Journal of Pharmacy And Bioallied Sciences

: 2011  |  Volume : 3  |  Issue : 4  |  Page : 479--495

Is propolis safe as an alternative medicine?

Maria Graša Miguel1, Maria Dulce Antunes2,  
1 Faculty of Sciences and Technology, Department of Chemistry and Pharmacy, University of Algarve, IBB, Center for Plant Biotechnology, Building 8, Campus de Gambelas, 8005-139 Faro, Portugal
2 Faculty of Sciences and Technology, Department of Biological Sciences and Bioengineering, University of Algarve, IBB, Center for Plant Biotechnology, Building 8, Campus de Gambelas, 8005-139 Faro, Portugal

Correspondence Address:
Maria Graša Miguel
Faculty of Sciences and Technology, Department of Chemistry and Pharmacy, University of Algarve, IBB, Center for Plant Biotechnology, Building 8, Campus de Gambelas, 8005-139 Faro


Propolis is a resinous substance produced by honeybees as defense against intruders. It has relevant therapeutic properties that have been used since ancient times. Nowadays, propolis is of increasing importance as a therapeutic, alone or included in many medicines and homeopathic products or in cosmetics. Propolis is produced worldwide and honeybees use the flora surrounding their beehives for its production. Therefore its chemical composition may change according to the flora. The phenolic and volatile fractions of propolis have been revised in the present study, as well as some of the biological properties attributed to this natural product. An alert is given about the need to standardize this product, with quality control. This has already been initiated by some authors, mainly in the propolis from the poplar-type. Only this product can constitute a good complementary and alternative medicine under internationally acceptable quality control.

How to cite this article:
Miguel MG, Antunes MD. Is propolis safe as an alternative medicine?.J Pharm Bioall Sci 2011;3:479-495

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Miguel MG, Antunes MD. Is propolis safe as an alternative medicine?. J Pharm Bioall Sci [serial online] 2011 [cited 2019 Nov 13 ];3:479-495
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Propolis or bee glue (CAS number 9009-62-5) is a generic name for a resinous substance obtained from beehives, used traditionally as an antimicrobial. It is a heterogeneous mixture of many substances collected, transformed, and used by bees to seal holes in their honeycombs, smooth out the internal walls, and protect the entrance against intruders. [1] In fact, propolis means 'defense of the city'. The word propolis is derived from the Greek words 'pro' (meaning 'in front of"), and 'polis' (meaning 'the city'). In this manner, propolis might serve as a means for colonies to better maintain homeostasis of the nest environment through the reduction of microbial growth on hive walls, prevention of uncontrolled airflow into the nest, waterproofing of walls against external moisture, and protection against invaders. [2] Therefore, propolis could simply mean defense of the hive. [3] However, more recently, some studies have revealed that propolis in honey bee colonies may play a more subtle role in colony level immunity than direct defense against parasites and pathogens. [2]

Bees make use of the mechanical properties of propolis and of its biological action. This action against microorganisms has also been used by human beings since ancient times. [4] Nevertheless, other biological properties have been attributed to this natural product: hepatoprotective, antitumor, antioxidative, and anti-inflammatory. [1],[5],[6],[7],[8] In fact, propolis, along with other honeybee products such as honey, royal jelly, and pollen, have relevant therapeutic properties, being used since 300 years B.C. in folk medicine worldwide. [9] Research regarding the chemical composition of propolis of diverse origins, their pharmacological properties, and relation between its composition and biological activities has increased in the last few years. [10] This product has, therefore, gained popularity as an alternative medicine for health amelioration and disease prevention. [11] Some examples include its utilization for increasing the body's natural resistance to infections and lowering blood pressure and cholesterol levels. It has been also used in mouthwash products and toothpastes to prevent caries and treat gingivitis and stomatitis, [12] in cough syrups, oral pills, lozenges, ointments, lotions, and vitamins. [13] Holistic therapists often use propolis for the relief of some inflammations, viral diseases, fungal infections, ulcers, and superficial burns along with acupuncture, ayurveda, and homeopathy. [13]

