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Propolis

Common Name(s): Propolis , propolis balsam , propolis resin , propolis wax , bee glue , hive dross

Clinical Overview

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Uses of Propolis

Propolis exhibits anti-inflammatory, antitumor, and antioxidant activity, but large, well-designed clinical trials are lacking.

Propolis Dosing

There is no clinical evidence to support specific dosage recommendations for propolis.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Propolis Interactions

None well documented.

Propolis Adverse Reactions

Allergic reactions with skin and mucous membrane irritations have been reported. Sensitization to propolis, long recognized by apiary workers, also has been reported.

Toxicology

Information regarding toxicology is lacking.

Botany

Propolis is a natural resinous product collected from the buds of conifers and other trees by honey bees. It is used by bees to seal walls and strengthen combs of hives as well as to embalm dead invaders. It is a sticky, greenish-brown mass with a slight aromatic odor. 1 , 2 , 3 , 4

History

Propolis has been used as a medicinal agent since ancient times. It was used in folk medicine as early as 300 BC for cosmetic purposes, its anti-inflammatory properties, and for wound healing. It has been used internally and externally, and is believed to possess antibacterial, antiviral, fungicidal, local anesthetic, antiulcer, anti-inflammatory, immunostimulant, hypotensive, and cytostatic properties. 1 , 2 , 3

Chemistry

The composition of propolis varies with its geographic and plant source, as well as with the collection season. 1 , 4 The alcohol extract of propolis is called propolis wax or tincture, with the insoluble residue known as propolis resin. 3 Propolis contains 50% resin and vegetable balsam, 30% wax, 10% essential and aromatic oils, 5% pollen, and 5% other substances including minerals such as magnesium, nickel, iron, calcium, and zinc. 2 , 3

Propolis contains flavonoids such as quercetin, pinocembrin, galangin, and pinobanksin, as well as hydroquinone, caffeic acid, and caffeic acid esters. 2 , 3 A number of other compounds have been identified in propolis from specific geographic sources. 5 , 6 , 7 , 8 , 9



Propolis Uses and Pharmacology

Antimicrobial action

In vitro studies have shown broad spectrum antimicrobial activity of various propolis extracts, 1 , 2 , 3 , 5 , 6 , 9 , 10 , 11 although activity was highest in gram-positive bacteria and yeasts. Synergism with certain antibiotics has been demonstrated. 12

In clinical studies, propolis has been investigated for its activity against Helicobacter pylori , chronic vaginitis, genital herpes, and periodontal and respiratory tract infections. 1 , 13 , 14 , 15 , 16 A clear therapeutic role for propolis is difficult to validate because of variations in antimicrobial action, which are dependent on geographical origin and extraction method employed.

Free radical scavenging

Extracts of propolis have been investigated for their antioxidant properties, with some studies suggesting that the aqueous extract is more effective than the ethanolic, but not consistently so. 1 Phenolic constituents isolated from propolis show more potent free-radical scavenging activity than caffeic acid and vitamins C and E. 1 The antioxidant activity of propolis is considered to be one of the rationales for its proposed antitumor and hepatoprotective activity. 1 , 17 , 18 , 19

Antitumor activity

Antitumor activity of propolis and its chemical constituents has been demonstrated in various animal and in vitro models against Ehrlich carcinomas; colonic, intestinal, hepatocellular, lung, and skin cancer; and leukemia. 1 , 3 , 7 , 8 , 20 , 21 , 22 , 23 , 24 , 25 , 26 However, clinical studies are lacking.

Anti-inflammatory effect

Propolis exhibits anti-inflammatory effects in acute and chronic animal models of inflammation. 2 , 27 The exact mechanism of action is unclear, but in vivo suppression of prostaglandin and leukotriene generation, and suppression of the lipoxygenase pathway of arachidonic acid metabolism have been demonstrated. 1 , 28

A 13% aqueous extract of propolis showed potent dose-related anti-inflammatory activity in rats comparable to the reference standard diclofenac. 29

An in vitro experiment with human cartilage showed caffeic acid phenethyl ester to be more protective than indomethacin, suggesting involvement of free radical scavenging properties. 30

A clinical study of the effect of propolis in asthmatic patients demonstrated a reduction in the frequency of asthma attacks, an increase in ventilatory function, and a decrease in inflammatory indicators (prostaglandins and leukotrienes). 31

Other actions
Immunostimulatory action

Propolis exhibited immunostimulatory and modulatory effects on macrophages in vitro, and increased the ratio of CD4/CD8T cells in mice. 1 , 2

Hepatoprotective effect

Several studies demonstrated a hepatoprotective effect of propolis in rats against acetaminophen-induced liver injury. 1 , 32 The aqueous and ethanolic extracts appear to be effective by including free-radical scavenging. There are no published human trials to date.

