Propolis

What is propolis

Propolis is a resinous substance or “bee glue” synthesized by honeybees (Apis species) using products present on floral buds, gems, and vegetable cuts 1). The word “propolis” is derived from Greek to mean defense for “pro” and city or community for “polis”, or the beehive, in other words 2). Bees collect resins from buds, exudates and other parts of plants, mix them with their own salivary enzymes and beeswax which creates propolis 3). Propolis is composed of a mixture of different plants parts and molecules secreted by bees 4). Propolis is composed mainly of resin (50%), wax (30%), essential oils (10%), pollen (5%), and other organic compounds (5%) 5). Propolis functions in sealing holes and cracks and for the reconstruction of the beehive. Propolis is also used for smoothing the inner surface of the beehive, retaining the hive’s internal temperature (35°C), preventing weathering and invasion by predators 6). Furthermore, propolis hardens the cell wall and contributes to an aseptic internal environment. Propolis generally becomes soft and sticky upon heating 7). Propolis also possesses a pleasant smell.

The important organic compounds present in propolis are phenolic compounds, esters, flavonoids, terpenes, beta-steroids, aromatic aldehydes, and alcohols 8). Twelve different flavonoids, namely, pinocembrin, acacetin, chrysin, rutin, luteolin, kaempferol, apigenin, myricetin, catechin, naringenin, galangin, and quercetin; two phenolic acids, caffeic acid and cinnamic acid; and one stilbene derivative called resveratrol have been detected in propolis extracts by capillary zone electrophoresis 9). Propolis also contains important vitamins, such as vitamins B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine), C (ascorbic acid), and vitamin E and useful minerals such as magnesium (Mg), calcium (Ca), potassium (K), sodium (Na), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe). A few enzymes, such as succinic dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and acid phosphatase, are also present in propolis 10).

Besides being used as a material for repair, isolation, fixation, and microbiological protection of bee hives, its use as a therapeutic for several diseases has been reported 11). Propolis and its extracts have numerous applications in treating various diseases due to its antiseptic, anti-inflammatory, antioxidant, antibacterial, antimycotic, antifungal, antiulcer, anticancer, and immunomodulatory properties. Green propolis contains a significant amount of Artepillin C, a cinnamic acid derivative 12). Artepillin C acts as an anti-inflammatory and anti-bacterial component when combined with other compounds present in green propolis 13). When propolis was first isolated and identified, it was found to have a significant anti-bacterial potential 14). The anti-bacterial action of propolis is mainly demonstrated on Gram-positive bacteria 15) and has been tested as a major component of many pharmacological compounds used for various purposes, such as wound healing, anti-inflammatory action, and anti-bacterial activities in lab rats 16).

Another type of propolis comes from stingless bees (e.g., Melipona mondury, Melipona scutellaris) and it is called geopropolis. Geopropolis is very similar to propolis produced by bees belonging to Apis spp. in both composition and biological activity 17). Torres et al. 18) in their study compared two ethanolic extracts of propolis collected from a stingless species of bees, Melipona quadrifasciata and Tetragonisca angustula. The study showed the more significant activity of geopropolis extracts against Gram-positive bacteria (Staphylococcus aureus MSSA and MRSA, Enterococcus faecalis) than Gram-negative (Klebsiella pneumoniae, Escherichia coli). From the two geopropolis which were analyzed, the Melipona species was more effective 19).

Propolis chemical compounds

The chemical composition of propolis is closely related to the resins and balsams of plant sources used to produce it. Along with the progress of research, more than 300 chemical components of propolis have been identified 20). The main groups of chemical compounds found to be present in propolis except resins are waxes, polyphenols (phenolic acids, flavonoids) and terpenoids. The activity of propolis depends on chemical composition and is different in individual countries.

