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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 697390, 13 pages
http://dx.doi.org/10.1155/2013/697390
Review Article

Recent Progress of Propolis for Its Biological and Chemical Compositions and Its Botanical Origin

Department of Food Science, College of Food Engineering, State University of Campinas, Monteiro Lobato Street n.80, P.O. Box 6177, 13083-862 Campinas, SP, Brazil

Received 25 January 2013; Accepted 12 March 2013

Academic Editor: Ewelina Szliszka

Copyright © 2013 Viviane Cristina Toreti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Propolis is the generic name given to the product obtained from resinous substances, which is gummy and balsamic and which is collected by bees from flowers, buds, and exudates of plants. It is a popular folk medicine possessing a broad spectrum of biological activities. These biological properties are related to its chemical composition and more specifically to the phenolic compounds that vary in their structure and concentration depending on the region of production, availability of sources to collect plant resins, genetic variability of the queen bee, the technique used for production, and the season in which propolis is produced. Many scientific articles are published every year in different international journal, and several groups of researchers have focused their attention on the chemical compounds and biological activity of propolis. This paper presents a review on the publications on propolis and patents of applications and biological constituents of propolis.

1. Introduction

Propolis is a resinous substance collected by Apis mellifera from various tree buds which they then use to coat hive 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 have been reported including cytotoxic, antiherpes, free radical scavenging, antimicrobial, and anti-HIV activities [39]. Because of the wide range of biological activities, propolis has recently been extensively used in food and beverages to improve health and prevent diseases [1012].

The medical application of propolis preparation has led to an increased interest in its chemical compositions and its botanical origins, because so far mainly polyphenol compounds have been identified in propolis collected by Apis mellifera. The flavonoids, the main polyphenols in propolis, have been found to be quantitatively or qualitatively variable, depending on the environmental plant ecology [1316].

2. History of Propolis and the Research on Propolis

The word “propolis” is derived from the Greek pro (for “in front of” or “at the entrance to”) and polis (“community” or “city”) and means a substance in defense of the hive. Propolis, or bee glue, is a brownish resinous material collected by worker bees from the leaf buds of numerous tree species like birch, poplar, pine, alder, willow, palm, Baccharis dracunculifolia, and Dalbergia ecastaphyllum [15, 17, 18]. In order to manufacture propolis, bees may also use material actively secreted by plants or exuded from wounds in plants [18].

Propolis has been used by man since early times for various purposes as an antiseptic, antioxidant, antiinflammatory, and an adhesive and to seal cracks; to protect wooden and other surfaces. The bees use propolis to repair combs, to strengthen the thin borders of the comb, and to make the entrance of the hive weathertight or easier to defend. Propolis is also used as an “embalming” substance to cover the carcass of a hive invader which the bees have killed but cannot transport out of the hive. The bees cover the invader with propolis and wax, and the remains are left at the bottom or on one of the walls of the hive [2, 19]. Figure 1 illustrates the Apis mellifera collecting resinous material from leaf buds of Baccharis dracunculifolia (a) and the deposition of green propolis in the hive (b).

fig1
Figure 1: Apis mellifera collecting propolis of Baccharis dracunculifolia to production propolis in Brazil. (a) Apis mellifera collecting leaf apices Baccharis dracunculifolia; (b) deposition of green propolis cracks in the hive.

In early records are mentioned substances that cast doubt on the use or not of propolis. In Genesis (c. 1700 BC), tzori was taken to Egypt, once with honey and its healing properties are noted three times in Jeremiah. Twice, tzori came from Gilead, but it was not balm of Gilead which is produced from a tree, Commiphora opobalsamum. Assis believed that “black wax” referred to in the Egyptian Ebers papyrus (c. 1550 BC) may have been propolis. He also considered that Hebrew tzori was an early word for propolis. This occured six times in the Hebrew scriptures and was usually translated as balm or balsam [19].

Egyptians knew very well the antiputrefactive properties of propolis and used it to embalm cadavers. Greek and Roman physicians Aristoteles, Dioscorides, Pliny, and Galen were familiar with the medicinal properties of propolis. It is not known what methods were used for harvesting it in the ancient world, although writers in Greece and Rome were familiar with it. The Greek Historia Animalium referred to a substance mitys, which was probably propolis, as “a cure for bruises and suppurating sores.” According to Varro in Rome, propolis was used by physicians in making poultices, and for this reason it brings even a higher price than honey on the Via Sacra [19].

The propolis was employed as an antiseptic and cicatrizant in wound treatment and as a mouth disinfectant, with these uses being perpetuated in the Middle Ages and among Arab physicians. Propolis was also recognized by other peoples unrelated to the Old World civilizations: Incas employed propolis as an antipyretic agent, and the London pharmacopoeias of the seventeenth century listed propolis as an official drug. Between the seventeenth and twentieth centuries, the propolis became very popular in Europe on account of its antibacterial activity [18].

2.1. Publications and Patents

The first work indexed by Chemical Abstracts on propolis was in 1903, and the first patent was described in 1904 (USA—Composition for treating pins and piano strings). One hundred and nine years after the first publication in the Chemical Abstract, the number of publications on propolis reached 3,880 in journal and 2,884 in patents.

Figure 2 shows the number of publications on propolis over the decades; data were obtained by searching the Chemical Abstracts. The global interest in propolis research presents two justifications according to Pereira et al. [20], the first to present diverse biological properties and the second by high added value, the sale price of a bottle in Brazil is about 5 to 10 real.

