Propolis is a honey bee product known for centuries for its biological and pharmacological properties. It has been extensively used due to its antibacterial, antiseptic, anti-inflammatory, and anesthetic activities. Propolis has become the subject of numerous studies developed and carried out all over the world in order to analyze its chemical composition as well as medicinal properties.
Propolis is a resinous yellow-brown to dark brown, sometimes green substance collected by worker honey bees from the growing parts of trees and shrubs (e.g., leaf buds, trunk wounds). The bees pack the propolis on their hind legs, and carry it back to their colony, where it is combined with beeswax and used by worker "hive" bees as a sealant and sterilant in the colony nest. These workers take the resinous material and add salivary secretions and wax flakes to it, then use the new product for numerous protective purposes as bee propolis. The bees use it to coat the inside of the hive, including the passageway and the brood chambers. Propolis changes consistency with temperature. At temperatures below 150C it is hard and brittle but becomes more pliable and stickier at higher temperatures (25-450C).
Propolis protects the hive in two ways: (1) it structurally reinforces the hive itself; (2) it protects the hive from microbial infection or predator infestation. Propolis has been shown to kill Bacillus larvae, the most important bacterial disease of bees.1
History of Propolis Usage
The history of bees and their products can be traced back to c. 13,000 BC. A certain amount of knowledge is attested by depictions of the bee and of hive beekeeping found during excavations. Rock paintings also provide some of the earliest evidence of gathering honey from wild colonies. At some point humans began to domesticate wild bees in hives made from hollow logs, wooden containers, pottery vessels, and woven straw baskets. Honey bees have used propolis for millions of years, and humans have used it for thousands.2 Both species find it immensely useful and beneficial. Much of the bees' success in surviving through the ages may be credited to propolis. We may yet discover we have only just scratched the surface of the benefits of this resinous wonder.
The Greek physician, Hippocrates, prescribed the use of propolis to help heal internal and external sores and ulcers. Pliny, the Roman scholar, wrote much on the use of resins such as propolis in his massive book, Natural History. He touts the abilities of propolis to reduce swelling, soothe pain, and heal sores, to name a few.3
In The History of Plants, written by John Gerard in 1597, propolis was noted for its ability to provide swift and effective healing for many conditions. During this era, propolis was used in many different healing ointments. Propolis has been used since early times, for various purposes, and especially as a medicine, particularly because of its antimicrobial properties.4
The ancient Greeks, Romans, and Egyptians were aware of the healing properties of propolis and made extensive use of it as a medicine. Ancient Greek texts refer to the substance as a "cure for bruises and suppurating sores", and in Rome physicians used propolis in the making of poultices. The Hebrew word for propolis is “tzori”, and the therapeutic properties of tzori are mentioned throughout the Old Testament. The biblical Balm of Gilead (tzori Gilead in Hebrew) is nearly indistinguishable from propolis.
Ancient Egyptians depicted propolis-making bees on vases and other ornaments and used it to alleviate many ailments. The Egyptians had learnt from the bees, which use propolis as an “embalming” substance: the bees cover the carcass of a killed invader, which cannot be transported out of the hive, with propolis and wax. In this way, the bees restrain spread of infection caused by the decomposing carcass.
In the years 1967–1973, a series of studies were performed in Denmark, which proved the effectiveness of propolis in treatment - as well as the fact that it produces almost no side effects. Dr. Karl Lund Aagaard, a Danish biologist, was dubbed “Dr. Propolis” for his 20+ years of propolis collecting and research. After observing the effects of propolis on more than 50,000 patients in Scandinavia, Dr Aagaard drew the following conclusions:
The field of influence of Propolis is extremely broad. It includes cancer, infection of the urinary tract, swelling of the throat, gout, open wounds, sinus congestion, colds, influenza, bronchitis, gastritis, diseases of the ears, periodontal disease, intestinal infections, ulcers, eczema eruptions, pneumonia, arthritis, lung disease, stomach virus, headaches, Parkinson’s disease, bile infections, sclerosis, circulation deficiencies, warts, conjunctivitis and hoarseness.5
Records from 12th-century Europe describe medical preparations using propolis for the treatment of mouth and throat infections, as well as dental caries.