Polyphenols and terpenoids are also considered to be the most active 21). The flavonoid group includes chrysin, pinocembrin, apigenin, galangin, kaempferol, quercetin, tectochrysin, pinostrobin and others (see Figure 1). Another critical group of compounds of propolis are aromatic acids, among which the most often occur in ferulic, cinnamic, caffeic, benzoic, salicylic and p-cumaric acids 22). In Polish propolis, the content of flavonoid compounds ranged from 6.2 to 18.8%. Among the flavonoids, the highest amounts were pinocembrin (mean 4.7%), pinobenchin (mean 3.1%), galangin (mean 2.2%) and chrysin (mean 2.1%) 23). In addition, propolis also includes other phenolic compounds (e.g., artepillin C), and terpenes (terpineol, camphor, geraniol, nerol, farnesol) which are responsible for its characteristic fragrance 24). Caffeic acid phenethyl ester (CAPE) is considered an anti-obesity agent with beneficial effects on inflammation and diabetes 25). CAPE reduced insulin resistance in diabetic mice and in hepatic cell culture 26). Chrysin, another component of propolis, also has antidiabetic properties 27). In propolis, micro and macroelements (manganese, iron, silicon, magnesium, zinc, selenium, calcium, potassium, sodium, copper) and vitamins B1, B2, B6, C and E can be found 28). This diversity of the chemical composition gives propolis an additional advantage as an antibacterial agent. The combination of many active ingredients and their presence in various proportions prevents the bacterial resistance from occurring 29).

Figure 1. Important bioactive compounds in propolis, honey and royal jelly.

Important bioactive compounds in propolis, honey and royal jelly
[Source 30) ]

Figure 2. Biological activities of propolis

Biological activities of propolis
[Source 31) ]

What are health benefits of propolis?

Propolis has been reported to have various health benefits related to gastrointestinal disorders, allergies, and gynecological, oral, and dermatological problems.

Propolis is possibly effective for:

  • Diabetes. Research shows that taking propolis may improve blood sugar control by a small amount in people with diabetes. But it doesn’t seem to affect insulin levels or improve insulin resistance.
  • Cold sores (herpes labialis). Most research shows that applying an ointment or cream containing 0.5% to 3% propolis five times daily helps cold sores to heal faster and reduces pain.
  • Swelling (inflammation) and sores inside the mouth (oral mucositis). Most research shows that rinsing the mouth with a propolis mouth rinse helps heal sores caused by cancer drugs or dentures.

Insufficient evidence to rate effectiveness for:

  • Prone to allergies and allergic reactions (atopic disease). Early research shows that taking propolis while nursing a newborn infant doesn’t seem to reduce the child’s risk of developing allergies at one year of age.
  • Burns. Early research shows that applying propolis to the skin every 3 days might help treat minor burns and prevent infections.
  • Canker sores. Early research shows that taking propolis by mouth daily for 6-13 months reduces canker sore outbreaks.
  • A painful disease transmitted by mosquitos (dengue fever). Research shows that taking propolis helps people with dengue fever leave the hospital faster. It is not known if propolis helps with symptoms of dengue fever.
  • Foot sores in people with diabetes. Early research shows that applying a propolis ointment to sores on the feet of people with diabetes might help the sores to heal faster.
  • Genital herpes. Early research shows that applying a 3% propolis ointment four times daily for 10 days might improve healing of lesions in people with genital herpes. Some research suggests that it might heal lesions faster and more completely than the conventional treatment 5% acyclovir ointment.
  • A mild form of gum disease (gingivitis). Early research suggests that using propolis in a gel or a rinse might help prevent or reduce signs of gum disease.
  • A digestive tract infection that can lead to ulcers (Helicobacter pylori or H. pylori). Early research shows that taking 60 drops of a preparation containing Brazilian green propolis daily for 7 days does not reduce H. pylori infection.
  • Infection of the intestines by parasites. Early research suggests that taking a 30% propolis extract for 5 days can cure giardiasis in more people than the drug tinidazole.
  • Thrush. Early research suggests that using Brazilian green propolis extract four times daily for 7 days can prevent oral thrush in people with dentures.
  • A serious gum infection (periodontitis). Early research shows that deeply rinsing the gums with a propolis extract solution decreases bleeding of gums in people with periodontitis. Taking propolis by mouth helps to prevent loose teeth in people with this condition. But taking propolis by mouth doesn’t seem to help with plaque or bleeding.
  • Athlete’s foot (Tinea pedis). Early research shows that applying Brazilian green propolis to the skin decreases itching, peeling, and redness in students with athlete’s foot.
  • Upper airway infection. There is some early evidence that propolis might help prevent or reduce the duration of common colds and other upper airway infections.
  • Swelling (inflammation) of the vagina (vaginitis). Early research suggests that applying a 5% propolis solution vaginally for 7 days can reduce symptoms and improve quality of life in people with vaginal swelling.
  • Warts. Early research shows that taking propolis by mouth daily for up to 3 months cures warts in some people with plane and common warts. However, propolis does not seem to treat plantar warts.
  • Wound healing. Early research shows that using a propolis mouth rinse five times daily for 1 week might improve healing and reduce pain and swelling after mouth surgery. However, if people are already using a special dressing after dental surgery, using a propolis solution in the mouth does not seem to offer additional benefit.
  • Improving immune response.
  • Infections.
  • Infections of the kidney, bladder, or urethra (urinary tract infections or UTIs).
  • Inflammation.
  • Nose and throat cancer.
  • Stomach and intestinal disorders.
  • Tuberculosis.
  • Ulcers.
  • Other conditions.