697390.fig.002
Figure 2: Scientific productivity on propolis between the decades (Chemical Abstracts).

The scientific production about propolis by document type is the majority about journal and patents as shown in Figure 3.

697390.fig.003
Figure 3: Scientific production on propolis by document type (Chemical Abstracts).

The processed patent documents contain highly valuable legal, economic, and technical information; hence, the results obtained from their processing make it possible to obtain highly valuable information to reach conclusions useful as key elements for the design of R&D, technological surveillance, market studies, and marketing strategies [21].

Since the first patent was filed and until today, it is possible to see that there was a considerable increase in the number of patents in the last thirty years (Figure 4).

697390.fig.004
Figure 4: Scientific production on propolis by patents (Chemical Abstracts).

According to profile of patents, shown in Figure 5, China, Japan, and Russia are those that hold most of the patents. This fact can be justified by China and Russia being the largest producers of propolis. Today 42% of patents are Chinese (Figure 5), and the first Chinese patent appeared in 1993 (on “Process for production mouth freshener”). The Japanese have 15% of patents, and the first appeared in 1988 (about “Deodorants controlling mouth odor”). The first patent was obtained in 1968 on Russian “Toothpaste” and represented 12% of patents. Brazil deposited its first patent in 1997 on “Dental gel.” Some patents are presented in Table 1.

tab1
Table 1: Relationship of some of the 2,884 international patents (Chemical Abstracts).
697390.fig.005
Figure 5: Scientific production on propolis by patents and languages (Chemical Abstracts).

Suárez et al. [21] noted the trend of patent applications according to application area for the period 1972–2000 and observed a high incidence of products with medicinal and nutraceutical properties and with dermatological applications.

The scientific production on propolis and healthy patents between the decades in shown in Figure 6.

697390.fig.006
Figure 6: Scientific production on propolis and healthy by patents between the decades (Chemical Abstracts).

The inventions processed according to their priority country are which shown in Figure 7 in which the highest number of filings corresponds to China (476), followed by Japan (177), Korea and Russian with 77, and 29 and filings, respectively. Japan imports almost all the propolis used in the country: 80% comes from Brazil and 10% from China and other countries, and this is shown in their inventions, since in the analysis carried out to the content of the Japanese inventions we can see that the Brazilian propolis is the target of invention [21].

697390.fig.007
Figure 7: Scientific production on propolis and healthy by patents and languages (Chemical Abstracts).

Six percent of patents filed by 2012, refers to the use of propolis for dental treatment (Figure 8). According to Pereira et al. [20], this is one of the most widely studied applications of propolis worldwide.

697390.fig.008
Figure 8: Scientific production on propolis for dental treatment by patents and languages (Chemical Abstracts).

According to the Ministry of Development Industry and Foreign Trade of Brazil [22], the Brazilian export market of propolis in the year of 2012 was 41,721 Kg corresponding about $5,401,643. These values can be observed in Table 2.

tab2
Table 2: Brazilian propolis export market [49].

Analyzing the data, it is possible to observe that there was a drop in sales in 2011 compared to 2010. Regarding the value of the product, there was an increase of over 50% in 2012 compared to 2010. According to Aga et al. [23], the country that buys Brazilian propolis is Japan, and its extensive use in foods and beverages intended to maintain or improve human health.

3. Chemical Composition and Propolis Activity

3.1. Chemical Composition

Propolis is a complex resinous mixture which contains approximately 50% of resin and balsam, 30% of wax, 10% of essential and aromatic oils, 5% of pollen, and 5% of impurities [24]. The chemical composition of propolis is highly variable mainly due to the variability of plant species growing around the hive, from which the bees collect the exudates [18, 2528]. Additionally, propolis composition can vary depending on the seasonality, illumination, altitude, collector type, and food availability and activity developed during propolis exploitation [2933].

Much work has been conducted on the chemical composition and biological activities. Until now, more than 300 chemical constituents have been identified in propolis from different regions [34]. The main chemical classes present in propolis are flavonoids, phenolics, and aromatic compounds (Figure 9) [35, 36]. Propolis also contains some volatile oils, terpenes, and bee wax, but these compounds are not believed to contribute as significantly to the chemical properties and effects of propolis [36].

697390.fig.009
Figure 9: Some typical flavonoids and phenolics present in green propolis.

Many analytical methods have been used for separation and identification of propolis constituents. Differents compounds have been identified in ethanol extracts of propolis (Table 3).

tab3
Table 3: Identified compounds in ethanol extracts of propolis.
3.2. Method of Extraction

The method of extraction and solvent can change the chemical composition of propolis extract. Commercial products such as tablets, capsules, ampoules, and syrups are prepared with ethanolic extract of propolis. Methanol is only used for research purposes. Some varieties of propolis have solubility in water, thereby extracting water should also be considered for study [35].

3.3. Origin Botanical

The materials available to bees for production of propolis are substances actively secreted by plants as well as substances exuded from wounds in plants: lipophilic materials on leaves and leaf buds, resins, mucilages, gums, lattices, and so forth [37].

The composition of the plant source determines the chemical composition of bee glue, and it is dependent on its geographical location; as a result, its biological activity is closely related to the vegetation native to the site of collection [14, 38, 39].

