

Jour

nal

Lette

r

Pate

nt

Revi

ew

Hist

oric

al

3880

2884




2 1 1 0 0 4 5 20 94

459601

0200400600800

10001200140016001800

Num

ber o

f pat

ents

Publication decade

1911

ndash192

0

1901

ndash191

0

1921

ndash193

0

1931

ndash194

0

1941

ndash195

0

1951

ndash196

0

1961

ndash197

0

1971

ndash198

0

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201

3

1697


436353

334224

747252

3921

79


RomanianGerman


Number of patents

Lang

uage

s

1200

Otherlanguages




8

97

529

152

0

100

200

300

400

500

600

Num

ber o

f pat

ents


1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201


476

177

7729 17 6 1 1 1 10

100

200

300

400

500

Language

Num

ber o

f pat

ents

on p

ropo

lisan

d he

alth

y

Chin

ese

Japa

nese

Kore

an

Russ

ian

Engl

ish

Ger

man

Czec

h

Italia

n

Port

ugue

se

Span

ish




Value(U$S)


2010 51213 4346604 84872011 38845 4537727 116812012 41721 5401643 12947




81

25 22 11 10 9 7 2 2 1 1 1

172

020406080

100120140160180200

Num

ber o

f pat

ents

in d

entis

try

Languages

Chin

ese

Engl

ish

Russ

ian

Kore

an

Ger

man

Japa

nese

Port

ugue

se

Fren

ch

Rom

ania

n

Bulg

aria

n

Mol

davi

an

Turk

ishTo

tal p

aten

tsby

lang

uage

s














[51]





[53]

Not reported


[54]



MexicoChampoton


[57]



[58]

Kenyan propolis


[59]


Table 3 Continued




[60]

















H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH


Chrysin


Saccharin

Galangin

CH=CH-COOH







[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of























5 5 6 1 19 44 196 393994

01000200030004000500060007000

Num

ber o

f pub

licat

ions

Publication decade

1911

ndash192

0

1921

ndash193

0

1931

ndash194

0

1941

ndash195

0

1951

ndash196

0

1961

ndash197

0

1971

ndash198

0

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

-201

2

Tota

l

3864

1305

6838


4 43 7 63 5 2 5 18268

0500

100015002000250030003500400045005000

Num

ber o

f pub

licat

ions

Document type

Book

Clin

ical

tria

l

Com

men

tary

Con

fere

nce

Diss

erta

tion

Edito

rial

Jour

nal

Lette

r

Pate

nt

Revi

ew

Hist

oric

al

3880

2884




2 1 1 0 0 4 5 20 94

459601

0200400600800

10001200140016001800

Num

ber o

f pat

ents

Publication decade

1911

ndash192

0

1901

ndash191

0

1921

ndash193

0

1931

ndash194

0

1941

ndash195

0

1951

ndash196

0

1961

ndash197

0

1971

ndash198

0

1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201

3

1697


436353

334224

747252

3921

79


RomanianGerman


Number of patents

Lang

uage

s

1200

Otherlanguages




8

97

529

152

0

100

200

300

400

500

600

Num

ber o

f pat

ents


1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201


476

177

7729 17 6 1 1 1 10

100

200

300

400

500

Language

Num

ber o

f pat

ents

on p

ropo

lisan

d he

alth

y

Chin

ese

Japa

nese

Kore

an

Russ

ian

Engl

ish

Ger

man

Czec

h

Italia

n

Port

ugue

se

Span

ish




Value(U$S)


2010 51213 4346604 84872011 38845 4537727 116812012 41721 5401643 12947




81

25 22 11 10 9 7 2 2 1 1 1

172

020406080

100120140160180200

Num

ber o

f pat

ents

in d

entis

try

Languages

Chin

ese

Engl

ish

Russ

ian

Kore

an

Ger

man

Japa

nese

Port

ugue

se

Fren

ch

Rom

ania

n

Bulg

aria

n

Mol

davi

an

Turk

ishTo

tal p

aten

tsby

lang

uage

s














[51]





[53]

Not reported


[54]



MexicoChampoton


[57]



[58]

Kenyan propolis


[59]


Table 3 Continued




[60]

















H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH


Chrysin


Saccharin

Galangin

CH=CH-COOH







[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















8

97

529

152

0

100

200

300

400

500

600

Num

ber o

f pat

ents


1981

ndash199

0

1991

ndash200

0

2001

ndash201

0

2011

ndash201


476

177

7729 17 6 1 1 1 10

100

200

300

400

500

Language

Num

ber o

f pat

ents

on p

ropo

lisan

d he

alth

y

Chin

ese

Japa

nese

Kore

an

Russ

ian

Engl

ish

Ger

man

Czec

h

Italia

n

Port

ugue

se

Span

ish




Value(U$S)


2010 51213 4346604 84872011 38845 4537727 116812012 41721 5401643 12947




81

25 22 11 10 9 7 2 2 1 1 1

172

020406080

100120140160180200

Num

ber o

f pat

ents

in d

entis

try

Languages

Chin

ese

Engl

ish

Russ

ian

Kore

an

Ger

man

Japa

nese

Port

ugue

se

Fren

ch

Rom

ania

n

Bulg

aria

n

Mol

davi

an

Turk

ishTo

tal p

aten

tsby

lang

uage

s














[51]





[53]

Not reported


[54]



MexicoChampoton


[57]



[58]

Kenyan propolis


[59]


Table 3 Continued




[60]

















H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH


Chrysin


Saccharin

Galangin

CH=CH-COOH







[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















[51]





[53]

Not reported


[54]



MexicoChampoton


[57]



[58]

Kenyan propolis


[59]


Table 3 Continued




[60]

















H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH


Chrysin


Saccharin

Galangin

CH=CH-COOH







[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table 3 Continued




[60]

















H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH


Chrysin


Saccharin

Galangin

CH=CH-COOH







[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















H

H

O

O

O

O

O

O

O

O

O

O

H

O

O

O

H

HOHO

HOHO

HO

OHOH

OHOH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH


Chrysin


Saccharin

Galangin

CH=CH-COOH







[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















[23 41 73ndash75]



Caffeic acid


[72 78ndash80]


Pinocembrin


[79 80 82 83]


Quercetin


[41 78]














[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















[88]











In vitro [105]










5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















5 Conclusions



References




























































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of














































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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