More evidence is needed to rate propolis for these uses.

Table 1. Propolis health benefits

Health benefitsPropolis activityType of studiesAuthors
Gastrointestinal disorderAntiparasiticHumansFreitas et al. 2006 32)
AntiulcerationAnimalsPaulino et al. 2015 33)
Gynecological careAntifungalHumanImhof et al. 2005 34)
Antifungal and antibiofilmHumanCapoci et al. 2015 35)
Oral healthAntibacterialLaboratoryPereira et al. 2011 36)
Daily mouthwashHumanJain et al. 2014 37)
Toothpaste disinfectionLaboratoryBertolini et al. 2012 38)
Toothpaste against gingivitisHumanSkaba et al. 2013 39)
Oral therapeutic agentHumanPereira et al. 2011 40)
Cancer treatmentAnti-breast cancerHumanXuan et al. 2014 41)
Antimelanoma cancerAnimalsBenguedouar et al. 2015 42)
Anti-lung cancerHumanDemir et al. 2016 43)
Skin careAcne vulgarisHumanAli et al. 2015 44)
Collagen metabolismAnimalsOlczyk et al. 2014 45)
Diabetic foot ulcerHumanHenshaw et al. 2014 46)
[Source 47) ]

Gastrointestinal disorder

Infection with parasites usually occurs upon contact with an infected surface. The symptoms of parasitic infection of the gastrointestinal tract include abdominal pain, diarrhea, bloating, and nausea. Propolis has been reported to have several biological activities including anticancer, antioxidant, and anti-inflammatory activities (see Figure 2). There are a few studies that reported the clinical use of propolis in the treatment of viral infections 48). In one study, the test tube effect of propolis ethanolic extract on the growth and adherence of Giardia duodenalis trophozoites was evaluated 49). Propolis was shown to inhibit growth and adherence of the trophozoites. It also promoted the detachment of these parasitic organisms. Its efficacy against giardiasis has also been reported in a clinical study whereby children and adults with giardiasis-given propolis showed a cure rate between 52% and 60%, whereas those given the conventional drug showed a 40% cure rate. Another experimental study showed that propolis has antihistaminergic, anti-inflammatory, antiacid, and anti-H. pylori activities that can be used to treat gastric ulceration 50).

Gynecological disorder

Widespread causes of indicative vaginitis are bacterial vaginosis and vulvovaginal candidiasis. The depletion of Lactobacillus spp. in the vagina is a distinguished feature of vaginal infections. The infection is accompanied by an overgrowth of vaginal pathogens such as yeast-like fungi and an elevated vaginal pH. Diabetes patients are more prone to having vaginal infections caused by Candida albicans. A study conducted on the application of 5% aqueous propolis solution resulted in an improvement in vaginal well-being 51). In addition to providing antibiotic and antimycotic actions, propolis provides early symptomatic relief due to its anesthetic properties. Thus, propolis may be used for Recurrent Vulvovaginal Candidiasis and can be an alternative option for patients who are unable to take antibiotics due to a concurrent pharmacological treatment. The effectiveness of propolis against conventional antifungal nystatin has shown satisfactory results. Propolis extract solution also show low toxicity in human cells and can be an alternative treatment for chronic vaginitis. In addition, propolis extract solution has antifungal properties and it can be used as antibiofilm material for recurrent vulvovaginal candidiasis to counteract biofilm growth of Candida albicans and resistance in antifungal drug 52).