Bankova [38] discusses the diversity of the chemical composition of propolis and the problem of standardization. The issue is based on the chemical composition of propolis which varies with the plant source collection. Dealing with reliable criteria for chemical standardization of different propolis types is needed, but such generally accepted criteria do not yet exist. There is still a lot of work to be done to achieve standardization of other propolis types. Working with standardization material will allow scientists to connect a particular chemical propolis type to a specific type of biological activity and formulate recommendations. Table 4 illustrates propolis of different geographic regions and their principal plant sources of chemical compounds.

tab4
Table 4: Propolis of different geographic regions and their principal plants’ sources of chemical compounds (from Bankova, 2005).
3.4. Classification of Brazilian Propolis

It was found that propolis from several regions of Brazil show different chemical composition, depending on the local flora at the site of collection [40]. The propolis from Brazil was classified in types according to its geographical origin, chemical composition, and source plant as shown in Table 5 [17, 41, 42]. More studies should be done in order to standardize propolis.

tab5
Table 5: Classification of Brazilian propolis, according to their physicochemical characteristics and location [17, 41].
3.5. Activity of Propolis

It is important to note that most of the latest investigations on new propolis constituents are connected to their biological activity. This information is summarized in Table 6. Some compounds from propolis have antibacterial activity, antitumor activity, and antiinflammatory activity, antioxidative and hepatoprotective action.

tab6
Table 6: Chemical constituents of propolis that possess known pharmacological activities.

According to Bankova et al. [34], relating the chemical constituents of propolis with biological activity enables the standardization of the application of propolis. Kumazawa et. al. [28] report that differences in the chemical composition of propolis from different sources change the spectrum of biological activity of propolis.

Some studies have been conducted correlating chemical composition and biological activity, but no tested compounds were isolated [4347].

4. Application in Medicine and Dentistry

Propolis has been found to have a wide spectrum of biological and pharmaceutical properties and has been demonstrated to have direct antimicrobial effects in vitro [48]. Some recent studies suggested that propolis can be used in medicine and dentistry. Tables 7 and 8 illustrate some studies that show the application of propolis in medicine and dentistry.

tab7
Table 7: Recent studies on application of propolis in medicine.
tab8
Table 8: Recent studies on application of propolis in dentistry.

5. Conclusions

Propolis has been used extensively as a folk medicine because of its special chemical components, strong pharmacological, properties and low toxicity. This wide spectrum of therapeutic effects makes propolis a potential candidate in several clinical scenarios. Clinical studies are now also in progress to verify the effects of propolis in the prevention and treatment of diseases.

The application of propolis is mostly in the drug or food manufacture in the form of mixtures. Current opinion is that the use of standardized preparations of propolis is safe and less toxic than many synthetic medicines, but the components of propolis are variable, and it is difficult to standardize and apply propolis. Robust manufacturing processes, standardized quality controls, and good design clinical trials are all critical steps in verifying these claims.