Among the chemical substances found in propolis are waxes, resins, balsams, aromatic and ethereal oils, pollen, and other organic matter. [14] Typically propolis is comprised of resin (50%), which is composed of flavonoids and related phenolic acids, generally called as the polyphenolic fraction, waxes (30%), essential oil (10%), pollen (5%), and other organic compounds (5%). [15],[16] However, this chemical composition may change according to the plant source, which is related to the regional vegetation and to the season in which it is collected by the bees. [17] Therefore, the standardization of this product is difficult on account of the inherent difficulties associated with the analysis of complex mixtures from different vegetal sources. [18]

The present study is focused on the chemical variability of the phenols and volatiles of propolis and its repercussion in the biological activities.

 Chemical Variability of the Phenols

Propolis cannot be used as a crude material. It must be purified by extraction with adequate solvents, to remove the unwanted material, preserving the active components, for example, the polyphenolic fractions. Several solvents have been used such as water, ethanol, methanol, hexane, acetone, and chloroform, with ethanol being the most common, particularly at concentration of 70%. [12],[19]

The compounds present in the propolis resin have three origins: substances actively secreted by plants and substances exuded from wounds in plants (lipophilic materials on leaves and leaf buds, resins, mucilage, gums, lattices, among others) collected by bees, secreted substances from bee metabolism, and materials which are introduced during propolis elaboration. [10],[20] As such compounds have a plant origin, the composition of the plant source determines the chemical composition of propolis.

The chemical composition of propolis depends on the local floral at the site of collection, being therefore, highly variable. [4],[10]

In spite of this diversity and according to the most studied propolis types, Bankova [20] cited at least six main chemical types of propolis: (1) Poplar propolis found in Europe, North America, and the non-tropical regions of Asia, for which the plant source is Populus spp. of section Aigeiros, most often P. nigra. (2) Birch propolis from Russia, for which the plant source is Betula verrucosa Ehrh.; (3) Green propolis from Brazil, mainly from Baccharis spp., predominantly B. dracunculifolia DC.; (4) Red propolis from Cuba and Venezuela, from Clusia spp.; (5) 'Pacific' propolis from Okinawa and Taiwan, for which the plant source is unidentified yet; and (6) 'Canarian' propolis from Canary Islands, for which the plant source is also unknown [Table 1].{Table 1}

The main biologically active substances in these types of propolis are different. Flavones, flavanones, phenolic acids, and their esters predominate in the poplar propolis [Figure 1], while flavones and flavonols dominate in the birch propolis [Figure 2].{Figure 1}{Figure 2}

In green and red propolis, prenylated p-coumaric acids, diterpenic acids [Figure 3], and polyprenylated benzophenones [Figure 4] dominate. C-prenylflavanones [Figure 5] and furofuran lignans [Figure 6] predominate in the 'Pacific' and 'Canarian' propolis, respectively. [20] However, particularly due to the richness of the flora in some countries, different types of propolis have been reported for the same region.{Figure 3}{Figure 4}{Figure 5}{Figure 6}

 Propolis from Europe, China, and North America

In Europe, China, and North America, propolis is generally considered to be of the poplar-type; nevertheless, several authors have demonstrated that other types can be found, owing to the flora specificity of each region. In Europe, the Mediterranean propolis from diverse places in Greece contains mainly diterpenes and almost no phenolics. [21] Such a profile has been described for propolis from Sicily and northwestern Greece, [22],[23] and can also be found in Croatia and Malta [Table 2] and [Figure 7]. [21],[22],[23],[24]{Table 2}{Figure 7}

The botanical origin of diterpenes in the propolis samples from Greece is yet unidentified, but on the basis of the diterpenic profile, the source plant should be the conifer species of the Cupressaceae family, in which the flora of the region is very rich. [21] In addition, in Malta, there are other propolis samples also, wherein another compound group is observed: mono- and sesquiterpenyl esters of substituted benzoic acids [Table 2] and [Figure 8], [24] which are attributed to a genus Ferula plant found in this region. Mono- and sesquiterpene esters of benzoic acids have also been found in propolis samples from Iran, along with others in which flavonoids and caffeate ester compounds predominate. [25],[26] Such results may be due to the simultaneous presence of Populus spp. and Ferula spp.{Figure 8}