Oro-dental use

Propolis is used as a mouthwash, toothpaste, and throat lozenge because of its purported antibacterial and anti-inflammatory properties.

In vitro studies have shown activity against common periodontal pathogens, 2 , 33 with one study suggesting that caffeic acid acts at the cellular level to influence epithelial membrane function against microbes. 34 The use of propolis as a storage medium for teeth following avulsion has been investigated. Teeth stored in propolis demonstrated the highest number of viable cells when compared with milk, saline, and Hanks Balanced Salt Solution . 35

Antihyperglycemic effect

In a small clinical study, propolis mixed with mulberry leaf extract decreased fasting blood sugar levels in patients with type 2 diabetes resistant to sulfonylurea and/or alpha-glucosidase inhibitors. 36

Dosage

There is no clinical evidence to support specific dosage recommendations for propolis. A 13% aqueous solution was used in a clinical study in individuals with asthma. 31 A 5% preparation was used topically in a study on recurrent vaginitis. 14

A study of respiratory tract infection prevention in children used a 50 mg/mL propolis mixture, giving children 1 to 3 years of age 250 mg and children 4 to 5 years of age 375 mg daily for 12 weeks. 16

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

In a study of propolis' effect in mice with Ehrlich carcinoma, an interaction between propolis and bleomycin was noted that resulted in a reduction in survival rate. 37

Adverse Reactions

Propolis is considered relatively nontoxic, possibly because flavonoids are the main chemical constituents. 1 , 2 , 3

Allergic reactions with skin and mucous membrane irritations have been reported, 38 , 39 , 40 , 41 suggesting cautious use in asthmatic or eczematous patients 1 despite a clinical trial conducted in patients with asthma. 31

Sensitization to propolis with cross-sensitivity with balsam of Peru, a common additive in flavoring agents, has been reported. 41 , 42 , 43

Adverse reactions are more common at doses greater than 15 g/day. 2

Toxicology

Information regarding toxicology is lacking.