References

  1. W. Greenaway, T. Scaysbrook, and F. R. Whately, “The composition and plant origin of propolis: a report of work Oxford,” Bee World, vol. 71, no. 3, pp. 107–118, 1990.
  2. E. L. Ghisalberti, “Propolis: a review,” Bee World, vol. 60, no. 2, pp. 59–84, 1979.
  3. T. Matsuno, Y. Matsumoto, M. Saito, and J. Morikawa, “Isolation and characterization of cytotoxic diterpenoid isomers from propolis,” Zeitschrift für Naturforschung C, vol. 52, no. 9-10, pp. 702–704, 1997. View at Scopus
  4. N. Vynograd, I. Vynograd, and Z. Sosnowski, “A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV),” Phytomedicine, vol. 7, no. 1, pp. 1–6, 2000. View at Scopus
  5. T. Kimoto, M. Aga, K. Hino et al., “Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient of Brazilian propolis,” Anticancer Research, vol. 21, no. 1 A, pp. 221–228, 2001. View at Scopus
  6. T. Kimoto, S. Arai, M. Kohguchi et al., “Apoptosis and suppression of tumor growth by Artepillin C extracted from Brazilian propolis,” Cancer Detection and Prevention, vol. 22, no. 6, pp. 506–515, 1998. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Basnet, T. Matsuno, and R. Neidlein, “Potent free radical scavenging activity of propol isolated from Brazilian propolis,” Zeitschrift für Naturforschung C, vol. 52, no. 11-12, pp. 828–833, 1997. View at Scopus
  8. Y. K. Park, M. H. Koo, J. A. S. Abreu, M. Ikegaki, J. A. Cury, and P. L. Rosalen, “Antimicrobial activity of propolis on oral microorganisms,” Current Microbiology, vol. 36, no. 1, pp. 24–28, 1998. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Ito, F. R. Chang, H. K. Wang et al., “Anti-AIDS agents. 48. Anti-HIV activity of moronic acid derivatives and the new melliferone-related triterpenoid isolated from Brazilian propolis,” Journal of Natural Products, vol. 64, no. 10, pp. 1278–1281, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. G. A. Burdock, “Review of the biological properties and toxicity of bee propolis (propolis),” Food and Chemical Toxicology, vol. 36, no. 4, pp. 347–363, 1998. View at Publisher · View at Google Scholar · View at Scopus
  11. V. Bankova and N. Marekov, “Propolis-chemical composition and standardization,” Farmatsiya, vol. 32, pp. 8–18, 1984.
  12. C. Garcia-Vigueira, W. Greenaway, and F. Whatley, “Composition of propolis from two different Spanish regions,” Zeitschrift für Naturforschung C, vol. 47, pp. 634–637, 1992.
  13. B. Konig, “Plant sources of propolis,” Bee World, vol. 66, no. 4, pp. 136–139, 1985.
  14. Y. K. Park, S. M. Alencar, and C. L. Aguiar, “Botanical origin and chemical composition of Brazilian propolis,” Journal of Agricultural and Food Chemistry, vol. 50, no. 9, pp. 2502–2506, 2002.
  15. Y. K. Park, J. F. Paredes-Guzman, C. L. Aguiar, S. M. Alencar, and F. Y. Fujiwara, “Chemical constituents in Baccharis dracunculifolia as the main botanical origin of Southeastern Brazilian propolis,” Journal of Agricultural and Food Chemistry, vol. 52, no. 5, pp. 1100–1103, 2004. View at Scopus
  16. M. C. Marcucci, “Propolis: chemical composition, biological properties and therapeutic activity,” Apidologie, vol. 26, no. 2, pp. 83–99, 1995. View at Scopus
  17. A. Daugsch, C. S. Moraes, P. Fort, and Y. K. Park, “Brazilian red propolis—chemical composition and botanical origin,” Evidence-Based Complementary and Alternative Medicine, vol. 5, no. 4, pp. 435–441, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Castaldo and F. Capasso, “Propolis, an old remedy used in modern medicine,” Fitoterapia, vol. 73, supplement 1, pp. S1–S6, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. E. Crane, “The past and present importance of bee products to man,” in Bee Products—Properties, Applications, and Apitherapy, A. Mizrahi and Y. Lensky, Eds., pp. 1–13, Plenum Press, New York, NY, USA, 1997.
  20. A. S. Pereira, F. R. M. S. Seixas, and F. R. Aquino Neto, “Própolis: 100 anos de pesquisa e suas perspectivas futuras,” Química Nova, vol. 25, no. 2, pp. 321–326, 2002. View at Publisher · View at Google Scholar
  21. D. Suárez, D. Zayas, and F. Guisado, “Propolis: patents and technology trends for health applications,” Journal of Business Chemistry, vol. 2, no. 3, pp. 119–125, 2005.
  22. “Ministério do desenvolvimento da indústria e comércio,” http://aliceweb.mdic.gov.br.
  23. H. Aga, T. Shibuya, T. Sugimoto, M. Kurimoto, and S. Nakajima, “Isolation and identification of antimicrobial compounds in Brazilian propolis,” Bioscience, Biotechnology and Biochemistry, vol. 58, no. 5, pp. 945–946, 1994.
  24. W. Thomson, “Propolis,” Medical Journal of Australia, vol. 153, article 654, 1990.
  25. K. R. Markham, K. A. Mitchell, A. L. Wilkins, J. A. Daldy, and Y. Lu, “HPLC and GC-MS identification of the major organic constituents in New Zealand propolis,” Phytochemistry, vol. 42, no. 1, pp. 205–211, 1996. View at Scopus
  26. V. Bankova, G. Boudourova-Krasteva, J. M. Sforcin et al., “Phytochemical evidence for the plant origin of Brazilian propolis from Sao Paulo state,” Zeitschrift für Naturforschung C, vol. 54, no. 5-6, pp. 401–405, 1999. View at Scopus
