Propolis, a resin-derived bee product, is relatively safe and has antimicrobial properties. Primarily used topically, it can cause contact dermatitis, especially in those sensitive to Balsam of Peru.
[DM ] Letter Key
Description
Propolis, or "bee glue," is an adhesive, resinous substance used by honeybees in building and sealing a hive. Plant resins are masticated (thus acquiring salivary enzymes) and mixed with beeswax; the resulting mixture is used to repair holes and smooth interior walls. Although the precise composition depends on the source, propolis usually contains 50% resin and vegetable balsam, 30% wax, 10% essential and aromatic oils, 5% pollen, and 5% other (1). The proportion of resins to beeswax varies substantially and may be affected by the use the propolis is put to and the local availability of resins. Propolis contains hydroquinone (0.1%), caffeic acid and its esters (2% to 20%), and quercetin (less than 0.1% to 0.7%) (all of these are in much smaller quantities than in dietary sources). Propolis may be an unintended additive in beeswax and honey.
Mechanisms/Pharmacokinetics
Neither mechanism of action nor pharmacokinetics has been delineated. Flavonoids are the most likely active ingredients in propolis. Flavonoids inhibit a variety of enzymes, and propolis has been shown to inhibit glycosyltransferases, myeloperoxidase, ornithine decarboxylase, lipoxygenase, tyrosine protein kinase, and arachidonic acid metabolism.
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[CAO ] Letter Key
Clinical Trials
- Ocular herpes
- One study tested ocular propolis films in 35 patients with postherpetic trophic keratitis and in 20 with postherpetic nebulae (2). Films were applied behind the lower eyelid before bed for 10 to 15 days. Compared with controls, propolis-treated patients recovered nearly twice as fast (7.6 days, compared with 14.1 days in the placebo group).
- Dental plaque inhibition
- A double-blind study comparing a propolis-containing mouthwash with a positive control (chlorhexidine) and a negative control found that the chlorhexidine mouthrinse was significantly better than the others; there was no significant difference between the propolis-containing mouthrinse and the negative control (3).
- Another study tested propolis and honey against oral bacteria in 10 volunteers (an in vitro study was also done). Propolis demonstrated an antibacterial effect on oral streptococci both in vitro and clinically, by reducing salivary bacterial counts (4).
Animal/in Vitro Evidence
- Anti-tumor effects
- A component of propolis, caffeic acid phenethyl ester (CAPE), applied topically to CD-1 mice, reduced the number and size of chemically-induced skin papillomas in a dose-dependent manner. In an in vitro test, CAPE added to cultured HeLa cells (a cervical cancer line) inhibited the synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in a dose-dependent manner (5). CAPE appears to be selectively cytotoxic to tumor cells and virally transformed cells without being cytotoxic to normal cells. Low doses of CAPE (0.1 to 6.5 nmol/topical treatment) in SENCAR mice inhibit several oxidative tumor-promoting actions, including myeloperoxidase activity (indicative of polymorphonuclear leukocyte infiltration into tissues), hydrogen peroxide production, and formation of oxidized bases in epidermal DNA. At higher doses, edema and ornithine decarboxylase induction was inhibited (6).
- Dietary caffeic acid esters inhibit the growth of cultured colon cancer cells (7) and (in a dietary dose of 600 ppm) inhibited aberrant crypt foci formation in F344 rats (8). Aberrant crypt foci are precursor lesions for colon cancer. A diet containing 750 ppm phenylether-3-methyl caffeate resulted in a significant decrease in adenocarcinomas of the colon as well as a decrease in colon tumor volume (9).
- Two caffeic acid esters were tested on azoxymethane-induced biochemical changes. One of these esters, phenylethyl caffeate (PEC) (present in honey and in propolis and also synthesized), significantly inhibited azoxymethane-induced ornithine decarboxylase and tyrosine protein kinase activities in liver and colon; PEC also suppressed lipooxygenase metabolites but had no effect on cyclooxygenase metabolism (8). The caffeic acid ester methyl caffeate was far less active.
- Antioxidant effects
- CAPE inhibited hydrogen peroxide production in bovine lenses exposed to an oxidizing agent. This effect could theoretically decrease cataract development (6).
- An aqueous extract of propolis as well as propol (a phenolic component), inhibited Cu2+ initiated low density lipoprotein (LDL) oxidation; in addition, antiapoptotic action was demonstrated in macrophages exposed to minimally modified LDL (10).
- Antimicrobial effects
- Propolis extracts and constituents have been shown to have antibacterial activity against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus viridans, Corynebacterium diphtheria, Escherichia coli, Salmonella typhi, Salmonella paratyphi, and Toxoplasma gondii (1). An ethanolic extract of propolis was shown to have a marked synergistic effect on antibacterial effects of streptomycin and cloxacillin and a moderate synergistic effect on penicillin G, doxycycline, streptomycin, chloramphenicol, cefradine, and polymixin B; no effect was noted on ampicillin (11).
- Although bactericidal against many strains of Mycobacteria, propolis has no effect on Mycobacterium tuberculosis.
- Propolis appears to have no activity against Entamoeba histolytica in vitro and was effective in vivo against T. gondii and Trichomonas vaginalis only at extremely high doses (in one experiment, survival of trichomonas was extended at lower doses) (1). An in vivo experiment in mice infected with Trypanosoma cruzi found no effect on parasitemia kinetics or survival rate (12).