Collection and Commercial Usage
Propolis is collected by commercial beekeepers, either by scraping the substance from wooden hive parts, or by using specially constructed collection mats. The raw product undergoes secondary processing to remove beeswax and other impurities before being used in a variety of natural health care products (e.g., lozenges, tinctures, ointments, drinks). One of the non-medicinal uses of propolis is as a varnish, and it has been suggested that the special properties of Stradivarius violins may be partly due to the type of propolis used, although the claim cannot be substantiated.
Chemical Properties and Composition of Propolis
The composition of propolis can vary according to the geographic locations from where the bees obtained the ingredients. Propolis is made up of phenolic compounds, beeswax, lipids and wax, flavonoids, terpenes (e.g. B-eudesmol), bio-elements (e.g. manganese, zinc, and copper), and other substances. One of these “other substances” 3-›4-hydroxy-3,5-bis(3-methyl-2-butenyl)phenyl-2-propenoic acid, or "Artepillin C", has been found to show antiseptic activity, antioxidant activity, and strong anti-tumor activity.6, 7, 8, 9, 10, 11, 12
At least 180 different compounds have been identified so far in propolis. This table provides the major chemicals found in propolis:
The most important pharmacologically-active constituents in propolis are the flavones, flavonols, and flavanones (collectively called flavonoids), and various phenolics and aromatics. Flavonoids play a major role in plant pigmentation. However, the flavonoids present in propolis are different in composition to those normally found in plants, since propolis flavonoids are not glycosides (i.e., they do not have sugar molecules attached to their chemical structure). Many flavonoids found in plants are glycosides.
Flavonoids are thought to account for much of the biological activity in propolis13, although other phenolic compounds are also involved. At least 38 flavonoids have been found in propolis, including galangin, kaempferol, quercetin, pinocembrin, pinostrobin and pinobanksin.14 Some of the other phenolics include cinnamic alcohol, cinnamic acid, vanillin, benzyl alcohol, benzoic acid, and caffeic and ferulic acid.
The chemical composition of propolis is highly variable because of the broad range of plants visited by honey bees when collecting the substance. Honey bees have been reported to collect propolis from numerous tree species such as poplars, alders and birches, chestnut, ash, various prunus and willows. Variations in the beeswax content of raw propolis also affect the chemical composition.
Studies indicate that the plant resins collected by bees are at least partially altered by bees prior to use in the hive. Propolis has some nutritive value, apart from the presence of small amounts of proteins, amino acids, minerals and sugars. Vitamins include small amounts of vitamins A, B1, B2, B6, C and E.15
Medicinal Properties and Usage of Propolis
Propolis is truly a fascinating compound that has a wide range of therapeutic applications. Propolis exhibits many biological properties, including immunomodulatory, anti‐inflammatory, antioxidant, antibacterial, antiviral, antifungal and antiparasitic activities, among others. Studies have been carried out using propolis from different geographic regions. Although interesting, this makes the standardization of biological assays difficult, since different propolis samples may have different chemical compositions and so do not allow comparison between results. As reported elsewhere,16 a universal standardization would be impossible and propolis' biological action should be linked to its chemical composition and plant sources.