  27. A. Kujumgiev, I. Tsvetkova, Y. Serkedjieva, V. Bankova, R. Christov, and S. Popov, “Antibacterial, antifungal and antiviral activity of propolis of different geographic origin,” Journal of Ethnopharmacology, vol. 64, no. 3, pp. 235–240, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Kumazawa, T. Hamasaka, and T. Nakayama, “Antioxidant activity of propolis of various geographic origins,” Food Chemistry, vol. 84, no. 3, pp. 329–339, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. H. Katircioǧlu and N. Mercan, “Antimicrobial activity and chemical compositions of Turkish propolis from different regions,” African Journal of Biotechnology, vol. 5, no. 11, pp. 1151–1153, 2006. View at Scopus
  30. V. Bankova, G. Boudourova-Krasteva, S. Popov, J. M. Sforcin, and S. R. C. Funari, “Seasonal vatiations of the chemical composition of Brazilian propolis,” Apidologie, vol. 29, no. 4, pp. 361–367, 1998. View at Scopus
  31. J. M. Sforcin, E. L. Novelli, and S. R. C. Funari, “Seasonal effect of Brazilian propolis on seric biochemical variables,” Journal of Venomous Animals and Toxins Including Tropical Diseases, vol. 8, pp. 244–254, 2000.
  32. S. Silici and S. Kutluca, “Chemical composition and antibacterial activity of propolis collected by three different races of honeybees in the same region,” Journal of Ethnopharmacology, vol. 99, no. 1, pp. 69–73, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. M. L. Castro, J. A. Cury, P. L. Rosalen et al., “Própolis do sudeste e nordeste do Brasil: influência da sazonalidade na atividade antibacteriana e composição fenólica,” Química Nova, vol. 30, pp. 1512–1521, 2007.
  34. V. S. Bankova, S. L. de Castro, and M. C. Marcucci, “Propolis: recent advances in chemistry and plant origin,” Apidologie, vol. 31, no. 1, pp. 3–15, 2000. View at Scopus
  35. Y. Xu, L. Luo, B. Chen, and Y. Fu, “Recent development of chemical components in propolis,” Frontiers of Biology in China, vol. 4, no. 4, pp. 385–391, 2009. View at Publisher · View at Google Scholar
  36. J. O. Schmidt, “Chemical composition and application,” in Bee Products—Properties, Applications, and Apitherapy, A. Mizrahi and Y. Lensky, Eds., pp. 15–26, New York, New York, NY, USA, 1997.
  37. E. Crane, Beekeping: Science, Practice and World Resources, Butterworth Heinemann, London, UK, 1988.
  38. V. Bankova, “Chemical diversity of propolis and the problem of standardization,” Journal of Ethnopharmacology, vol. 100, no. 1-2, pp. 114–117, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. R. Christov, B. Trusheva, M. Popova, V. Bankova, and M. Bertrand, “Chemical composition of propolis from Canada, its antiradical activity and plant origin,” Natural Product Research, vol. 19, no. 7, pp. 673–678, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. B. Trusheva, M. Popova, V. Bankova et al., “Bioactive constituents of Brazilian red propolis,” Evidence-Based Complementary and Alternative Medicine, vol. 3, no. 2, pp. 249–254, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. K. Park, M. Ikegaki, S. M. Alencar, and F. F. Moura, “Evaluation of Brazilian propolis by both physicochemical methods and biological activity,” Honeybee Science, vol. 21, no. 2, pp. 85–90, 2000.
  42. S. M. Alencar, T. L. C. Oldoni, M. L. Castro et al., “Chemical composition and biological activity of a new type of Brazilian propolis: red propolis,” Journal of Ethnopharmacology, vol. 113, no. 2, pp. 278–283, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. J. F. M. da Silva, M. C. de Souza, S. R. Matta, M. R. de Andrade, and F. V. N. Vidal, “Correlation analysis between phenolic levels of Brazilian propolis extracts and their antimicrobial and antioxidant activities,” Food Chemistry, vol. 99, no. 3, pp. 431–435, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Salomão, P. R. S. Pereira, L. C. Campos et al., “Brazilian propolis: correlation between chemical composition and antimicrobial activity,” Evidence-Based Complementary and Alternative Medicine, vol. 5, no. 3, pp. 317–324, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. I. S. R. Cabral, T. L. C. Oldoni, A. Prado, R. M. N. Bezerra, and S. M. Alencar, “Composição fenólica, atividade antibacteriana e antioxidante da própolis vermelha brasileira,” Química Nova, vol. 32, no. 6, pp. 1523–1527, 2009.
  46. E. Gregoris and R. Stevanato, “Correlations between polyphenolic composition and antioxidant activity of Venetian propolis,” Food and Chemical Toxicology, vol. 48, no. 1, pp. 76–82, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. A. A. Righi, T. R. Alves, G. Negri, L. M. Marques, H. Breyer, and A. Salatino, “Brazilian red propolis: unreported substances, antioxidant and antimicrobial activities,” Journal of the Science of Food and Agriculture, vol. 91, pp. 2363–2370, 2011.
  48. A. Ugur and T. Arslan, “An in vitro study on antimicrobial activity of propolis from Mugla Province of Turkey,” Journal of Medicinal Food, vol. 7, no. 1, pp. 90–94, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. L. C. Paviani, C. Dariva, M. C. Marcucci, and F. A. Cabral, “Supercritical carbon dioxide selectivity to fractionate phenolic compounds from the dry ethanolic extract of propolis,” Journal of Food Process Engineering, vol. 33, no. 1, pp. 15–27, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. V. S. Bankova, S. S. Popov, and N. L. Marekov, “A study on flavonoids of propolis,” Journal of Natural Products, vol. 46, no. 4, pp. 471–474, 1983. View at Scopus