- Antifungal activity has been demonstrated against species of Candida, Saccharomyces, Cryptococcus neoformans, Histoplasma capsulatum, and several species of Trichosporon and Microsporum (1). An in vitro study that compared different extraction methods found that propolis extracts were particularly effective against Sarcinia lutea, Candida albicans, Rhodotorula glutinis, Schizosaccharamyces pombe and various dermatophytes (13). Solvents made a difference. Edible oil extractions were most active, glycerine solutions were the most variable, and ethanol and propylene glycol solutions afforded long-acting inhibition of affected organisms.
- Propolis also appears to have antiviral activity. In vitro, propolis suppresses replication of HIV-1, abolishing syncytium formation at 4.5 µg/mL; p24 antigen production was decreased in a concentration-dependent manner (14). Activity has been demonstrated against herpes simplex virus 1 and 2, adenovirus type 2, vesicular stomatitis virus, and poliovirus type 2. Fractions and isolates of propolis have shown activity against influenza viruses A and B, vaccinia virus, Newcastle disease virus, and a strain of influenza A (1).
- In mice, a water-soluble derivative of propolis was found to induce significant nonspecific host protection against experimental infection with gram-negative pathogens; macrophage activation is suggested as a possible mechanism (15).
- Hepatoprotective effects
- In animals, propolis reduces pathologic liver changes caused by acetaminophen (1). Cuban red propolis protects against galactosamine-induced hepatitis in rats (16). A dose-related effect of aqueous propolis extract was found against hepatotoxicity induced by carbon tetrachloride in liver-cell suspensions (17); a histopathologic study in rats also showed a reduction in carbon tetrachloride-induced hepatotoxicity (18).
- Cardioprotective effects
- In rats, propolis (50 to 100 mg/kg i.p. daily × 5 days) reduced doxorubicin-induced cardiomyopathy, as assessed by histopathology and levels of creatine phosphokinase, malondialdehyde, and glutathione (19).
- Antiinflammatory effects
- An orally administered 13% aqueous extract of propolis (1, 5, and 10 ml/kg) reduced carrageenan-induced rat paw edema and adjuvant-induced arthritis in rats (20). In another experiment, aqueous extract of propolis (5 ml/kg administered orally) reduced carrageenan-induced rat paw edema after whole body gamma irradiation (which exaggerates the inflammatory response) (21). An in vivo study showed that dietary propolis suppressed the lipoxygenase pathway of arachidonic acid metabolism during inflammation (22).
Other Claimed Benefits/Actions
- Antiseptic
- Antifungal
- Antiinflammatory
- Antioxidant
- Anesthetic
- Rheumatism
- Sprains
- Topical: wound healing, burns, leg ulcers, herpes ulcers, pruritus ani, antifungal, and beauty creams
- Gingivitis, stomatitis, and cheilitis
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[ACDT ] Letter Key
Adverse Reactions
Propolis is an allergen and has caused numerous cases of contact dermatitis (23). The allergenic compound may be poplar bud constituents and is most likely the caffeic acid ester, 1,1-dimethylyallyl caffeic acid ester (24) (see questions and answers).
Contraindications
Allergy to Balsam of Peru, which is a resin, similar to benzoin, formed by the Peru balsam tree (Myroxylon pereirae); it is used in topical antiseptics and skin protectants.
Drug Interactions
None identified
Animal Toxicity
Oral LD50 of propolis extract in the mouse has been reported as greater than 7,340 mg/kg by one researcher and 2,050 mg/kg by another researcher. In mice, 700 mg/kg administered orally was reported to be well tolerated; mice were monitored for 48 hours (1).
In a chronic dosing study, Wistar rats received an alcoholic extract of propolis in drinking water at a dose of 1,875 mg/kg/day for 30 days or 2,470 mg/kg/day for 60 days. Compared with controls, no changes were noted in clinical appearance, behavior, urine output, body weight, or mortality (1). No treatment-related histologic changes were noted in either group. No adverse effects were noted in mice treated with 1,400 mg/kg/day for 90 days (1).
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No information is available on oral dosing in humans. Burdock notes that if the no-effect level in mice is extrapolated to humans and reduced a thousand-fold to account for the lack of chronic toxicity studies, 1.4 mg/kg/day (approximately 70 mg/day) should be safe in humans (1).
Mode of Administration
Topical (most popular): ointments, lotions, solutions
Personal products: toothpaste, dental floss, mouthwash, cosmetic products
Oral: capsules, usually 50 mg/capsule, powder, or chewing gum
Q: Is there cross-reactivity between pollen allergy and propolis allergy?
A: Most people allergic to propolis are not allergic to pollen. Propolis is gathered from plant resins, not pollen (although propolis may contain some pollen, it is not a large amount). People sensitive to propolis are most commonly sensitive to plant resins, including Balsam of Peru. Some are also sensitive to essential oils, cinnamic acids and aldehydes, or beeswax (1).
Q: Is populus the same thing as propolis?
A: No, but they are similar. Populus is an oleoresin used as a flavoring agent for alcoholic beverages. It comes from resinous material in poplar buds (Populus species). The poplar is popular as a resin source for bees, so it is no surprise that populus and propolis are chemically very similar (1).
Q: What else is propolis used for?
A: The use of propolis by humans dates to 300 BC. Stradivari reportedly used propolis as an ingredient in the varnish of his stringed instruments, and it is sometimes used today in the repair of accordions and in rosin for stringed instruments. It has been proposed as a chemical preservative in meat products (1).