Oral health

The oral cavity has an abundant bacterial microflora and excessive bacterial growth may lead to several conditions such as oral diseases. Studies have shown that propolis may restrict bacterial-plaque development and periodontitis-causing pathogens because of its antibacterial properties 53). Propolis solutions exert a selectively lower cytotoxic action on human gum fibroblasts compared to chlorhexidine. In addition to that, mouthwash containing propolis have shown effectiveness in healing surgical wounds. This encourages the use of propolis in solutions used as mouthwash 54). Propolis solution can also be used to disinfect toothbrushes 55). A 3% ethanolic extract of propolis toothpaste gel showed greater potency against gingivitis caused by dental plague in a group of patients 56). Propolis extracts have also helped cure halitosis, a condition where an individual experiences unpleasant breath predominantly due to poor oral hygiene. Propolis toothpaste or mouthwash is used for their ability to reduce growth of bacterial plaque and pathogenic microflora that causes gingivitis and periodontitis. Thus, propolis also plays a role as a therapeutic agent 57).

Cancer treatment

Propolis has potential as a complementary therapy for cancer. It has shown efficacy against various types, including bladder, blood, brain, breast, colon, head and neck, kidney, liver, pancreas, prostate, and skin cancers 58). Propolis could help prevent cancer progression; in various parts of the world it is considered an alternative therapy for cancer treatment 59). Propolis extracts have been found to inhibit tumor cell growth both in vitro and in vivo, including inhibition of angiogenesis, demonstrating potential for the development of new anticancer drugs 60). Various components of propolis have been shown to inhibit cancer cell growth, including cinnamic acid 61), caffeic acid phenethyl ester (CAPE) 62), quercetin 63) and chrysin 64). Propolis and its components normally have little impact on normal cells, displaying differential cytotoxicity in liver cancer, melanoma and breast cell carcinoma cell lines 65). Propolis enhances the activity of tumor necrosis factor related apoptosis inducing ligand in cancer cells 66).

A study reported that propolis has potential towards human breast cancer treatment due to its antitumor activity by inducing apoptosis on human breast cancer cells. It also exhibits low or no toxicity towards normal cells due to its selectively toxic properties against tumor cells and is believed that propolis may become a prominent agent to treat breast cancer 67). Another study investigating the effect of ethanolic extract of Algerian propolis on melanoma tumor growth has shown that galangin, a common flavonoid in propolis remarkably induced apoptosis and inhibited melanoma cells in vitro 68). Turkish propolis has also been shown to exert a selective cytotoxic action on human lung cancer cells by inducing endoplasmic reticulum stress, apoptosis, and caspase activity and by reducing the mitochondrial membrane potential. This indicates that propolis is able to minimize the cancer cell growth 69).

Skincare

Propolis is widely used in dermatological products such as creams and ointments. Its use in skin care products is based on its antiallergy, anti-inflammation, antimicrobial properties, and promotive action on collagen synthesis. A recent study comparing the effect of propolis and the conventional drug silver sulfadiazine showed that propolis notably decreased free radical activity in healing the wound beds which supported the repair process. A clinical study on acne patients using ethanolic extract propolis showed its high efficacy in the treatment of acne vulgaris 70). Propolis also shows positive collagen metabolism in the wound during the healing process by increasing the collagen content of tissues 71). A study demonstrated the use of propolis as an alternative therapy for wound healing to promote wound closure, especially under conditions such as human diabetic foot ulcer 72).

The molecular mechanisms responsible for the wound-healing activity of propolis is shown in Figure 3 below. Fibronectin is a multifunctional glycoprotein of high molecular weight, which influences the structural stability and functional properties of various organs and tissues. The fibronectin matrix and its accumulation are essential for cell migration, cell proliferation, cell differentiation, cell adhesion, apoptosis, cellular signaling, angiogenesis, collagen biosynthesis, re-epithelialization, clot formation, and platelet activity. Fibronectins are also important in the repair mechanisms for conditions such as glycoprotein intensified degradation, which leads to a defective cellular microenvironment and affliction in the structure of granulation tissues. This condition may prevent the wound from healing or inhibit the repair process. The accumulation of fibronectin in the extracellular space also modulates the secretion of other repairing components such as collagen type 1 and type 3, tenascin, laminin, and fibrillin.