In another study, Kalogeropoulos et al., [27] also reported that the Greek (mainland Greece and Greek islands) and east Cypriot propolis samples shared characteristics that were different from typical European propolis, because those samples presented anthraquinones (mainly emodin and chrysophanol) [Table 2] and [Figure 9] and terpenes and/or flavonoids in significant amounts, and had low abundance of phenolic acids and their esters.{Figure 9}

In Cretan propolis, five new terpenes were isolated: the diterpenes 14,15-di(nor)-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 [Table 2] and [Figure 10]. [28] These cycloartane triterpenes were isolated only from Brazilian propolis (tropical type), Mangifera indica (Anacardiaceae) being the plant source [Table 3] and [Figure 11]. [29]{Table 3} {Figure 10}{Figure 11}

The main sources of phenolic compounds found in Turkish propolis were the poplar bud exudates. Nevertheless some authors were able to classify the samples collected in different regions of Turkey in four main groups: the typical poplar samples from Central and Western Anatolia; a sample from Adana (Central Anatolia), in which the poplar type compounds were present in lower amounts, the main ones being cinnamyl cinnamate and diterpenic acids (dihydroabietic, abietic, and isopimaric); a sample from Eastern Anatolia that presented significant amounts of hydroxyl fatty acids (hydroxypalmitic, hydroxystearic) and triterpenoid alcohols besides the poplar phenolics in lower amounts; and finally, also from Eastern Anatolia, a sample with low concentrations of flavonoids and very high levels of p-coumaric and ferulic acids, as well as a series of phenolic glycerides. [30]

In recent times, some authors found in the propolis samples from North Portugal, phenolic acids and their esterified and / or methylated derivatives, as well as dihydroflavonols, flavones, flavanones and flavonols, either as free from or with methylated/esterified forms, similar to those of the European-type. Nevertheless, new compounds could also be found: methylated and/or esterified or hydroxylated derivatives of common poplar flavonoids as well as a p-coumaric ester derivative dimmer [Table 4] and [Figure 12]. [31]{Table 4}{Figure 12}

With regard to China, the propolis of this region is also of the poplar-type [Table 5] and [Figure 13]. [20],[32],[33],[34],[35] However in the Chinese propolis some authors also have described some new compounds that had not yet been referred [Table 5] and [Figure 14]. [33],[35] Continuing in the Asian Continent, propolis samples from Myanmar have cycloartane-type triterpenoids and prenylated flavanones, practically dissimilar from those of its neighboring China. [36]{Table 5}{Figure 13}{Figure 14}

In Korea, studies performed by some authors allowed to classify the propolis from several places of this country into poplar-types, such as those of Europe and China. [37] Also, for the first time in Jeju, a southern island of Korea with a subtropical climate, a new chalcone 4'-methoxy-bavachromanol as well as new khellactone derivatives (laserpitin and isolaserpitin) were found [Table 6] and [Figure 15]. [38]{Table 6}{Figure 15}

In the same continent, and for the first time, open-chain neoflavonoids were identified in propolis samples from Nepal, as also new chalcone, flavanone, flavan-3-ol, isoflavonoids, and flavanonol compounds [Table 7] and [Figure 16]. [39],[40],[41]{Table 7}{Figure 16}

Bud exudates of poplar trees are the main source of propolis in the temperate zones and chemical data show a clear preference for the Populus species belonging to the section Aigeiros, as is seen in Europe and North America. [42] In fact, in North America, mainly in the propolis from Ontario (Canada), most studies demonstrate that propolis also originates from the Populus section Aigeiros. Nevertheless, the compounds found in the propolis from Canada in which Aigeiros poplars are absent (Boreal forest and Pacific Coastal forest regions), are different: in Victoria, the components found in propolis are dihydrochalcones, considered to be characteristic of bud exudates of poplars from Populus section Tacamahaca and in the Richmond region, are found large amounts of p-coumaric and cinnamic acids, typical of poplars of section Leuce. [43]

However, in South America, concretely the Uruguayan propolis components were similar to those from Europe and China, suggesting that there is a similar plant origin in the Uruguayan propolis also. [44]