The following are specific therapeutic effects:
Antimicrobial Effects
Because of its strong antimicrobial activity, propolis is often known as a “natural antibiotic”. Many studies have shown an inhibitory effect on a variety of micro-organisms – antibacterial, antiviral and antifungal. Active components of propolis showing an antibacterial effect include pinocembrin, galangin, caffeic acid and ferulic acid. Propolis has been found to inhibit the synthesis of protein by bacteria, which may account for at least some of its antimicrobial effects. Antiviral components include caffeic acid, lutseolin and quercetin. Antifungal components include pinocembrin, pinobanksin, caffeic acid, benzyl ester, sakuranetin and pterostilbene. Keep in mind that the bees mix saliva or “bee lymph derived secretions” with plant resins in making propolis.17
Anticancer - Antitumor Effects
Propolis has been shown to possess anticancer properties. Two main immune-potent chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. Propolis, CAPE, and artepillin C have been shown to exert summative immunosuppressive function on T lymphocyte subsets but paradoxically activate macrophage function.18 On the other hand, they also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cell proliferation via its anti-inflammatory effects; decreasing the cancer stem cell populations; blocking specific oncogene signaling pathways; exerting antiangiogenic effects; and modulating the tumor microenvironment. These findings indicate that artepillin C activates the immune system and possesses direct antitumor activity.
The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens.19, 20, 21
Wound Healing and Tissue Repair Effects
Propolis has been shown to stimulate various enzyme systems, cell metabolism, circulation and collagen formation, as well as improve the healing of burn wounds.22, 23 These effects have been shown to be, in part, the result of the presence of arginine in propolis.24 Propolis was found to be superior to standard wound treatment products in trials on rats.25 Propolis tissue regeneration properties, including healing, are possibly due to its antioxidant activity.26 Whenever free radicals are produced, they hamper or even block cell regeneration. Removal of free radicals by propolis flavonoids would allow regeneration of an ill organ or tissue in an ordinary way.
Gastro-Intestinal Effects
Propolis has been shown to inhibit the development of externally-induced stomach ulcers in rats.27 Several studies have shown propolis to be effective in treating the giardia parasite.28, 29, 30 Propolis has also been shown to improve ulcerative colitis in animal models.31, 32, 33, 34, 35
Skin Infection Effects
The flavonoids and caffeic acid derivatives of propolis have been shown to be effective in inhibiting the growth of yeasts and fungi responsible for such skin infections as ringworm and athlete's foot.36
Anti-Inflammatory Effects
Studies on mice have shown that extracts of propolis have an anti-inflammatory effect due to the flavonoids, artepillin C and caffeic acid compounds.37, 38, 39 These results suggest that propolis potentially has a strong anti-inflammatory activity.
Analgesic Effects
Propolis and some of its components produce analgesia, which in some studies has been shown to be 3 times as powerful as cocaine and 52 times that of procaine, when tested in rabbit cornea.40 The analgesic effect has been shown in part to be produced by pinocembrin, pinostrobin, caffeic acid esters components in propolis.41, 42, 43
The analgesic effect may explain why propolis has been used for centuries in the treatment of sore throats and mouth sores. An analgesic ointment for dentistry using propolis was patented in Europe in 1983.44
Effects on Immune System
Propolis has been shown to stimulate an immune response in aged mice.45 In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity.46, 47, 48 Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production have also been demonstrated.49
Propolis has been shown to stimulate antibody formation in immunized mice. In a joint US-Polish study, spleen cells producing antibodies in mice administered a propolis extract were three times greater than controls. A second dose administered 24 hours later produced an even larger effect, although further doses reduced the effect.50
Propolis has been shown to suppress HIV-1 replication and modulate in vitro immune responses, and, according to the authors, “May constitute a non-toxic natural product with both anti-HIV-1, and immunoregulatory effects.”51
Cardiovascular Effects
In animal studies it has been shown that propolis can reduce blood pressure, produce a sedative effect, and maintain serum glucose.52, 53, 54, 55, 56
Liver Protective
Propolis exhibits protective effects against hepatocyte injury owing to its cytoprotective, antioxidant and anti-inflammatory effects. Propolis has also been shown to protect the liver against numerous toxic chemicals including alcohol (ethanol) and tetrachloride in rats.57, 58, 59, 60 Furthermore, it was found to protect against oxidative-liver injury in animals exposed to cold stress or cigarette smoke.61, 62
Adverse Effects
Propolis has been shown not to be toxic to humans or mammals unless very large quantities are administered.63, 64 Contact dermatitis is a well-documented allergic reaction to propolis.65, 66 Initial reports were made by beekeepers, who came into daily contact with the raw product.67, 68 Allergic reactions are now also reported in the general population, due to the more widespread use of products containing propolis. Dermatitis is relieved once the skin is no longer in contact with the propolis product. It is therefore recommended that with all preparations intended for human use, usage is ceased whenever there is an allergic reaction.
