Propolis

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

Uses

Propolis exhibits antimicrobial action against gram-positive bacteria, yeasts, and some viruses. Commonly used in oral and dental preparations, propolis may have a role in reducing caries and oral ulcers and in promoting the health of injured teeth. Cytotoxicity of propolis and its chemical constituents has been demonstrated in various animal and in vitro models; however, clinical studies in cancer are lacking. Immune system effects, antioxidant actions, and effects on the cardiovascular system have also been described.

Dosing

There is limited 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.

Interactions

None well documented.

Adverse Reactions

Allergic reactions with skin and mucous membrane irritations have been reported. Sensitization to propolis, long recognized by apiary workers, has also 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 honeybees. 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, for 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 , 5 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 , 5

Propolis contains flavonoids, including quercetin, pinocembrin, galangin, and pinobanksin, as well as hydroquinone, caffeic acid, and caffeic acid esters. 2 , 3 , 5 A number of other compounds have been identified in propolis from specific geographic sources. 6 , 7 , 8 , 9 , 10

Uses and Pharmacology

Few high quality clinical trials have been undertaken. Researchers disagree over the importance of plant source and geographical variation on the spectrum of efficacy for propolis extracts. 4 , 11 , 12 , 13

Antimicrobial action

In vitro studies have shown broad-spectrum antimicrobial activity of various propolis extracts, 1 , 2 , 3 , 6 , 7 , 9 , 14 , 15 , 16 , 17 although activity was highest in gram-positive bacteria and yeasts. 5 , 11 , 17 , 18 , 19 Synergism with several antibiotics has been demonstrated. 20 Antiviral action has also been demonstrated in animal and in vitro experiments, including activity against herpes simplex viruses types 1 and 2 and influenza viruses. 5 , 21 , 22 , 23 In clinical studies, propolis has been investigated for its activity against chronic vaginitis, genital herpes, and periodontal and respiratory tract infections; however, these studies are either unblinded, nonrandomized, or not compared with standard therapy, making definitive statements about efficacy difficult. 1 , 12 , 24 , 25 , 26 , 27 One pilot study (N = 18) investigated the effect of an ethanolic preparation of Brazilian green propolis on Helicobacter pylori . 28 Twenty drops of the preparation taken 3 times a day for 7 days was not effective in eradicating H. pylori , despite in vitro studies showing that it inhibited bacterial growth. 28 The researchers suggested that a trial with an increased dosage was warranted.

Antioxidant activity

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 1 rationale for its proposed antitumor and hepatoprotective activity. 1 , 29 , 30 , 31

A reduction in exercise-induced oxidative stress was demonstrated in vitro for caffeic acid phenethyl ester, while a protective effect on ischemia/reperfusion injury in the brain and spinal cord of rats was also demonstrated. 32 , 33

A clinical study among healthy volunteers found no effect on oxidative status in women. In men, decreases in plasma malondialdehyde were observed at 15 days, and increased superoxide dismutase activity was observed at 30 days of treatment with daily powdered propolis containing 48.75 mg of flavonoids. 34

Cancer

Cytotoxic activity of propolis and its chemical constituents has been demonstrated in breast, cervical, colonic, intestinal, liver, lung, prostate, and skin cancers and leukemia in various animal and in vitro models. 1 , 3 , 8 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 However, clinical studies are lacking.

Antiangiogenic effects have been demonstrated, as well as augmentation of natural defense mechanisms such as tumor necrosis factor and caspase pathways, and increased apoptosis by propolis and its constituents. 5 , 46 , 47 , 48 , 49 Selective binding to human estrogen receptor beta (but not alpha), with no estrogenic effect on estrogen receptor-positive breast cancer cells, has been demonstrated in female rats. 50 An aqueous extract of propolis was not protective against induced hepatocarcinogenesis in a study in rats. 51

Prevention or reduction of hepatotoxicity due to chemotherapy has been demonstrated by propolis extracts in animal experiments. 5 , 52