 Propolis from Russia

Significant amounts of phenolic glycerides such as dicoumaroyl acetyl glycerol, diferuloyl acetyl glycerol, feruloyl coumaroyl acetyl glycerol, and caffeoyl coumaroyl acetyl glycerol have been isolated from the propolis obtained in Northern Russia. [42] These compounds are attributed to Populus tremula, in which the exudates are rich in such components. Birch propolis (Betula verrucosa Ehrh) predominates in Russia and its main biologically active substances are flavones and flavonols, other than those reported for European propolis. [20],[42],[45]

 Propolis from Brazil

The Brazilian propolis represents 10 - 15% of the worldwide production, Brazil being the third world producer, behind Russia and China. [46] Among the types produced in Brazil, green propolis (from greenish-yellow to deep green) prevails, gaining preference in the world propolis market. [47] Prenylated derivatives of p-coumaric, artepillin C (4-hydroxy-3,5-diprenyl cinnamic acid), dupranin (4-hydroxy-3-prenyl cinnamic acid), (E)-3-prenyl-4-(dihydroxicinnamoyloxy)-cinnamic acid, and diterpenic acids were detected in green propolis as well as in the buds of Baccharis dracunculifolia, an Asteraceae family from southeast and western-central Brazil. [11],[18],[47],[48]

Nevertheless, other types of Brazilian propolis have been reported. For example, a new type of red propolis, in which isoflavonoids [49],[50] instead of prenylated p-coumaric acids predominated has been reported. [51],[52],[53] The red propolis is mainly collected in north east Brazil where Baccharis spp are practically absent, in this case, Dalbergia ecastophyllum (L.) Taub. (Leguminosae) is the main source of isoflavonoids. [49],[50] Flavonoids, flavonol, isoflavones, isoflavanones, isoflavans, chalcones, auronol, pterocarpans, 2-arylbenzofuran, neoflavonoids, and lignans in the red propolis from Brazil have also been referred by Awale et al. to possess cytotoxic activities [Table 3] and [Figure 17]. [54]{Figure 17}

 Red propolis from Cuba and Venezuela

Red propolis from Cuba was reported to be particularly rich in polyprenylated benzophenones (propolone A, nemorosone, guttiferone, E, xanthochymol, propolones B-D, garcinielliptone I, and hyperibone), due to the presence of Clusia spp. [55],[56],[57],[58] Nevertheless, the chemical composition of other propolis samples from the same country did not present prenylated benzophenones. In the samples from Pinar del Rio province, isoflavonoids predominated. [59] Of late, some authors classified the Cuban propolis into three types: (1) Brown Cuban propolis mainly comprised of polyisoprenylated benzophenone derivatives; (2) Red Cuban propolis, characterized by the presence of isoflavonoids; and (3) Yellow Cuban propolis, in which 1 H- and 13 C-NMR spectral data suggested the presence of aliphatic compounds (terpenoids and sterols) as the main constituents, but these compounds were not identified. [60] Only recently, and by GC-MS, the yellow Cuban propolis, collected from different regions of Cuba, was classified into two main types: type A, rich in triterpenic alcohols [Table 8] and [Figure 18] with polymethoxylated flavonoids [Table 8] and [Figure 19] as minor compounds, and type B, containing acetyl triterpenes as the main constituents. [61] According to these authors the botanical sources of the two types of yellow Cuban propolis were not yet identified.{Table 8}{Figure 18}{Figure 19}

Some authors suggested that Clusia minor and C. major (Guttiferae) were the source of the main phenolics present in the propolis from Venezuela. Their resins exuded polyprenylated benzophenones as found in propolis. Only few samples presented flavonoids and in each case they were found to be lipophilic methylated 6-oxygenated flavones (eupatorin, hispidulin, among others). [62] Later on, Trusheva et al. [63] found two new polyisoprenylated benzophenones: 18-ethyloxy-17-hydroxy-17,18-dihydroscrobiculatone A and 18-ethyloxy-17-hydroxy-17,18-dihydroscrobiculatone B, together with the known scrobiculatones A and B, in the propolis samples from Venezuela [Table 9] and [Figure 4] and [Figure 20]. These polyisoprenylated benzophenones were only found in the floral resin of C. scrobiculata. According to the authors, this plant material was used by honeybees as a source for propolis, in the tropical rain forest of the Truhillo state in Venezuela.{Table 9}{Figure 20}