Very few other adverse reactions to propolis have been documented in the literature, and the product is considered generally not to be harmful. Rare cases of oral inflammation and ulceration, mouth edema (swelling) and stomatitis have been reported, however, as a result of oral ingestion of propolis.69, 70
Commercial Usage of Propolis
Raw propolis is collected by beekeepers and sold in bulk to companies that refine the product and turn it into usable extracts. Main commercial uses of propolis are as a dietary supplement and therapeutic. Propolis is sold in tablets (singularly, or in combination with other substances such as pollen, royal jelly and non-hive products). In Japan, the use of propolis is permitted as a preservative in frozen fish.
Tinctures and lozenges are popular treatment for sore throats, and tinctures are often used to treat cuts, mouth sores and skin rashes. For internal use, 1-3 ml dose three times daily of a 1:10 tincture are typical, but higher doses can use used if necessary. Propolis tincture is normally diluted in water, producing a cloudy liquid. For external use, the 1:10 tincture is diluted in water, and used as a lotion or gargle.
Propolis is a stable product but should nevertheless be stored in airtight containers in the dark, preferably away from excessive and direct heat. Propolis does not lose much of its antibiotic activity, even when stored for 12 months or longer. Because of its antioxidant and antimicrobial activities, microbial contamination is not considered to be a problem with propolis, either in the raw form, or as extracts.
Despite the considerable promise that propolis will be an efficacious and safe compound for cancer therapy and chemoprevention, it has by no means been embraced by the cancer community as a panacea for all ills. The single most important reason for this reticence has been the reduced systemic bioavailability of orally administered propolis. The development of a delivery system that enables parenteral administration of propolis in an aqueous phase medium will allow us to harness the potential of this promising anti-cancer agent in the clinical arena.
World propolis production is increasing substantially. Major producers include China, Brazil, U.S., Australia, Uruguay and Japan. Unfortunately, concentrations of lead above maximum allowable levels for food products have been found in propolis. Studies have shown that lead levels may be reduced by placement of hives away from areas with heavy air pollution. Propolis destined for commercial use should be routinely tested for lead concentration. Brazilian propolis is of the highest quality available, whereas Chinese propolis has been noted for excessive lead.
“Bee” warned however, that some individuals are sensitive to propolis and caution should be taken when beginning to consume it.
References
Mlagan, V., and D. Sulimanovic. Action of propolis solutions on Bacillus larvae. Apiacta; an international technical magazine of apicultural and economic information (1982).
Simone-Finstrom, Michael, and Marla Spivak. Propolis and bee health: the natural history and significance of resin use by honey bees. Apidologie 41, no. 3 (2010): 295-311.
Kuropatnicki, Andrzej K., Ewelina Szliszka, and Wojciech Krol. Historical aspects of propolis research in modern times. Evidence-Based Complementary and Alternative Medicine2013 (2013).
Crane, Eva. The past and present importance of bee products to man. In Bee Products, pp. 1-13. Springer, Boston, MA, 1997.
Elkins, Rita. Bee Pollen/Royal Jelly/Propolis/Honey. Houghton Mifflin Harcourt, 1996.
Kimoto, Tetsuo, Shigeyuki Arai, Michihiro Kohguchi, Miho Aga, Yutaka Nomura, Mark J. Micallef, Masashi Kurimoto, and Keiichiro Mito. Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis. Cancer detection and prevention 22, no. 6 (1998): 506-515.
