Propolis is generally known as the “bee glue”, which is a generic name that refers to the resinous substance accumulated by the bees from different types of plants. The word “propolis” is derived from Greek to mean defense for “pro” and city or community for “polis”, or the beehive.1 The honeybees pack the propolis on their hind legs, and carry it back to their colony, where it is combined with beeswax and used as a sealant and sterilant in the colony nest. The bees then use it to coat the inside of the hive, including the passageway and the brood chambers. Thus, propolis functions in sealing holes and cracks and for the reconstruction of the beehive. It 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. Furthermore, propolis hardens the cell wall and contributes to an aseptic internal environment. Propolis generally becomes soft and sticky upon heating or changes consistency with temperature. Propolis has strong antimicrobial properties and has been shown to kill Bacillus larvae, the most important bacterial disease of bees.2 In other words, propolis protects the hive in two ways: first, it reinforces the hive itself; second, it protects the hive from bacterial and viral infection. It is this latter property that medicinally for humans has been found to be helpful through the centuries.
Propolis is collected by honeybees from tree buds or other botanical sources in the North Temperate Zone, which extends from the Tropic of Cancer to the Arctic Circle. The best sources of propolis are species of poplar, willow, birch, elm, alder, beech, conifer, and horse-chestnut trees.3 Its color varies from green to brown and reddish, depending on its botanical source.
Propolis is highly regarded for its medicinal properties for humans, especially in Eastern Europe, South America, and Asia. Propolis has numerous applications in treating various diseases due to its antiseptic, anti-inflammatory, antioxidant, antibacterial, antimycotic, antifungal, antiulcer, anticancer, and immunomodulatory properties.4, 5, 6
History of Usage
Bees have used propolis for millions of years, and humans have used it for thousands. Both species find it immensely useful and beneficial. Much of the bees' success in surviving through the ages may be credited to propolis. The Greek physician Hippocrates prescribed the use of propolis to help heal internal and external sores and ulcers. Ancient Egyptians depicted propolis-making bees on vases and other ornaments and used the resinous substance to alleviate many ailments. 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.7
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 because of its antimicrobial properties.8 Ancient Greek texts refer to the substance as a “cure for bruises and suppurating sores”, and in Rome physicians used propolis in making poultices. The honeybee was a sacred symbol of Artemis and an important design on Ephesian coins for almost 6 centuries.
The Hebrew word for propolis is “tzori”, and the therapeutic properties of tzori are mentioned throughout the Old Testament. Records from 12th century Europe describe medical preparations using propolis for the treatment of mouth and throat infections, as well as dental caries.
Beekeeping supply companies often sell traps that can be used to collect propolis. The trap consists of a thin plastic sheet that has narrow slits cut into it and replaces the inner cover on the hive. Over time, bees fill the narrow slits in the plastic when the outer cover is flat on the hive; however, leaving the outer cover propped up to allow light and air in through the top of the hive will encourage the bees to plug up the holes in the propolis trap faster.
Once the trap is plugged up with propolis it is put in a bag and placed in a freezer for at least a few hours. Immediately upon removal from the freezer the trap (still inside the bag) is banged against a hard surface such as a tabletop, or simply contorted and gently bent back and forth in order to cause the brittle propolis to crack, break and fall from the trap.
Propolis can also be collected by catching the hive scrapings when cleaning out the honey supers during the honey harvest. Unlike propolis collected from a trap, hive scrapings will tend to contain contaminants such as bits of wax, wood, dead bees, etc. One way these contaminants can be removed from the propolis is by soaking the scrapings in a pail of water. Dead bees, pieces of wood and beeswax will tend to float while the propolis will tend to sink, allowing the beekeeper to separate out most contaminants.9
Once collected, it is then turned into powder and made into capsules or a tincture. While large companies may make tablets out of propolis, small producers may purchase capsules that can be used to encapsulate the powdered propolis. Alternatively, powdered propolis can be mixed with raw honey to make an especially tasty medicine.