Propolis has demonstrated favorable effects in the wound-healing process such as antifungal and antibacterial activities due to its components such as flavonoids, phenolic compounds, terpenes, and enzymes. It also reduces the activity of free radicals (ROS or reactive oxygen species) in the wound bed favoring the repair process. Propolis has also demonstrated great effects on collagen metabolism by increasing the amount of both type 1 and type 3 collagens in tissues. The reduction of ROS and accumulation of collagen aid in balancing the extracellular matrix and generating granulation tissues. Propolis is a potential apitherapeutic agent that is able to modify the metabolism of fibronectin by developing a fibrous network of extracellular matrix and inhibiting fibronectin disintegration. The active components in propolis such as quercetin and resveratrol inhibited fibronectin biosynthesis and TGF𝛽-dependent production of fibronectin, respectively, in C2C12 myoblasts. Both the components play important roles in regulating the expression of fibronectins. Studies have also shown that mobility and migration of epithelial cells are dependent on reduced fibronectin content in the extracellular matrix. Reduced amounts of this glycoprotein in propolis effectively treated wounds and produced granulation tissues. Therefore, the influence of propolis on fibronectin metabolism may alter the mechanism of wound healing 73).

Figure 3. Molecular mechanism targeting wound-healing activity of propolis

Molecular mechanism targeting wound-healing activity of propolis
[Source 74) ]

Antifungal action

Antifungals are used for the treatment and prevention of fungal infections. Commonly, these antifungal drugs are prescribed for the fungal infection of skin, hair, nail and oral candidiasis. Furthermore, they are used as a supportive therapy for patients suffering from denture stomatitis and added to denture tissue conditioners 75). Propolis extract shows excellent performance regarding in vitro tests against yeasts identified as onychomycosis agents. In low concentrations, propolis extract was not only found to be fungistatic but also fungicidal. Candida tropicalis was found to be the most resilient whereas the Trichosporon species were the most vulnerable yeasts. The results reinforce the importance and the potential of propolis extract as a treatment for fungal infection of the nail (onychomycosis) 76). The results of the study showed that all the yeasts tested were inhibited by low concentrations of propolis extract, including an isolate resistant to nystatin 77). Similarly, Ota et al 78) studied antifungal activity of propolis extract on 80 different strains of Candida yeast and found the yeasts showed a clear antifungal activity with the following order of sensitivity: Candida albicans > Candida tropicalis > Candida krusei > Candida guilliermondii. Recently, Siquera et al 79) assessed the fungistatic and fungicidal activity of propolis against different species of Candida using fluconazole as control. It was noted that propolis has fungistatic and fungicidal properties better than fluconazole.

Antiviral substance

Propolis has been tested against various viral disease organisms 80); initial successes have prompted research to determine the most useful components, which may be modified to produce more active and specific pharmaceuticals 81). Viruses that were controlled by propolis in animal models with suggestion for control in humans include influenza 82), herpes simplex virus type 2 (HSV-2) 83) and HIV 84). Shimizu et al. 85) evaluated three different types of propolis in ethanol extracts, using a mice model of herpes simplex virus-1 (HSV-1). Despite the chemical differences due to the different plant origins of the resins the bees used to produce the propolis (Baccharis dracunculifolia, Baccharis eriodata and Myrceugenia euosma), all three propolis extracts not only had direct anti-HSV-1 effects, but also stimulated immunological activity against intradermal HSV-1 infection in mice.

Antiviral activity of propolis has been reported for DNA and RNA viruses (poliovirus, herpes simplex virus, and adenovirus) in an in vitro model (cultured cells). The best results were obtained against poliovirus and herpes virus, with 99.9% inhibition of the latter, at a propolis concentration of 30 ug/ml 86). The propolis components chrysine and kaempferol caused a concentration-dependent reduction of intracellular replication of herpes-virus strains when host cell monolayers were infected and subsequently cultured in a drug-containing medium. Quercetin, another propolis component, had the same effect, but only at the highest concentrations tested (60 ug/mL) against various human herpes simplex virus strains, with a intracellular replication reduction of approximately 65%, while it reduced the infectivity of bovine herpes virus, human adenovirus, human coronavirus, and bovine coronavirus about 50%. The reduction was 70% in the case of rotavirus 87).