Matsuno, T., S. K. Jung, Y. Matsumoto, M. Saito, and J. Morikawa. Preferential cytotoxicity to tumor cells of 3, 5-diprenyl-4-hydroxycinnamic acid (artepillin C) isolated from propolis. Anticancer Research 17, no. 5A (1997): 3565-3568.
Ahn, Mok-Ryeon, Kazuhiro Kunimasa, Toshiro Ohta, Shigenori Kumazawa, Miya Kamihira, Kazuhiko Kaji, Yoshihiro Uto, Hitoshi Hori, Hideko Nagasawa, and Tsutomu Nakayama. Suppression of tumor-induced angiogenesis by Brazilian propolis: major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation. Cancer letters252, no. 2 (2007): 235-243.
Messerli, Shanta M., Mok‐Ryeon Ahn, Kazuhiro Kunimasa, Miyako Yanagihara, Tomoki Tatefuji, Ken Hashimoto, Victor Mautner et al. Artepillin C (ARC) in Brazilian green propolis selectively blocks oncogenic PAK1 signaling and suppresses the growth of NF tumors in mice. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 23, no. 3 (2009): 423-427.
Paulino, Niraldo, Sheila Rago Lemos Abreu, Yoshihiro Uto, Daisuke Koyama, Hideko Nagasawa, Hitoshi Hori, Verena M. Dirsch, Angelika M. Vollmar, Amarilis Scremin, and Walter A. Bretz. Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis. European Journal of Pharmacology 587, no. 1-3 (2008): 296-301.
Machado, Joleen Lopes, Anne Karine Martins Assunçao, Mayara Cristina Pinto da Silva, Aramys Silva dos Reis, Graciomar Conceição Costa, Diêgo de Sousa Arruda, Bruno Alves Rocha et al. Brazilian green propolis: anti-inflammatory property by an immunomodulatory activity. Evidence-Based Complementary and Alternative Medicine 2012 (2012).
Shimizu, Kazuo, Hitoshi Ashida, Yukinaga Matsuura, and Kazuki Kanazawa. Antioxidative bioavailability of artepillin C in Brazilian propolis. Archives of biochemistry and biophysics424, no. 2 (2004): 181-188.
Grange, J. M., and R. W. Davey. Antibacterial properties of propolis (bee glue). Journal of the Royal Society of Medicine83, no. 3 (1990): 159-160.
Schmidt J.O., Buchmann S.L. (1992) Other products of the hive, in: Graham J.M. (Ed.), The Hive and the Honey Bee, Hamilton, Illinois, pp. 928–977.
Ghisalberti EL, Jefferies PR, Lanteri R, Matisons J (1978) Constituents of propolis. Experientia 34, 157-158.
Bankova, Vassya. Chemical diversity of propolis and the problem of standardization. Journal of ethnopharmacology100, no. 1-2 (2005): 114-117.
Casteels, Peter, Christophe Ampe, Franciscus Jacobs, and Paul Tempst. Functional and chemical characterization of Hymenoptaecin, an antibacterial polypeptide that is infection-inducible in the honeybee (Apis mellifera). Journal of Biological Chemistry 268, no. 10 (1993): 7044-7054.
Kimoto, Tetsuo, Shigeyuki Arai, Michihiro Kohguchi, Miho Aga, Yutaka Nomura, Mark J. Micallef, Masashi Kurimoto, and Keiichiro Mito. Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis. Cancer detection and prevention 22, no. 6 (1998): 506-515.
Sawicka, Diana, Halina Car, Maria Halina Borawska, and Jacek Nikliński. The anticancer activity of propolis. Folia Histochemica et Cytobiologica 50, no. 1 (2012): 25-37.
Chan, Godfrey Chi-Fung, Ka-Wai Cheung, and Daniel Man-Yuen Sze. The immunomodulatory and anticancer properties of propolis. Clinical Reviews in Allergy & Immunology 44, no. 3 (2013): 262-273.
Sforcin, J. M. Propolis and the immune system: a review. Journal of ethnopharmacology 113, no. 1 (2007): 1-14.