In the red-type Mexican propolis, samples of flavanones, isoflavans, and pterocarpans were found to be in agreement with the chemical profiles of the Cuban and Brazilian red propolis, but three new isoflavonoids were also found along with the presence of compounds with a 1,3-diaryl-propane and 1,3-diaryl propene carbon skeleton, which was related to the presence of Dalbergia genus [Table 10] and [Figure 21]. [64]{Table 10}{Figure 21}

 'Pacific' propolis from Okinawa and Taiwan

In the 'Pacific' propolis from Okinawa and Taiwan, the structures of two prenylflavanones were elucidated by the NMR spectral technique in the Taiwanese propolis. They were reported for the first time and called propolins. [65] Further studies allowed the finding of other similar structures within the propolin group in the Taiwanese propolis, whose concentrations were closely dependent on the locations and collection seasons [Table 11] and [Figure 5]. [66],[67] These propolins (prenylated flavonoids) had Macaranga tanarius as the plant source. [68]{Table 11}

Fujimoto et al., [69] analyzing several propolis samples from all over the world, considered that samples from Japan were similar to the European and Chinese ones (European-type). However, in some places in Japan, some variability was reported. [70],[71] These authors considered such diversity was due to the great diversity of climate and vegetation in the islands of Japan, which extended from north (Hokkaido) to south (Okinawa). This place was located in the subtropical zone and the vegetation was quite different from the other areas. [70] Studies conducted by some authors [72] revealed that not all propolis from the Okayama Prefecture (central Japan) considered as 'poplar type' were effectively of this type. Propolis from Takebe-cho had constituents not present in the propolis of other places of the same Prefecture. Such results were attributed to a plant grown mainly in this region (Rhus javanica var. chinensis).

In the Southern Hemisphere, the chemical composition of propolis from different regions in Java were also evaluated. [73] The authors found some variability of constituents in the samples of propolis from three different places, in spite of that, all of them contained phenolic acids. The samples from Batany showed the presence of aromatic acids groups, terpenes, and 3,4-dimethylthioquinoline and 3-quinolinecarboxamine, two new compounds. In the Lawang sample, high amounts of aromatic acids were found and three new compounds were also reported (4-oxo-2-thioxo-3-thiazolidinepropionic acid, glucofuranuronic acid, and patchoulene). In the Sukabumi propolis sample, only very low amounts of aromatic acids were found and silanol was reported for the first time. The presence of this compound in the propolis samples was explained by the presence of rubber plants in that area and the extract latex product from the Hevea rubber plants was polydimathylsiloxane elastomer. [73]

 'Canarian' Propolis from Canary Islands

Only one study was found about the chemical composition of the propolis from Canary Islands. The authors who studied the samples of this region detected that they were significantly different from the remaining ones studied so far in the world. Lignans [Table 12] and [Figure 6], mainly of the furofuran type, and carbohydrates (pentoses, hexoses, and dissacharide) were found to be the main components. [74] According to the authors, two plant species could be responsible for that composition: one of them would produce resinous exudates rich in lignans of the furofuran type and a second plant source from which most sugars were used by honeybees for creating propolis.{Table 12}

 Volatile Compounds

Very few studies on the volatile fraction of worldwide propolis were found. This was not surprising, as essential oils constituted generally 10% of the samples against 50% of the resinous substances.