Cardiovascular system effects

Antihypertensive, hypoglycemic, and antidyslipidemic effects have been described for propolis. In rats and in 1 clinical trial, an improved lipid profile was achieved in the serum and liver with administration of propolis. 5 , 53 , 54 Another clinical study among healthy volunteers found no effect on plasma lipid or glucose profile. 34 Decreased hyperglycemia has been demonstrated in a small clinical study with mulberry and propolis in patients with resistant type 2 diabetes. 54 A relaxant vasodilatory effect has been demonstrated on rat and porcine aorta and coronary artery segments, while the ethanolic fraction of propolis was hypotensive in rats. 5 , 55 , 56

Immune system effects (eg, anti-inflammatory, wound healing)

A review of the effects of propolis extracts and individual chemical components has been published; however, clinical studies are limited. 13 Effects on the immune system include macrophage activation, modulation of lymphocyte and antibody proliferation, cytokine production, and downregulation of transcription factors. Observed antitumor effects have been attributed to an enhanced immune response. 5 , 13 , 57 , 58 , 59

Both orally administered propolis and topical applications improved wound healing, with increased wound closure rates and decreased inflammation in rodents. 60 , 61

Propolis exhibits anti-inflammatory effects in acute and chronic animal models. 5 , 62 The exact mechanism of action is unclear, but in vivo suppression of prostaglandin and leukotriene generation, as well as suppression of the lipoxygenase pathway of arachidonic acid metabolism have been demonstrated. 1 , 63 A 13% aqueous extract of propolis showed potent dose-related anti-inflammatory activity in rats comparable with the reference standard diclofenac, 64 while an in vitro experiment with human cartilage showed caffeic acid phenethyl ester to be more protective than indomethacin. 65 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. 66

Orodental use

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

In vitro studies have shown activity against common periodontal pathogens, including Candida species and the Streptococci mutans group, 2 , 12 , 67 with 1 study suggesting that caffeic acid acts at the cellular level to influence epithelial membrane function against microbes. 68 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 Hank's Balanced Salt Solution . 69 , 70 Similarly, propolis and caffeic acid phenethyl ester have been investigated for effect on traumatic injury to the teeth and activities on osteoclast maturation. 71 , 72

Clinical trials have shown the efficacy of propolis 500 mg in reducing the recurrence of aphthous stomatitis 73 and propolis mouthwashes in reducing caries indicators (total bacterial and Streptococcus mutans counts). 12

Other actions

Several studies demonstrated a hepatoprotective effect of propolis in rats against acetaminophen-induced liver injury, as well as injury due to alcohol and carbon-tetrachloride. 1 , 5 , 74 The aqueous and ethanolic extracts appear to be effective by including free-radical scavenging. There are no published human trials to date.

A protective effect against chronic alcohol-induced corneal damage has been demonstrated in rats. 75

Dosage

There is limited clinical evidence to support specific dosage recommendations for propolis. Dental preparations containing propolis are commercially available, including oral gels and mouthwashes, despite equivocal results in clinical studies. 12

A 13% aqueous solution was used orally in a clinical study in individuals with asthma. 66 A 5% preparation was used topically in a study on recurrent vaginitis. 25

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. 27 In a small pilot study (N = 18), 20 drops of an ethanolic preparation of Brazilian green propolis taken 3 times a day for 7 days was not effective in eradicating H. pylori , despite in vitro studies suggesting inhibition of bacterial growth. 28

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. 76

Interactions

Clinical information is limited. 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. 77 , 78

Adverse Reactions

Propolis is considered to be relatively nontoxic. 1 , 2 , 3 Allergic reactions with skin and mucous membrane irritations have been commonly reported in apiary workers, 79 , 80 , 81 , 82 and a multicenter study reported a prevalence for positive patch tests of 1.9%. Other reports estimate the prevalence to be even higher 83 ; therefore, cautious use in asthmatic or eczematous patients is advised, despite a potentially beneficial clinical trial in patients with asthma. 1 , 66 Sensitization to propolis with cross-sensitivity to balsam of Peru, a common additive in flavoring agents, has been reported. 82 , 84 , 85

Adverse reactions are more common at doses greater than 15 g/day, 2 although a trial using 20 drops of an ethanolic preparation of Brazilian green propolis taken 3 times a day for 7 days resulted in reports of mild nausea and epigastric pain in some participants. 28

Toxicology

Information regarding toxicology is lacking. The median lethal dose for mice is estimated to be between 2 to 7.3 g/kg and extrapolated to a safe level in humans of propolis 70 mg/day. 3

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