Ghisalberti EL, Jefferies PR, Lanteri R, Matisons J (1978) Constituents of propolis. Experientia 34, 157-158.
Krell, R., 1996. Value-Added products from bee keeping. Milan, FAO Publications.
Gabrys J., et al., 1986. - Free amino acids in bee hive product (propolis) as identified and quantified by gas-liquid chromatography. Pharm. Res. Comm., 18 (6), 513-518.
Iyyam Pillai, S., P. Palsamy, S. Subramanian, and M. Kandaswamy. Wound healing properties of Indian propolis studied on excision wound-induced rats. Pharmaceutical Biology 48, no. 11 (2010): 1198-1206.
Marcucci, M. C. Propolis: chemical composition, biological properties and therapeutic activity. Apidologie 26, no. 2 (1995): 83-99.
Aripov, K. L. A., I. K. Kamilov, and Kh U. Aliev. Effect of propolis on experimental stomach ulcers in rats. Medskii Zh Uzbek 5 (1968): 50-52.
Freitas, S. F., L. Shinohara, J. M. Sforcin, and S. Guimarães. In vitro effects of propolis on Giardia duodenalis trophozoites. Phytomedicine 13, no. 3 (2006): 170-175.
Miyares, C., I. Hollands, C. Castaneda, T. Gonzalez, T. Fragoso, R. Curras, and C. Soria. Clinical trial with a preparation based on propolis "propolisina" in human giardiasis. Acta Gastroenterologica Latinoamericana 18, no. 3 (1988): 195-201.
David, Érica Boarato, Thaís Batista de Carvalho, Clarisse Maria Boni de Oliveira, Silvana Torossian Coradi, José Maurício Sforcin, and Semíramis Guimarães. Characterisation of protease activity in extracellular products secreted by Giardia duodenalis trophozoites treated with propolis. Natural product research 26, no. 4 (2012): 370-374.
Aslan, Ahmet, Muhyittin Temiz, Esin Atik, Gurbuz Polat, Nuray Sahinler, Elmir Besirov, Nedim Aban, and Cem Kaan Parsak. Effectiveness of mesalamine and propolis in experimental colitis. Advances in therapy 24, no. 5 (2007): 1085-1097.
Okamoto, Yoshihiro, Takazumi Hara, Tatsuya Ebato, Takashi Fukui, and Toshiyuki Masuzawa. Brazilian propolis ameliorates trinitrobenzene sulfonic acid-induced colitis in mice by inhibiting Th1 differentiation. International immunopharmacology 16, no. 2 (2013): 178-183.
Gonçalves, Cely Cristina Martins, Luzmarina Hernandes, Ciomar Aparecida Bersani-Amado, Selma Lucy Franco, Joaquim Felipe de Souza Silva, and Maria Raquel Marçal Natali. Use of propolis hydroalcoholic extract to treat colitis experimentally induced in rats by 2, 4, 6-trinitrobenzenesulfonic acid. Evidence-based complementary and alternative medicine 2013 (2013).
Wang, Kai, Xiaolu Jin, Mengmeng You, Wenli Tian, Richard Leu, David Topping, Michael Conlon, Liming Wu, and Fuliang Hu. Dietary propolis ameliorates dextran sulfate sodium-induced colitis and modulates the gut microbiota in rats fed a western diet. Nutrients 9, no. 8 (2017): 875.
Bezerra, Gislaine Barbosa, Luana de Menezes de Souza, Adailma Santana dos Santos, Grace Kelly Melo de Almeida, Marília Trindade Santana Souza, Sandra Lauton Santos, Enilton Aparecido Camargo et al. Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model. Biomedicine & Pharmacotherapy 85 (2017): 687-696.
Metzner, J., Bekermeier, H., Paintz, M., Schneidewind, E., 1979. Zur antimikrobiellen wirksamkeit von propolis und propolisinhaltsstoffen. Pharmazie 34, 97–102.