Anti-inflammatory and immunomodulatory properties

There is considerable evidence that propolis can reduce and alleviate the symptoms of inflammatory diseases 88) and has immunomodulatory properties 89). However, these properties can vary according to the plant origin of the propolis, as well as the extraction process/solvent used and the inflammatory protocol (cell culture, animal models, induction by lipopolysaccharides) when the propolis extracts are tested 90). Tests with animal models have shown that propolis can reduce the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), which are key pro-inflammatory mediators, and increase the levels of the regulatory cytokine IL-10 91). Kaempferol, a propolis component, reduces IL-6, TNF-alpha, and VEGF (vascular endothelial growth factor) via the ERK-NFkB-cMyc-p21 pathway 92).

Tests on macrophage cell cultures also demonstrated that propolis inhibits the production of IL-1 beta, an important component of the inflammasome inflammatory pathway, in diseases such as rheumatoid arthritis, lupus and other autoimmune diseases 93). Although the mechanisms of action are not well elucidated, these propolis components have potential as complementary supplements in the preventive treatment of chronic inflammatory diseases 94).

Hypertension and cardiovascular disease

Propolis has demonstrated anti-hypertensive effects in rat models 95). In Cameroon, it is used in popular medicine to treat various ailments, including high blood pressure 96). Propolis has been widely used as a dietary supplement for its health benefits, including cardiovascular protective effects 97). In a human trial, consumption of propolis improved critical blood parameters, including HDL (high density lipoprotein or “good cholesterol”), glutathione (GSH) and thiobarbituric acid reactive substance (TBARS) levels, demonstrating that it could contribute to a reduced risk for cardiovascular disease 98).

Propolis reduced inflammation and prevented hyperlipidemia and metabolic syndromes in highly caloric diet induced obesity in mice. Body weight gain, visceral adipose tissue, liver and serum triglycerides, cholesterol, and non-esterified fatty acids were all reduced in the propolis fed mice 99). Caffeic acid phenethyl ester, a propolis component, is a natural anti-obesity agent 100).

Thrombosis and microthrombosis

Various types of evidence demonstrate that propolis can reduce platelet aggregation and other thrombosis-related parameters. Propolis decreased thrombotic tendencies in mice by suppressing lipopolysaccharide-induced increases in PAI-1 levels 101). Propolis downregulated platelet-derived growth factor and platelet endothelial cell adhesion molecules in low-density lipoprotein knockout mice 102). Platelet aggregation was reduced by propolis in tests on human blood in vitro 103) and in other in test tube tests 104). Caffeic acid phenethyl ester (CAPE), a well-studied bioactive propolis component, inhibits collagen induced platelet activation 105).

Aging

Propolis has antioxidant properties, which could help retard or reduce aging processes 106). Caffeic acid phenethyl ester (CAPE), a propolis component, increased the lifespan of Caenorhabditis elegans, a common model organism for aging studies 107). Propolis consumption protected against cognitive decline in elderly subjects (humans) exposed to high altitudes 108). Serum TGF-β1 and IL-10 levels were significantly higher in propolis-treated elderly subjects, helping reduce inflammation, which could be the mechanism of protection against cognitive decline. Activity of superoxide dismutase (SOD), a key antioxidant in men treated with propolis was increased, while malondialdehyde, a marker of oxidative stress, decreased 109). The same tendencies were detected in a diabetic rat model 110). A randomized double-blind placebo controlled clinical study of 32 patients with chronic kidney disease (CKD), demonstrated safety of the Standardized Propolis Extract (EPP-AF®) at an oral dose of 500 mg/day after administration during 12 months, with significant reduction in proteinuria and urinary MCP1 in the propolis group compared to the placebo 111), with no side effects. Propolis has the potential to reduce neurodegenerative damage through antioxidant activity, which helps protect against cognitive impairment in Alzheimer’s disease as well as aging 112). In a mouse model of Alzheimer’s disease, coniferaldehyde, an active ingredient in propolis, had neuroprotective effects. It reduced brain beta-amyloid deposits and pathological changes in the brain, helping preserve learning and memory capacity 113).

Diabetes

Propolis was found to reduce blood glucose, blood lipids and free radicals in diabetic rats 114). It also reduced blood glucose115) and insulin resistance in diabetic rats 116). Experimental diabetic nephropathy was also prevented 117). Diabetes symptoms were reduced in a diabetic mouse model, apparently by attenuating immune activation in adipose tissues 118).

Clinical trials with diabetic patients demonstrated that propolis consumption improved antioxidant parameters 119), glycemic control 120) and the lipid profile and renal function 121). Propolis is also an antimicrobial agent with wound healing properties 122), which has proven especially useful for diabetic patients 123), who tend to develop difficult to heal wounds.