Volatile compounds are in fact found in low concentrations in propolis, but their aroma and biological activity make them significant for the characterization of propolis. [4] Mono- and sesquiterpenoids constitute the most important group of compounds found in propolis samples from diverse regions of Europe. Prenylated acetophenones can also be found in some samples from Brazil. [4] Similar to reports on the extracts, the volatile chemical composition of propolis is also dependent on the flora. Some authors have reported that the volatile composition of propolis is also dependent on the bee species, because Apis mellifera and Melipona beechei in the same region of Yucatαn (Mexico) have produced propolis with different volatile compositions. [75],[76] The same has occurred in Turkey where phenols and terpenes present in the propolis samples depend on the race of honeybees. [77]

There are variations in the chemical composition of the volatile fraction of propolis from the temperate and tropical zones. Although propolis from the temperate climate zones is generally classified into two types: eudesmol and benzyl benzoate, in the tropical zones there is great chemical variability. [76] However, propolis collected at five different locations in Greece revealed a predominance of a-pinene, except in samples from one location, in which junipene existed. The presence of junipene along with trans-b-terpineol, manool or manoyl oxide in these samples was reported for the first time as a propolis constituent. [78] However, in Europe, -pinene does not predominate in the volatile fraction of propolis. For example, the major volatile components of Dalmatian (Croatia) propolis were benzyl alcohol, benzoic acid, and benzyl benzoate (49%), along with terpenes (30%). In the Canary Islands, the main components appeared to be terpenoids, mainly sesquiterpene hydrocarbons and alcohols. Spathulenol was the major sesquiterpene in the Canary Island samples, and benzoyl benzoate was also found. [74]

With regard to terpenoids obtained by extraction with 70% ethanol, it was found that propolis from Anatolia (Turkey) had a-cedrol, b-eudesmol, a-eudesmol, -bisabolol, b-caryophyllene, d-cadinene, caryophyllene oxide, b-selinene, a-cadinol, aromadendrene 2, and germacrene A. These compounds were not present in all samples, but depended on the region from where they were collected. [79]

The volatile components of 23 propolis samples from 17 provinces of China were analyzed by dynamic headspace sampling, with gas chromatography and mass spectrometry. [80] The major components were a-cedrene, g-eudesmol, 3-methyl-3-buten-l-ol, g-terpineol, acetic acid, benzyldehyde, benzyl alcohol, cedrol, butanoic acid, ethyl ester, g-cadinene, phenylethyl alcohol, and styrene. Acetic acid was already found in higher content in other Chinese propolis. [81] Luo et al. [80] suggested that the volatile chemical composition detected in the propolis samples could be related to different climates and plant origins.

Several studies concerning the essential oils isolated from Brazilian propolis were found, and they demonstrated the diversity of the chemical composition. The essential oil isolated from the green propolis of Minas Gerais was for the first time studied and the authors reported that (E)-nerolidol, b-caryophyllene, and selina-3,7(11-diene) constituted the most important components of the essential oil of propolis. [82] Green propolis collected in southeastern Brazil, was mainly composed of nerolidol, a-pinene, 1-phenyl-ethanone, linalool, trans-caryophyllene, d-cadinene, Spathulenol, and globulol. [83] Generally all the compounds were also present in the essential oil of Baccharis dracunculifolia.

The red propolis from Maceio city, Alagoas State, had trans-anethole, methyl eugenol, trans-methylisoeugenol, elemicin, and trans-isoelemicin. These components were partially responsible for the unusual anis-like odor of this red propolis. [84]

Red propolis from Goiana, Pernambuco State, had major volatile components like trans-anethole, a-copaene, and methyl cis-isoeugenol. The authors observed also that some compounds could be present or absent according to the collection season, although trans-anethole was always the major one. [85] Also, in October they found, d-cadinol, b-gurjunene, isocaryophyllene, and d-cadinene, which were absent in the remaining collection seasons, whereas, in June, 1,8-cineole and a-selinene were the main components found, in contrast to the remaining collection seasons.

Nerolidol, spathuelenol, aliphatic hydrocarbons, and alkylbenzenes and alkylnaphtalenes constituted the major components or the group of components present in samples of propolis from Piaui State and Parana State (Brazil). [86] Kusumoto et al., [87] found in the Brazilian essential oils of propolis from the virgin forests of Alecrim, in the Southern part of Minas Gerais State, the following components: 2,2-dimethyl-8-prenyl-6-vinylchromene and 2,6-diprenyl-4-vinylphenol (two new compounds), along with 2,2-dimethyl-6-vinylchromene, acetophenone, 2-prenyl-4-vinylphenol, 3,4-dimethoxy-styrene, 3,4-dimethoxy-allylbenzene, 4-hydroxy-3,5-diprenylbenzaldehyde, and (-)-spathulenol.