Khayyal, M. T., M. A. El-Ghazaly, and A. S. El-Khatib. Mechanisms involved in the antiinflammatory effect of propolis extract. Drugs under experimental and clinical research 19, no. 5 (1993): 197-203.
Borrelli, F., P. Maffia, L. Pinto, A. Ianaro, A. Russo, F. Capasso, and A. Ialenti. Phytochemical compounds involved in the anti-inflammatory effect of propolis extract. Fitoterapia73 (2002): S53-S63.
Paulino, Niraldo, Sheila Rago Lemos Abreu, Yoshihiro Uto, Daisuke Koyama, Hideko Nagasawa, Hitoshi Hori, Verena M. Dirsch, Angelika M. Vollmar, Amarilis Scremin, and Walter A. Bretz. Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis. European Journal of Pharmacology 587, no. 1-3 (2008): 296-301.
Ghisalberti, E.L., 1979. Propolis: a review. Bee World 60, 59–84.
Paulino, Niraldo, Andreia Pires Dantas, Vassya Bankova, Daniela Taggliari Longhi, Amarilis Scremin, Solange Lisboa de Castro, and João Batista Calixto. Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle. Journal of Pharmacological Sciences 93, no. 3 (2003): 307-313.
Ledon, N., A. Casaco, R. Gonzalez, N. Merino, A. Gonzalez, and Z. Tolon. Antipsoriatic, anti-inflammatory, and analgesic effects of an extract of red propolis. Zhongguo yao li xue bao= Acta pharmacologica Sinica 18, no. 3 (1997): 274-276.
Kamburoğlu, Kıvanç, and Tuncer Özen. Analgesic effect of Anatolian propolis in mice. Agri 23, no. 2 (2011): 47-50.
Sosnowski, Zenon M. Method for extracting propolis and water soluble dry propolis powder. U.S. Patent 4,382,886, issued May 10, 1983.
Gao, Weina, Jianquan Wu, Jingyu Wei, Lingling Pu, Changjiang Guo, Jijun Yang, Ming Yang, and Haiji Luo. Brazilian green propolis improves immune function in aged mice. Journal of clinical biochemistry and nutrition 55, no. 1 (2014): 7-10.
Moriyasu, J., S. Arai, R. Motoda, and M. Kurimoto. In vitro activation of mouse macrophage by propolis extract powder. Biotherapy 8 (1994): 364-365.
Orsi, R. O., Funari, S. R. C., Soares, A. M. V. C., Calvi, S. A., Oliveira, S. L., Sforcin, J. M., & Bankova, V. (2000). Immunomodulatory action of propolis on macrophage activation. Journal of Venomous Animals and Toxins, 6(2), 205-219.
Kurimoto, Masashi. Isolation and Identification of Compounds from Brazilian Propolis which Enhance Macrophage Spreading and Mobility. (1996).
Sforcin, J. M. Propolis and the immune system: a review. Journal of ethnopharmacology 113, no. 1 (2007): 1-14.
Scheller, S., G. Gazda, G. Pietsz, J. Gabrys, J. Szumlas, L. Eckert, and J. Shani. The ability of ethanol extract of propolis to stimulate plaque formation in immunized mouse spleen cells. Pharmacological research communications 20, no. 4 (1988): 323-328.
Harish, Z., A. Rubinstein, M. Golodner, M. Elmaliah, and Y. Mizrachi. Suppression of HIV-1 replication by propolis and its immunoregulatory effect. Drugs under experimental and clinical research 23, no. 2 (1997): 89-96.
Queiroz, Geisiany Maria de. Estudo fitoquímico, avaliação da atividade antimicrobiana, antioxidante e citotóxica de extrativos de Equisetum hyemale L.(Equisetaceae). (2011): 133-f.