Caffeic acid phenethyl ester (CAPE) is considered an anti-obesity agent with beneficial effects on inflammation and diabetes 124). CAPE reduced insulin resistance in diabetic mice and in hepatic cell culture 125). Chrysin, another component of propolis, also has antidiabetic properties 126).

Propolis dose

Clinical trials with propolis have been conducted in various regions of the world, most of them with the limitation of a lack of standardization. Berretta et al. 127) evaluated many of them; the most common dosage used was 500 mg/day for adults. Considering the case of Standardized Propolis Extract (EPP-AF®), the clinical data until now support dosages of 375 – 500 mg of propolis/day; however, non-clinical trials indicate that much higher dosages can be tolerated and may be useful 128). The dose of 500 mg/day would be equivalent to 30 drops of propolis extract (with 11% w/v of dry matter), 3 to 4 times a day, diluted in about 100 ml of water, or 3 to 4 units/day of capsules or tablets with the equivalent amount of extract. For preventive purposes, 30 drops/day or one capsule, are usually taken.

The following propolis doses have been studied in scientific research:

  • Propolis by mouth:
    • For diabetes: 500 mg of propolis three times per day for 8 weeks. 900 mg of propolis daily for 12 weeks. 400 mg of propolis daily for 6 months.
    • For swelling (inflammation) and sores inside the mouth (oral mucositis): 80 mg of propolis (Natur Farma S.A.S.) 2-3 times daily has been used along with rinsing with bicarbonate solution.
  • Propolis applied to the skin:
    • For cold sores (herpes labialis): Creams or ointments containing propolis 0.5% or 3% applied to the lips 5 times per day at the start of cold sore symptoms.
  • Propolis as a mouth rinse:
    • For swelling (inflammation) and sores inside the mouth (oral mucositis): 5 mL of propolis 30% mouth rinse (Soren Tektoos) for 60 seconds three times daily for 7 days has been used. 10 mL of a mouth wash has been used as a gargle 3 times daily in addition to chlorhexidine mouthwash and fluconazole for 14 days. Propolis 2% to 3% (extract Standardized Propolis Extract [EPP-AF®]) has been applied to dentures 3-4 times daily for 7-14 daily.

Propolis side effects

Propolis is considered to be relatively nontoxic 129). When taken by mouth – propolis is POSSIBLY SAFE when taken by mouth appropriately. A clinical safety study was carried out at the Ribeirão Preto School of Medicine of the University of São Paulo with healthy volunteers in order to assess the safety of ingesting 375 mg/day of Standardized Propolis Extract (EPP-AF®), for five days. No adverse events were observed. The study pointed to the absence of acute toxicity after the oral use of Standardized Propolis Extract (EPP-AF®) at a dose of 375 mg daily for five days. The significant positive variation observed in the parameter HDL cholesterol needs further studies with a larger number of patients to confirm this beneficial effect on the cardiovascular system (unpublished data).

  • Asthma: Some experts believe certain chemicals in propolis may make asthma worse. Avoid using propolis if you have asthma.
  • Bleeding conditions: A certain chemical in propolis might slow blood clotting. Taking propolis might increase the risk of bleeding in people with bleeding disorders.
  • Allergies: Do not use propolis if you are allergic to bee by-products including honey, conifers, poplars, Peru balsam, and salicylates.
  • Surgery: A certain chemical in propolis might slow blood clotting. Taking propolis might increase the risk of bleeding during and after surgery. Stop taking propolis 2 weeks before surgery.

The most common and reported side effect of propolis is allergy to the resinous wax material. Propolis can cause allergic reactions, especially in people who are allergic to bees or bee products. Lozenges containing propolis can cause irritation and mouth ulcers. When applied to the skin propolis is POSSIBLY SAFE when applied to the skin appropriately. It can cause allergic reactions, especially in people who are allergic to bees or bee products. Sensitization to propolis, long recognized by apiary workers, has also been reported. Thirty-seven German beekeepers out of 1051 were allergic to propolis and showed symptoms of skin rashes after working in bee farms professionally 130). A case of eczematous dermatitis on the face after application of honey for cosmetic purposes has also been reported 131). Sensitization to propolis with cross-sensitivity to balsam of Peru, a common additive in flavoring agents, has been reported 132). Similarly, Brailo et al 133) reported a subjective case of a 20-year-old women who experienced irregular erosions covered by pseudomembranes involving the lips and oral mucosa. She used propolis-based ointments for treatment of aphthous ulcers. Moreover, Zirwas and Otto 134) claimed that with time allergic cases of propolis have increased from 0.4% to 1.4%. Adverse reactions are more common at doses greater than 15 g/day 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 135), 136).