These findings show the variability of the chemical composition of the volatile fraction of propolis. Another example is that in which propolis from five different places of Brazil is shown to be qualitatively diverse: 1,8-cineole, exo-fenchol, terpin-4-ol, and fenchone (Teresina); a-pinene, caryophyllene oxide, a-pinene, and a-copaene (Pio IX); (E)-caryophyllene, a-copaene, a-pinene, caryophyllene oxide, and a-cadinene (Campo Maior); (E)-caryophyllene, a-gurjunene, and a-selinene (Pedro II); and (E)-caryophyllene, a-gurjunene, a-cadinene, and a-copaene (Lagoa de Sao Francisco). All these places belong to the Piaui State. [76] More examples can be found, the most abundant components of propolis from Rio de Janeiro collected in July were: b-caryophyllene, acetophenone, linalool, g-elemene, g-cadinene, and g-muurolene. [88]

 Biological Properties of Propolis

Despite the great chemical variability of propolis, there are hundreds of studies dealing with the biological activity of propolis, sometimes from different origins, but with similar properties. [89],[90],[91],[92],[93],[94],[95],[96],[97],[98],[99],[100],[10],[102],[103],[104,[105],[106],[107],[108],[109],[110],[111],[112],[113],[114],[115],[116],[117],[118],[119],[120],[121],[122],[123],[124],[125],[126],[127],[128],[129],[130],[131],[132],[133],[-134]

The distinct chemistry of propolis from diverse origins sometimes does not mean dissimilar properties. [20] Propolis, being a defense system of bees against infections, they have to find components that possess such properties. Bees can find them in the flora that surrounds their beehives. In Europe, such compounds include flavanones, flavones, phenolic acids, and their esters from poplars, whereas in Brazil the anti-infectious compounds are prenylated p-coumaric acids and diterpenes from B. dracunculifolia or prenylflavanones from 'Pacific' propolis. [20],[115]

Some authors [135] compared the antibacterial activity of three groups of propolis: European, Brazilian, and Central American. Propolis from Brazil and Europe possessed similar activities despite the dissimilarity in the composition, and the propolis from Central America had lower antibacterial activity. In the same study, no significant correlation was found between geographic origin and potential cytotoxicity.

However, it is also true that different components can give diverse antimicrobial properties. Seidel et al. [101] comparing the antibacterial activity of propolis from different geographical origins, including countries from tropical, subtropical, and temperate zones, found that propolis extracts were mostly active against Gram positive bacteria. They also observed that propolis from the wet-tropical, rainforest-type climate had the highest antibacterial activity. [101] The methodology used was the same for all analyses (broth microdilution assay). Other studies demonstrated that propolis from Brazil, Peru, The Netherlands, and China, generally possessed hepatoprotective activity and scavenging activity against DPPH free radicals, whereas, those from China and The Netherlands had the strongest cytotoxic activity. [136]

In vitro antioxidant activity (b-carotene bleaching test and DPPH free radical scavenging assays) of the ethanol extracts of propolis from diverse regions (Argentina, Austria, Brazil, Bulgaria, Chile, China, Hungary, New Zealand, South Africa, Thailand, Ukraine, Uruguay, the USA, and Uzbekistan) was evaluated by Kumazawa et al. [137] and compared with the chemical composition. This was performed by HPLC analysis with photo-diode array (PDA) and mass spectrometry (MS). The most active propolis was that obtained from Argentina, Australia, China, Hungary, and New Zealand, which also possessed the highest total polyphenol and flavonoid contents. The activity correlated well with the levels of kaempferol and phenethyl caffeate present in these samples of propolis. Practically the same compounds were present in the propolis obtained from various places in China (caffeic acid, ferulic acid, and caffeic acid phenethyl ester), presenting in all of them a strong antioxidant activity. [35] Similar results were observed in the propolis from different locations of Korea, which means, samples with high amounts of caffeic acid, kaempferol, and phenethyl caffeate possessed the best antioxidant activity, in contrast to a sample from a more distant place, in which the levels of those components were lower. [37] Some authors, [70] reported a relationship between high phenolic content and antioxidant activity in the propolis from different zones of Japan. The samples with the best activities were those from Akita (Minamiakita) and Okinawa. However, the constituents of the phenolic fraction were different. In fact, in the samples from Akita, caffeic acid and phenethyl caffeate were predominant. In Okinava, the antioxidant activity was due to the prenylated flavonoids. Kumazawa et al. [138] showed that the position of the geranyl or prenyl groups on the flavonoid skeleton played an important role on the antioxidant activity. Also Chen et al. [66] reported that some propolins had better activity than the others.