  51. V. Bankova, A. Dyulgerov, S. Popov, and N. Marekov, “A GC/MS study of the propolis phenolic constituents,” Zeitschrift für Naturforschung C, vol. 42, pp. 147–151, 1987.
  52. G. Boudourova-Krasteva, V. Bankova, J. M. Sforcin, N. Nikolova, and S. Popov, “Phenolics from Brazilian propolis,” Zeitschrift für Naturforschung C, vol. 52, no. 9-10, pp. 676–679, 1997. View at Scopus
  53. M. C. Marcucci, J. Rodriguez, F. Ferreres, and V. Bankova, “Chemical composition of Brazilian propolis from Sao Paulo state,” Zeitschrift für Naturforschung C, vol. 53, no. 1-2, pp. 117–119, 1998. View at Scopus
  54. S. Tazawa, T. Warashina, and T. Noro, “Studies on the constituents of Brazilian propolis. II,” Chemical and Pharmaceutical Bulletin, vol. 47, no. 10, pp. 1388–1392, 1999. View at Scopus
  55. S. Kumazawa, R. Ueda, T. Hamasaka, S. Fukumoto, T. Fujimoto, and T. Nakayama, “Antioxidant prenylated flavonoids from propolis collected in Okinawa, Japan,” Journal of Agricultural and Food Chemistry, vol. 55, no. 19, pp. 7722–7725, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. M. L. Castro, A. M. D. Nascimento, M. Ikegaki, C. M. Costa-Neto, S. M. Alencar, and P. L. Rosalen, “Identification of a bioactive compound isolated from Brazilian propolis type 6,” Bioorganic and Medicinal Chemistry, vol. 17, no. 14, pp. 5332–5335, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Lotti, M. C. Fernandez, A. L. Piccinelli, O. Cuesta-Rubio, I. M. Hernández, and L. Rastrelli, “Chemical constituents of red Mexican propolis,” Journal of Agricultural and Food Chemistry, vol. 58, no. 4, pp. 2209–2213, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. M. P. Popova, K. Graikou, I. Chinou, and V. S. Bankova, “GC-MS profiling of diterpene compounds in Mediterranean propolis from Greece,” Journal of Agricultural and Food Chemistry, vol. 58, no. 5, pp. 3167–3176, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Petrova, M. Popova, C. Kuzmanova et al., “New biologically active compounds from Kenyan propolis,” Fitoterapia, vol. 81, no. 6, pp. 509–514, 2010. View at Publisher · View at Google Scholar
  60. B. Trusheva, M. Popova, E. B. Koendhori, I. Tsvetkova, C. Naydenski, and V. Bankova, “Indonesian propolis: chemical composition, biological activity and botanical origin,” Natural Product Research, vol. 25, no. 6, pp. 606–613, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. S. A. Shaheen, M. H. Zarga, I. K. Nazer, R. M. Darwish, and H. I. Al-Jaber, “Chemical constituents of Jordanian propolis,” Natural Product Research, vol. 25, no. 14, pp. 1312–1318, 2011. View at Publisher · View at Google Scholar
  62. C. Lotti, A. L. Piccineli, C. Arevalo, et al., “Constituents of Hondurian propolis with inhibitory effects on Saccharomyces cerevisiae multidrug resistance protein Pdr5p,” Journal of Agricultural and Food Chemistry, vol. 60, no. 42, pp. 10540–10545, 2012. View at Publisher · View at Google Scholar
  63. V. Bankova, R. Christov, S. Popov, O. Pureb, and G. Bocari, “Volatile constituents of propolis,” Zeitschrift für Naturforschung C, vol. 49, pp. 6–10, 1994.
  64. V. Bankova, R. Christov, A. Kujumgiev, M. C. Marcucci, and S. Popov, “Chemical composition and antibacterial activity of Brazilian propolis,” Zeitschrift für Naturforschung C, vol. 50, no. 3-4, pp. 167–172, 1995. View at Scopus
  65. E. Nagy, V. Papay, G. Litkei, and Z. Dinya, “Investigation of the chemical constituents, particularly the flavonoid components, of propolis and Populi gemma by GC/MS method,” Studies in Organic Chemistry, vol. 23, pp. 223–232, 1986.
  66. S. A. Popravko and M. V. Sokolov, “Plant sources of propolis,” Pchelovodstvo, vol. 2, pp. 28–29, 1980 (Russian).
  67. M. C. Marcucci and V. S. Bankova, “Chemical composition, plant origin and biological activity of Brazilian propolis,” Current Topics in Phytochemistry, vol. 2, pp. 115–123, 1999.
  68. F. A. Tomás-Barberán, C. García-Vigueira, P. Vit-Olivier, F. Ferreres, and F. Tomás-Lorente, “Phytochemical evidence for the botanical origin f tropical propolis from Venezuela,” Phytochemistry, vol. 34, no. 1, pp. 191–196, 1993. View at Publisher · View at Google Scholar
  69. O. Cuesta-Rubio, B. A. Frontana-Uribe, T. Ramírez-Apan, and J. Cárdenas, “Polyisoprenylated benzophenones in Cuban propolis; biological activity of nemorosone,” Zeitschrift für Naturforschung C, vol. 57, no. 3-4, pp. 372–378, 2002. View at Scopus
  70. B. Trusheva, M. Popova, H. Naydenski, I. Tsvetkova, J. G. Rodriguez, and V. Bankova, “New polyisoprenylated benzophenones from Venezuelan propolis,” Fitoterapia, vol. 75, no. 7-8, pp. 683–689, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. Y. K. Park, S. M. Alencar, A. R. P. Scamparini, and C. L. Aguiar, “Própolis produzida no Sul do Brasil, Argentina e Uruguai: evidências fitoquímicas de sua origem vegetal,” Ciência Rural, vol. 32, no. 6, pp. 997–1003, 2002.
  72. A. H. Banskota, Y. Tezuka, I. K. Adnyana et al., “Hepatoprotective and anti-Helicobacter pylori activities of constituents from Brazilian propolis,” Phytomedicine, vol. 8, no. 1, pp. 16–23, 2001. View at Scopus