Kubota, Yoko, Keizo Umegaki, Kyoko Kobayashi, Naoko Tanaka, Satomi Kagota, Kazuki Nakamura, Masaru Kunitomo, and Kazumasa Shinozuka. Anti‐hypertensive effects of Brazilian propolis in spontaneously hypertensive rats. Clinical and Experimental Pharmacology and Physiology 31 (2004): S29-S30.
Nader, Manar A., Dina S. El-Agamy, and Ghada M. Suddek. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Archives of Pharmacal Research 33, no. 4 (2010): 637-643.
Fuliang, H. U., H. R. Hepburn, Hongzhuan Xuan, Minli Chen, S. Daya, and S. E. Radloff. Effects of propolis on blood glucose, blood lipid and free radicals in rats with diabetes mellitus. Pharmacological Research 51, no. 2 (2005): 147-152.
Selamoglu Talas, Zeliha. Propolis reduces oxidative stress in l‐NAME‐induced hypertension rats. Cell biochemistry and function 32, no. 2 (2014): 150-154.
Basnet, Purusotam, Katsumichi Matsushige, Koji Hase, Shigetoshi Kadota, and Tsuneo Namba. Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury models. Biological and Pharmaceutical Bulletin 19, no. 11 (1996): 1479-1484.
Banskota, A. H., Y. Tezuka, I. K. Adnyana, E. Ishii, K. Midorikawa, K. Matsushige, and S. Kadota. Hepatoprotective and anti-Helicobacter pylori activities of constituents from Brazilian propolis. Phytomedicine 8, no. 1 (2001): 16-23.
Gonzalez, R., I. Corcho, D. Remirez, S. Rodriguez, O. Ancheta, N. Merino, A. Gonzalez, and C. Pascual. Hepatoprotective effects of propolis extract on carbon tetrachloride‐induced liver injury in rats. Phytotherapy Research 9, no. 2 (1995): 114-117.
González, Ricardo, Diadelys Remirez, Sandra Rodriguez, Addys González, Odelsa Ancheta, Nelson Merino, and Carlos Pascual. Hepatoprotective effects of propolis extract on paracetamol‐induced liver damage in mice. Phytotherapy Research 8, no. 4 (1994): 229-232.
Ates, B., Dogru, M. I., Gul, M., Erdogan, A., Dogru, A. K., et al. (2006) Protective role of caffeic acid phenethyl ester in the liver of rats exposed to cold stress. Fundam. Clin. Pharmacol. 20, 283–289.
Pekmez, H., Kus, I., Colakoglu, N., Ogeturk, M., Ozyurt, H., et al. (2007) The protective effects of caffeic acid phenethyl ester (CAPE) against liver damage induced by cigarette smoke inhalation in rats. Cell Biochem. Funct. 25, 395–400.
Ghisalberti, E.L., 1979. Propolis: a review. Bee World 60, 59–84.
Burdock, G. A. (1998). Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical toxicology, 36(4), 347-363.
Walgrave, Susan E., Erin M. Warshaw, and Lynn A. Glesne. Allergic contact dermatitis from propolis. Dermatitis 16, no. 4 (2005): 209-215.
Wanscher, Birgitte. Contact dermatitis from propolis. British Journal of Dermatology 94, no. 4 (1976): 451-456.
Gulbahar, Okan, Gunseli Ozturk, Nihat Erdem, Ali C. Kazandi, and Ali Kokuludag. Psoriasiform contact dermatitis due to propolis in a beekeeper. Annals of Allergy, Asthma & Immunology 94, no. 4 (2005): 509-511.
Garrido, Fernández S., Alemán E. Arroabarren, Figueroa BE García, Fagoaga E. Goienetxe, Rivera JM Olaguibel, and Purroy AI Tabar. Direct and airborne contact dermatitis from propolis in beekeepers. Contact dermatitis 50, no. 5 (2004): 320.
de Groot, A. C. (2013). Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects. Dermatitis, 24(6), 263-282.
Hausen, Björn M. Evaluation of the main contact allergens in propolis (1995 to 2005). Dermatitis 16, no. 3 (2005): 127-129.