Both propolis from Europe and Brazil, with diverse chemical compositions, possessed anti-inflammatory activities. In both cases the mechanism was due to the inhibition of NO production. [108],[139] The open-chained neoflavonoids from Nepal, also had the capacity for inhibiting NO production, mainly those having a ketone carbonyl at C-1 in ring A, instead of those having a methoxyl substituent. [39]

The caffeic acid phenethyl ester and its related polyphenolic acid esters elicited an important effect on erythrocyte membrane lipid peroxidation, cellular strand breakage, and protein fragmentation. According to these results, the authors considered that caffeic acid phenethyl ester could be used as a template for designing novel drugs to combat diseases induced by oxidative stress components, such as, diverse types of cancer. [140] Propolis from Brazil, China, Peru, and The Netherlands also possessed strong cytotoxicity toward murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cells, although those from The Netherlands and China possessed the strongest cytotoxicity toward murine colon 26-L5 carcinoma cells, which may because these samples had the highest presence of phenolic compounds. [136]

Despite the chemical difference among the three types of propolis studied by Messerli et al., [132] the caffeic acid phenethyl ester-based propolis in Europe, Far East, and New Zealand, the artepillin C-based Brazilian green propolis, and the Brazilian red propolis, they found that all of them possessed anticancer activity. They blocked selective oncogenic PAK1 signaling and suppressed the growth of neurofibromatosis tumors in mice.


Propolis is a heterogeneous product constituted by several groups of compounds. Moreover, the chemical composition depends strongly on the phytogeographic characteristics of the collection site, as honey bees can only use the plant species existing in their habitats. Their chemical variability can give rise to diverse types of biological activities or diverse structures may present similar properties. Therefore, to make a standardization and quality control of this product is very difficult, particularly if we take into account the quantification of the active substances. Popova et al. [67] have proposed to specify multiple standards for different propolis types according to their plant source and corresponding chemical profile. Popova et al. [141] has already made a standardization for the poplar-type propolis from Europe, Asia, and Americas. More recently, Popova et al. [67] have validated a spectrophotometric method for the quantification of prenylated flavanones in the 'Pacific' propolis from Taiwan. In addition, it is necessary to connect a particular chemical propolis type to a specific type of biological activity for formulating recommendations for the practitioners. Only by following this scheme will it be possible for people to choose and make more efficient use of the beneficial properties of propolis, in respect to complementary and alternative medicine. [142]

In spite of propolis being commonly used in cosmetic and medicinal preparations owing to its antiseptic, anti-inflammatory, and anesthesic properties, it is not completely innocuous because 1.2 to 6.6 patients who were patch-tested for dermatitis were sensitive to propolis. The main allergens were 3-methyl-2-butenyl caffeate and phenylethyl caffeate, that is, components present in the poplar-type propolis. [143] Clinical allergy in humans is presented as contact dermatitis or oral mucositis, beekeepers being the most affected. Nevertheless there has been a recent rise in this incidence among biocosmetic users, on account of the increasing popularity of natural products such as propolis. [144] According to these authors, patients with an allergy to propolis may be at risk of cross-sensitization with balsam of Peru, a common allergen found in flavoring agents, perfumed products, certain spices, and products that contain the peel of citrus fruit.

Therefore, propolis is a complex natural product with a great diversity of chemical structures and subsequent biological activities, nevertheless, it is not completely innocuous and care must been taken, mainly when such a product has a great diversity of origins. An absence of quality control may be pernicious to human health.


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