  73. T. Matsuno, Y. Matsumoto, M. Saito, and J. Mprikawa, “Antitumor benzopyran derivative of propolis,” Chemical Abstracts, vol. 126, Article ID 39814j, 1997.
  74. T. Matsuno, M. Saito, Y. Matsumoto, and J. Morikawa, “A new benzo-γ-pyran derivative isolated from propolis,” Zeitschrift für Naturforschung C, vol. 53, no. 11-12, pp. 1037–1039, 1998. View at Scopus
  75. T. Hashimoto, H. Aga, A. Tabuchi et al., “Anti-Helicobacter pylori compounds in Brazilian propolis,” Natural Medicines, vol. 52, no. 6, pp. 518–520, 1998. View at Scopus
  76. D. Grunberger, R. Banerjee, K. Eisinger et al., “Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis,” Experientia, vol. 44, no. 3, pp. 230–232, 1988. View at Scopus
  77. O. K. Mirzoeva and P. C. Calder, “The effect of propolis and its components on eicosanoid production during the inflammatory response,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 55, no. 6, pp. 441–449, 1996. View at Publisher · View at Google Scholar · View at Scopus
  78. B. Konig and J. H. Dustmann, “Fortschritte der celler untersuchungen zur antivirotischen aktivität von propolis,” Apidologie, vol. 15, pp. 228–230, 1985.
  79. V. R. Villanueva, M. Barbier, M. Gonnet, and P. Lavie, “The flavonoids of propolis. Isolation of a new bacteriostatic substance: pinocembrin (dihydroxy-5, 7 flavanone),” Annales de l'Institut Pasteur, vol. 118, no. 1, pp. 84–87, 1970. View at Scopus
  80. J. Metzner, E. M. Schneidewind, and E. Friedrich, “On the effects of propolis and pinocembrin on blastomyces,” Pharmazie, vol. 32, no. 11, p. 730, 1977. View at Scopus
  81. P. Basnet, K. Matsushige, K. Hase, S. Kadota, and T. Namba, “Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury models,” Biological and Pharmaceutical Bulletin, vol. 19, no. 11, pp. 1479–1484, 1996. View at Scopus
  82. M. Paintz and J. Metzner, “Zur iokalanästhetischen wirkung von propolis und einigen Inhaltsstoffen,” Pharmazie, vol. 34, pp. 839–841, 1979.
  83. M. Miyakado, T. Kato, N. Ohno, and T. J. Mabry, “Pinocembrin and (+)-β-eudesmol from Hymenoclea monogyra and Baccharis glutinosa,” Phytochemistry, vol. 15, no. 5, p. 846, 1976. View at Scopus
  84. K. Hayashi, S. Komura, N. Isaji, N. Ohishi, and K. Yagi, “Isolation of antioxidative compounds from Brazilian propolis: 3,4-dihydroxy-5-prenylcinnamic acid, a novel potent antioxidant,” Chemical and Pharmaceutical Bulletin, vol. 47, no. 11, pp. 1521–1524, 1999. View at Scopus
  85. T. Kimoto, S. Koya-Miyata, K. Hino et al., “Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protection from it by Brazilian propolis and artepillin C,” Virchows Archiv, vol. 438, no. 3, pp. 259–270, 2001. View at Publisher · View at Google Scholar · View at Scopus
  86. Y. Akao, H. Maruyama, K. Matsumoto et al., “Cell growth inhibitory effect of cinnamic acid derivatives from propolis on human tumor cell lines,” Biological and Pharmaceutical Bulletin, vol. 26, no. 7, pp. 1057–1059, 2003. View at Scopus
  87. Y. K. Park, I. Fukuda, H. Ashida et al., “Suppression of dioxin mediated aryl hydrocarbon receptor transformation by ethanolic extracts of propolis,” Bioscience, Biotechnology and Biochemistry, vol. 68, no. 4, pp. 935–938, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Russo, V. Cardile, F. Sanchez, N. Troncoso, A. Vanella, and J. A. Garbarino, “Chilean propolis: antioxidant activity and antiproliferative action in human tumor cell lines,” Life Sciences, vol. 76, no. 5, pp. 545–558, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. Y. Inokuchi, M. Shimazawa, Y. Nakajima, S. Suemori, S. Mishima, and H. Hara, “Brazilian green propolis protects against retinal damage in vitro and in vivo,” Evidence-Based Complementary and Alternative Medicine, vol. 3, no. 1, pp. 71–77, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. H. Li, A. Kapur, J. X. Yang et al., “Antiproliferation of human prostate cancer cells by ethanolic extracts of Brazilian propolis and its botanical origin,” International Journal of Oncology, vol. 31, no. 3, pp. 601–606, 2007. View at Scopus
  91. T. Shimizu, A. Hino, A. Tsutsumi, K. P. Yong, W. Watanabe, and M. Kurokawa, “Anti-influenza virus activity of propolis in vitro and its efficacy against influenza infection in mice,” Antiviral Chemistry and Chemotherapy, vol. 19, no. 1, pp. 7–13, 2008. View at Scopus
  92. R. M. Darwish, R. J. A. Fares, M. H. A. Zarga, and I. K. Nazer, “Antibacterial effect of Jordanian propolis and isolated flavonoids against human pathogenic bacteria,” African Journal of Biotechnology, vol. 9, no. 36, pp. 5966–5974, 2010. View at Scopus
  93. B. Kouidhi, T. Zmantar, and A. Bakhrouf, “Anti-cariogenic and anti-biofilms activity of Tunisian propolis extract and its potential protective effect against cancer cells proliferation,” Anaerobe, vol. 16, no. 6, pp. 566–571, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. K. W. Cheung, D. M. Y. Sze, W. K. Chan, R. X. Deng, W. Tu, and G. C. F. Chan, “Brazilian green propolis and its constituent, artepellin C inhibits allogenic activated human CD4 T cells expansion and activation,” Journal of Ethnopharmacology, vol. 138, no. 2, pp. 463–471, 2011.