Chemical Properties and Composition of Propolis
The chemical composition of propolis is highly variable because of the broad range of plants visited by honeybees when collecting the substance. Variations in the beeswax content of raw propolis also affect the chemical composition. Thus, the composition of propolis is not fixed and varies considerably from region to region along with vegetation, from season to season, and from hive to hive. In each sample of propolis, more than 80 to 100 chemical compounds are typically identified.10 Altogether, at least 180 different compounds have been identified in propolis to date. A broad analysis revealed approximately 50 constituents in typical European propolis, which comes usually from trees, such as poplars and conifers. These constituents comprise primarily resins and vegetable balsams, mainly cinnamic acid and derivatives, coumaric acid, prenylated compounds, artepillin C (50%), beeswax (30%), essential oils (10%), bee pollen (5%), and minerals, polysaccharides, proteins, amino acids, amines, amides, and organic debris (5%).
The major constituents of propolis from most of the sources are flavonoids.11 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). Numerous flavonoids have been found in propolis, 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. Some of the principal phenolic esters and flavonoids like caffeic acid phenethyl ester, quercetin, baicalin, pinocembrin, naringin, galangin, and chrysin have been found to be responsible for antimicrobial, antioxidant, and anti-inflammatory activities of propolis.12, 13
Propolis has little direct nutritive value but does contain important vitamins, such as vitamins B1, B2, B6, C, and 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. Vitamins include small amounts of A, B1, B2, B6, C and E.14
Medicinal Properties and Usage of Propolis
Propolis is truly a fascinating compound that has a wide range of therapeutic applications. The following are specific therapeutic effects.
Because of its strong antimicrobial activity, propolis is often known as a “natural antibiotic”. One of the earliest investigations of the antibacterial activity of propolis was performed by Kivalkina in the 1940s. Propolis was shown to have bacteriostatic activity against Streptococcus aureus, the typhoid bacillus, and some other bacteria as well.15 Since then numerous studies have been conducted on the antimicrobial activity of propolis. A few of the early studies are summarized in the following table:
Active components of propolis showing an antibacterial effect include pinocembrin, galangin, caffeic acid and ferulic acid. Antifungal components include pinocembrin, pinobanksin, caffeic acid, benzyl ester, sakuranetin and pterostilbene. Anti-viral components include caffeic acid, lutseolin and quercetin. Propolis has been found to inhibit the synthesis of protein by bacteria, which may account for at least some of its antimicrobial effects. Keep in mind that bees mix saliva or “bee lymph derived secretions” with plant resins in making propolis. Peptides in honeybee lymph have been shown to be antimicrobial.38, 39, 40
Propolis Anticancer Effects
Probably one of the most exciting areas of propolis research is in its anti-cancerous and anti-tumorous properties. Much of is anti-cancerous effects result from its effect on the immune system. Propolis activates immune cells that produce cytokines and macrophages. Two main immunopotent chemicals in propolis have been identified as artepillin C and caffeic acid phenethyl ester (CAPE). Propolis, CAPE, and artepillin C have both been shown to activate macrophage function in destroying tumors. They also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cells 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. The good bioavailability by the oral route and good historical safety profile make propolis an ideal adjuvant agent for immunomodulatory or anticancer regimens.
Artepillin C in propolis has been shown to cause significant damage to solid tumor and leukemic cells by the MTT assay, DNA synthesis assay, and morphological observation in vitro. When xenografts of human tumor cells were transplanted into nude mice, the cytotoxic effects of artepillin C were most noticeable in carcinoma and malignant melanoma. Apoptosis, abortive mitosis, and massive necrosis combined were identified by histological observation after intratumor injection of 500 g of artepillin C three times a week. In addition to suppression of tumor growth, there was an increase in the ratio of CD4/CD8 T cells, and in the total number of helper T cells. These findings indicate that artepillin C activates the immune system, and possesses direct antitumor activity .41
The cancer inhibitory effects of caffeic acid phenethyl ester (CAPE) has been confirmed in a variety of culture cell lines. A particularly high concentration of this compound was found in the New Zealand propolis called BIO 30 and shown to suppress tumor growth.42, 43, 44
Previous studies have shown the usefulness of CAPE through its anti-inflammatory45, 46, 47, immunostimulatory and antitumor activity.48, 49, 50 CAPE exhibits strong antitumor effects in oral cancer cells, including the neck and tongue, and many proteins involved in the apoptotic process are affected by CAPE.51
Propolis Oral Health Benefits
The oral cavity has an abundant bacterial microflora and excessive bacterial growth may lead to not only oral diseases but also systemic diseases. Studies have shown that propolis may restrict bacterial-plaque development and periodontitis-causing pathogens because of its antibacterial properties.52 Propolis solutions exert a selectively lower cytotoxic action on human gum fibroblasts compared to chlorhexidine. In addition, mouthwash containing propolis has shown effectiveness in healing surgical wounds.53 Propolis solution can also be used to disinfect toothbrushes.54 Propolis toothpaste and/or mouthwash is used for its ability to reduce growth of bacterial plaque and pathogenic microflora that cause gingivitis and periodontitis.