Bibliography

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3. Burdock GA. Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol . 1998;36:347-363.
4. Bankova V. Chemical diversity of propolis and the problem of standardization. J Ethnopharmacol . 2005;100:114-117.
5. Popova M, Silica S, Kaftanoglu O, Bankova V. Antibacterial activity of Turkish propolis and its qualitative and quantitative chemical composition. Phytomedicine . 2005;12:221-228.
6. Trusheva B, Popova M, Naydenski H, Tsvetkova I, Gregorio Rodriguez J, Bankova V. New polyisoprenylated benzophenones from Venezuelan propolis. Fitoterapia . 2004;75:683-689.
7. Chen CN, Wu CL, Shy HS, Lin JK. Cytotoxic prenylflavanones from Taiwanese propolis. J Nat Prod . 2003;66:503-506.
8. Chen CN, Wu CL, Lin JK. Propolin C from propolis induces apoptosis through activating caspases, Bid and cytochrome c release in human melanoma cells. Biochem Pharmacol . 2004;67:53-66.
9. Abd El Hady FK, Hegazi AG. Egyptian propolis: 2. Chemical composition, antiviral and antimicrobial activities of East Nile Delta propolis. Z Naturforsch [C] . 2002;57:386-394.
10. Kujumgiev A, Tsvetkova I, Serkedjieva Y, Bankova V, Christov R, Popov S. Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethnopharmacol . 1999;64:235-240.
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12. Stepanovic S, Antic N, Dakic I, Svabic-Vlahovic M. In vitro antimicrobial activity of propolis and synergism between propolis and antimicrobial drugs. Microbiol Res . 2003;158:353-357.
13. Nostro A, Cellini L, Di Bartolomeo S, et al. Antibacterial effect of plant extracts against Helicobacter pylori . Phytother Res . 2005;19:198-202.
14. Imhof M, Lipovac M, Kurz Ch, Barta J, Verhoeven HC, Huber JC. Propolis solution for the treatment of chronic vaginitis. Int J Gynaecol Obstet . 2005;89:127-132.
15. Vynograd N, Vynograd I, Sosnowski Z. A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV). Phytomedicine . 2000;7:1-6.
16. Cohen HA, Varsano I, Kahan E, Sarrell EM, Uziel Y. Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study. Arch Pediatr Adolesc Med . 2004;158:217-221.
17. Chopra S, Pillai KK, Husain SZ, Giri DK. Propolis protects against dororubicin-induced myocardiopathy in rats. Exp Mol Pathol . 1995;62:190-198.
18. Pascual C, Gonzalez R, Torricella RG. Scavenging action of propolis extract against oxygen radicals. J Ethnopharmacol . 1994;41:9-13.
19. Scheller S, Wilczok T, Imielski S, Krol W, Gabrys J, Shani J. Free radical scavenging by ethanol extract of propolis. Int J Radiat Biol . 1990;57:461-465.
20. Orsolic N, Knezevic AH, Sver L, Terzic S, Basic I. Immunomodulatory and antimetastatic action of propolis and related polyphenolic compounds. J Ethnopharmacol . 2004;94:307-315.
21. Aso K, Kanno S, Tadano T, Satoh S, Ishikawa M. Inhibitory effect of propolis on the growth of human leukemia U937. Biol Pharm Bull . 2004;27:727-730.
22. Woo KJ, Jeong YJ, Park JW, Kwon TK. Chrysin-induced apoptosis is mediated through caspase activation and Ak tinactivation in U937 leukemia cells. Biochem Biophys Res Commun . 2004;325:1215-1222.
23. Russo A, Cardile V, Sanchez F, Troncoso N, Vanella A, Garbarino JA. Chilean propolis: antioxidant activity and antiproliferative action in human tumor cell lines. Life Sci . 2004;76:545-558.
24. Mishima S, Narita Y, Chikamatsu S, et al. Effects of propolis on cell growth and gene expression in HL-60 cells. J Ethnopharmacol . 2005;99:5-11.
25. Cuesta-Rubio O, Frontana-Uribe BA, Ramirez-Apan T, Cardenas J. Polyisoprenylated benzophenones in cuban propolis; biological activity of nemorosone. Z Naturforsch [C] . 2002;57:372-378.
26. Liao HF, Chen YY, Liu JJ, et al. Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and metastasis. J Agric Food Chem . 2003;51:7907-7912.
27. Borrelli F, Maffia P, Pinto L, et al. Phytochemical compounds involved in the anti-inflammatory effect of propolis extract. Fitoterapia . 2002;73(suppl.1):S53-S63.
28. Mirzoeva OK, Calder PC. The effect of propolis and its components on eicosanoid production during the inflammatory response. Prostaglandins Leukot Essent Fatty Acids . 1996;55:441-449.
29. Khayyal MT, el-Ghazaly MA, el-Khatib AS. Mechanisms involved in the antiinflammatory effect of propolis extract. Drugs Exp Clin Res . 1993;19:197-203.
30. Cardile V, Panico A, Gentile B, Borrelli F, Russo A. Effect of propolis on human cartilage and chondrocytes. Life Sci . 2003;73:1027-1035.
31. Khayyal MT, el-Ghazaly MA, el-Khatib AS, Hatem AM, de Vries PJ, el-Shafei S, Khattab MM. A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patients. Fundam Clin Pharmacol . 2003;17:93-102.
32. El-Khatib AS, Agha AM, Mahran LG, Khayyal MT. Prophylactic effect of aqueous propolis extract against acute experimental hepatotxicity in vivo. Z Naturforsch [C] . 2002;57:379-385.
33. Santos FA, Bastos EM, Maia AB, et al. Brazilian propolis: physicochemical properties, plant origin and antibacterial activity on periodontopathogens. Phytother Res . 2003;17:285-289.
34. Shieh DB, Yang SR, Shi XY, Wu YN, Wu SN. Properties of BK(Ca) channels in oral keratinocytes. J Dent Res . 2005;84:468-473.
35. Martin MP, Pileggi R. A quantitative analysis of Propolis: a promising new storage media following avulsion. Dent Traumatol . 2004;20:85-89.
36. Murata K, Yatsunami K, Fukuda E, et al. Antihyperglycemic effects of propolis mixed with mulberry leaf extract on patients with type 2 diabetes. Altern Ther Health Med . 2004;10:78-79.
37. Scheller S, Gazda G, Krol W, et al. The ability of ethanolic extract of propolis (EEP) to protect mice against gamma irradiation. Z Naturforsch [C] . 1989;44:1049-1052.
38. Pincelli C, Motolese A, Pincelli L. Contact dermatitis from propolis. Contact Dermatitis . 1984;11:49.
39. Hay KD, Greig DE. Propolis allergy: a cause of oral mucositis with ulceration. Oral Surg Oral Med Oral Pathol . 1990;70:584-586.
40. Gulbahar O, Ozturk G, Erdem N, Kazandi AC, Kokuludag A. Psoriasiform contact dermatitis due to propolis in a beekeeper. Ann Allergy Asthma Immunol . 2005;94:509-511.
41. Ting PT, Silver S. Allergic contact dermatitis to propolis. J Drugs Dermatol . 2004;3:685-686.
42. Hsu CY, Chiang WC, Weng TI, Chen WJ, Yuan A. Laryngeal edema and anaphalactic shock after topical propolis use for acute pharyngitis. Am J Emerg Med . 2004;22:432-433.
43. Giusti F, Miglietta R, Pepe P, Seidenari S. Sensitization to propolis in 1255 children undergoing patch testing. Contact Dermatitis . 2004;51:255-258.

 

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