  95. M. J. Valente, A. F. Baltazar, R. Henrique, L. Estevinho, and M. Carvalho, “Biological activities of Portuguese propolis: protection against free radical-induced erythrocyte damage and inhibition of human renal cancer cell growth in vitro,” Food and Chemical Toxicology, vol. 49, no. 1, pp. 86–92, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. J. Shvarzbeyn and M. Huleihel, “Effect of propolis and caffeic acid phenethyl ester (CAPE) on NFκB activation by HTLV-1 Tax,” Antiviral Research, vol. 90, no. 3, pp. 108–115, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. T. Kamiya, H. Nishihara, H. Hara, and T. Adachi, “Ethanol extract of Brazilian red propolis induces apoptosis in human breast cancer MCF-3 cells through endoplasmic reticulum stress,” Journal of Agricultural and Food Chemistry, vol. 60, no. 44, pp. 11065–11070, 2012. View at Publisher · View at Google Scholar
  98. G. C. Franchi Jr., C. S. Moraes, V. C. Toreti, A. Daugsch, A. E. Nowill, and Y. K. Park, “Comparison of effects of the ethanolic extracts of Brazilian propolis on human leukemic cells as assessed with the MTT assay,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 918956, 6 pages, 2012. View at Publisher · View at Google Scholar
  99. C. P. Chuu, H. P. Lin, M. F. Ciacco, et al., “Caffeic acid phenethyl ester suppresses the proliferation on human prostate cancer cells through inhibition of p70S6K and Akt signaling networks,” Cancer Prevention Research, vol. 5, no. 5, pp. 788–797, 2012. View at Publisher · View at Google Scholar
  100. K. Yasukawa, S. Y. Yu, S. Tsutsumi, M. Kurokawa, and Y. K. Park, “Inhibitory effects of Brazilian propolis on tumor promotion in two-stage mouse skin carcinogenesis,” Journal of Pharmacy and Nutrition Sciences, vol. 2, pp. 71–76, 2012.
  101. R. Zukowska-Markiewicz, M. H. Borawska, A. Fiedorowicz, S. K. Naliwajko, D. Sawicka, and H. Car, “Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line,” Evidence-Based Complementary and Alternative Medicine, vol. 13, article 50, 2013. View at Publisher · View at Google Scholar
  102. K. Ikeno, T. Ikeno, and C. Miyazawa, “Effects of propolis on dental caries in rats,” Caries Research, vol. 25, no. 5, pp. 347–351, 1991. View at Scopus
  103. H. Koo, P. L. Rosalen, J. A. Cury, Y. K. Park, M. Ikegaki, and A. Sattler, “Effect of Apis mellifera propolis from two Brazilian regions on caries development in desalivated rats,” Caries Research, vol. 33, no. 5, pp. 393–400, 1999. View at Publisher · View at Google Scholar · View at Scopus
  104. H. Koo, A. M. Vacca Smith, W. H. Bowen, P. L. Rosalen, J. A. Cury, and Y. K. Park, “Effects of Apis mellifera propolis on the activities of streptococcal glucosyltransferases in solution and adsorbed onto saliva-coated hydroxyapatite,” Caries Research, vol. 34, no. 5, pp. 418–426, 2000. View at Scopus
  105. H. Koo, B. P. F. A. Gomes, P. L. Rosalen, G. M. B. Ambrosano, Y. K. Park, and J. A. Cury, “In vitro antimicrobial activity of propolis and Arnica montana against oral pathogens,” Archives of Oral Biology, vol. 45, no. 2, pp. 141–148, 2000. View at Publisher · View at Google Scholar · View at Scopus
  106. H. Koo, J. A. Cury, P. L. Rosalen, G. M. B. Ambrosano, M. Ikegaki, and Y. K. Park, “Effect of a mouthrinse containing selected propolis on 3-day dental plaque accumulation and polysaccharide formation,” Caries Research, vol. 36, no. 6, pp. 445–448, 2002. View at Scopus
  107. H. Koo, P. L. Rosalen, J. A. Cury et al., “Effect of a new variety of Apis mellifera propolis on mutans streptococci,” Current Microbiology, vol. 41, no. 3, pp. 192–196, 2000. View at Publisher · View at Google Scholar · View at Scopus
  108. H. Koo, S. K. Pearson, K. Scott-Anne et al., “Effects of apigenin and tt-farnesol on glucosyltransferase activity, biofilm viability and caries development in rats,” Oral Microbiology and Immunology, vol. 17, no. 6, pp. 337–343, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. H. Koo, B. Schobel, K. Scott-Anne et al., “Apigenin and tt-farnesol with fluoride effects on S. mutans biofilms and dental caries,” Journal of Dental Research, vol. 84, no. 11, pp. 1016–1020, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. M. F. Hayacibara, H. Koo, P. L. Rosalen et al., “In vitro and in vivo effects of isolated fractions of Brazilian propolis on caries development,” Journal of Ethnopharmacology, vol. 101, no. 1–3, pp. 110–115, 2005. View at Publisher · View at Google Scholar · View at Scopus
  111. S. Duarte, P. L. Rosalen, M. F. Hayacibara et al., “The influence of a novel propolis on mutans streptococci biofilms and caries development in rats,” Archives of Oral Biology, vol. 51, no. 1, pp. 15–22, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. S. A. D. C. Duailibe, A. G. Gonçalves, and F. J. M. Ahid, “Effect of a propolis extract on Streptococcus mutans counts in vivo,” Journal of Applied Oral Science, vol. 15, no. 5, pp. 420–423, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. M. J. Kini, C. S. Kini, B. H. Kim et al., “Antimicrobial effect of Korean propolis against the mutans streptococci isolated from Korean,” Journal of Microbiology, vol. 49, no. 1, pp. 161–164, 2011. View at Publisher · View at Google Scholar