Propolis Wound Healing and Tissue Repair Effects
It has long been known that propolis and its extracts have a positive effect on tissue regeneration. Research has shown that an application of an alcoholic solution of propolis accelerates the tissue regeneration process.55 As far back as 1977, Polish researchers showed that application of ethanol extract of propolis promotes the healing processes in damaged cartilage56 as well as enhances ossification in artificially-induced bone defects.57 It has also been demonstrated that propolis extract supports regeneration of dental pulp and reduces inflammatory and degenerative processes as well.58 Part of the healing effect is because propolis stimulates various enzyme systems affecting cell metabolism, microcirculation and collagen formation.
Gastric and duodenal ulcers affect a considerable number of people in the world and are induced by several factors, such as: stress, smoking, nutritional deficiencies and ingestion of certain drugs, such as non-steroidal-anti-inflammatories. The current medicinal treatment of peptic ulcer is generally based on the inhibition of gastric acid secretion by histamine H2 antagonists, proton-pump inhibitors and antimuscarinics. However, most of these drugs produce adverse reactions, such as hypersensitivity, arrhythmia, and hematopoietic changes. Thus, it is necessary to develop more effective and less toxic antiulcer approaches that improve the gastrointestinal microbiome and its function. Propolis has long been used for digestive problems and has been shown to inhibit the development of stomach ulcers.59, 60, 61 It appears that the flavonoid components of propolis are primarily responsible for its antiulcer effects.62 In several studies propolis has been shown to improve different types of colitis. 63, 64, 65
The modulation of cardiovascular disease markers by propolis has been shown in several studies. In vitro and in vivo assays have described the molecular mechanisms of its beneficial effect: regulation of glucose and lipoprotein metabolism; decrease of oxidative stress; improvement of endothelial function; inhibition of platelet aggregation; and reduction of blood pressure.
Propolis has been shown to modulate lipid and lipoprotein metabolism. Propolis administration has diminished liver cholesterol and triglyceride content and decreased the rate of hepatic triglyceride synthesis in rats.66, 67 Polyphenols from propolis inhibited the progression of atherosclerosis in mice by improving the lipid profile and by downregulating proinflammatory cytokines, chemokines, and angiogenic factors.68
Platelet aggregation is a major contributor to the atherosclerotic process. Propolis components have been shown to inhibit platelet aggregation. Specifically, caffeic acid phenethyl ester (CAPE) in propolis has been shown to markedly inhibited collagen-stimulated platelet aggregation. As CAPE is involved in various inhibitory pathways influencing platelet aggregation, it may be an important contributor to the potent antiplatelet actions of propolis.69 In several animal studies, a concentrated extract of propolis has been shown to reduce blood pressure.70, 71 Overall, propolis constituents have been shown to be beneficial for many causes of cardiovascular disease.
Adverse Effects of Propolis
Propolis is not known to be toxic to humans or mammals unless very large quantities are administered.73 The main adverse effect reported by beekeepers, which consume and come into daily contact with the raw product is contact dermatitis. Dermatitis can be produced by skin contact with raw propolis, as well as propolis extracts and products containing caffeic acid and its derivatives have been identified as the major allergenic agent.74, 75, 76 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. Rare cases of oral inflammation and ulceration, mouth edema (swelling) and stomatitis have been reported as a result of oral ingestion of propolis.77, 78 Very few other adverse reactions have been documented in the literature, and the product is considered generally not to be harmful.
Recorded use of propolis dates to c. 3000 BC and continues today in the form of home remedies, toothpastes, creams, ointments, tinctures, capsules and in dietary supplements. Its numerous beneficial medicinal properties have long been appreciated. There are clearly a multitude of options for future research related to propolis ranging from its chemical attri