Information regarding safety and efficacy in pregnancy and lactation is lacking 137). Furthermore, due to certain impurities in propolis, there is limited literature to recommend it in pregnant women 138). Stay on the safe side and avoid use during pregnancy. Propolis is POSSIBLY SAFE when taken by mouth while breastfeeding. Doses of 300 mg daily for up to 10 months have been used safely. Stay on the safe side and avoid higher doses when breast-feeding.

Propolis preparation may contain high levels of alcohol and may result in nausea when taken as an adjunct to metronidazole 139). Contents in propolis may interact with antiviral, anticancer, antibiotic and anti-inflammatory drugs and may manifest allergic reactions which may range from eczema, cheilitis, oral pain, labial edema and peeling of lips 140). Additionally, more research should be carried out to define the parameters of the use of propolis both in the dental and medicinal fields‏.

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 141).

Propolis interactions with medications

Be cautious with this combination.

  • Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates)

Some medications are changed and broken down by the liver. Propolis might decrease how quickly the liver breaks down some medications. Taking propolis along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking propolis, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications that are changed by the liver include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.

  • Medications changed by the liver (Cytochrome P450 2C19 (CYP2C19) substrates)

Some medications are changed and broken down by the liver. Propolis might decrease how quickly the liver breaks down some medications. Taking propolis along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking propolis, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications that are changed by the liver include proton pump inhibitors including omeprazole (Prilosec), lansoprazole (Prevacid), and pantoprazole (Protonix); diazepam (Valium); carisoprodol (Soma); nelfinavir (Viracept); and others.

  • Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates)

Some medications are changed and broken down by the liver. Propolis might decrease how quickly the liver breaks down some medications. Taking propolis along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking propolis, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications that are changed by the liver include nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Cataflam, Voltaren), ibuprofen (Motrin), meloxicam (Mobic), and piroxicam (Feldene); celecoxib (Celebrex); amitriptyline (Elavil); warfarin (Coumadin); glipizide (Glucotrol); losartan (Cozaar); and others.

  • Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates)

Some medications are changed and broken down by the liver. Propolis might decrease how quickly the liver breaks down some medications. Taking propolis along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking propolis, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications that are changed by the liver include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.

  • Medications changed by the liver (Cytochrome P450 2E1 (CYP2E1) substrates)

Some medications are changed and broken down by the liver. Propolis might decrease how quickly the liver breaks down some medications. Taking propolis along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking propolis, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications that are changed by the liver include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and drugs used for anesthesia during surgery such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), and methoxyflurane (Penthrane).

  • Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates)

Some medications are changed and broken down by the liver. Propolis might decrease how quickly the liver breaks down some medications. Taking propolis along with some medications that are changed by the liver can increase the effects and side effects of your medication. Before taking propolis, talk to your healthcare provider if you take any medications that are changed by the liver.

Some medications that are changed by the liver include lovastatin (Mevacor), clarithromycin (Biaxin), cyclosporine (Neoral, Sandimmune), diltiazem (Cardizem), estrogens, indinavir (Crixivan), triazolam (Halcion), and others.

  • Herbs and supplements that might slow blood clotting

Propolis might increase the amount of time it takes for blood to clot. Taking it along with other herbs and supplements that slow blood clotting can slow blood clotting even more and could increase the risk of bleeding and bruising in some people. Some of these herbs include angelica, clove, danshen, garlic, ginger, ginkgo, Panax ginseng, and others.

  • Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)

Propolis might slow blood clotting and increase bleeding time. Taking propolis along with medications that also slow clotting might increase the chances of bruising and bleeding.

Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

  • Warfarin (Coumadin)

Warfarin (Coumadin) is used to slow blood clotting. Propolis might decrease the effectiveness of warfarin (Coumadin). Decreasing the effectiveness of warfarin (Coumadin) might increase the risk of clotting. Use caution in you take warfarin (Coumadin) and are starting propolis.

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