Propolis is a honey bee product known for centuries for its biological and pharmacological properties. It has been extensively used due to its antibacterial, antiseptic, anti-inflammatory, and anesthetic activities. Propolis has become the subject of numerous studies developed and carried out all over the world in order to analyze its chemical composition as well as medicinal properties.
Propolis is a resinous yellow-brown to dark brown, sometimes green substance collected by worker honey bees from the growing parts of trees and shrubs (e.g., leaf buds, trunk wounds). The bees pack the propolis on their hind legs, and carry it back to their colony, where it is combined with beeswax and used by worker "hive" bees as a sealant and sterilant in the colony nest. These workers take the resinous material and add salivary secretions and wax flakes to it, then use the new product for numerous protective purposes as bee propolis. The bees use it to coat the inside of the hive, including the passageway and the brood chambers. Propolis changes consistency with temperature. At temperatures below 150C it is hard and brittle but becomes more pliable and stickier at higher temperatures (25-450C).
Propolis protects the hive in two ways: (1) it structurally reinforces the hive itself; (2) it protects the hive from microbial infection or predator infestation. Propolis has been shown to kill Bacillus larvae, the most important bacterial disease of bees.1
History of Propolis Usage
The history of bees and their products can be traced back to c. 13,000 BC. A certain amount of knowledge is attested by depictions of the bee and of hive beekeeping found during excavations. Rock paintings also provide some of the earliest evidence of gathering honey from wild colonies. At some point humans began to domesticate wild bees in hives made from hollow logs, wooden containers, pottery vessels, and woven straw baskets. Honey bees have used propolis for millions of years, and humans have used it for thousands.2 Both species find it immensely useful and beneficial. Much of the bees' success in surviving through the ages may be credited to propolis. We may yet discover we have only just scratched the surface of the benefits of this resinous wonder.
The Greek physician, Hippocrates, prescribed the use of propolis to help heal internal and external sores and ulcers. 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, to name a few.3
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, particularly because of its antimicrobial properties.4
The ancient Greeks, Romans, and Egyptians were aware of the healing properties of propolis and made extensive use of it as a medicine. Ancient Greek texts refer to the substance as a "cure for bruises and suppurating sores", and in Rome physicians used propolis in the making of poultices. The Hebrew word for propolis is “tzori”, and the therapeutic properties of tzori are mentioned throughout the Old Testament. The biblical Balm of Gilead (tzori Gilead in Hebrew) is nearly indistinguishable from propolis.
Ancient Egyptians depicted propolis-making bees on vases and other ornaments and used it to alleviate many ailments. The Egyptians had learnt from the bees, which use propolis as an “embalming” substance: the bees cover the carcass of a killed invader, which cannot be transported out of the hive, with propolis and wax. In this way, the bees restrain spread of infection caused by the decomposing carcass.
In the years 1967–1973, a series of studies were performed in Denmark, which proved the effectiveness of propolis in treatment - as well as the fact that it produces almost no side effects. Dr. Karl Lund Aagaard, a Danish biologist, was dubbed “Dr. Propolis” for his 20+ years of propolis collecting and research. After observing the effects of propolis on more than 50,000 patients in Scandinavia, Dr Aagaard drew the following conclusions:
The field of influence of Propolis is extremely broad. It includes cancer, infection of the urinary tract, swelling of the throat, gout, open wounds, sinus congestion, colds, influenza, bronchitis, gastritis, diseases of the ears, periodontal disease, intestinal infections, ulcers, eczema eruptions, pneumonia, arthritis, lung disease, stomach virus, headaches, Parkinson’s disease, bile infections, sclerosis, circulation deficiencies, warts, conjunctivitis and hoarseness.5
Records from 12th-century Europe describe medical preparations using propolis for the treatment of mouth and throat infections, as well as dental caries.
Collection and Commercial Usage
Propolis is collected by commercial beekeepers, either by scraping the substance from wooden hive parts, or by using specially constructed collection mats. The raw product undergoes secondary processing to remove beeswax and other impurities before being used in a variety of natural health care products (e.g., lozenges, tinctures, ointments, drinks). One of the non-medicinal uses of propolis is as a varnish, and it has been suggested that the special properties of Stradivarius violins may be partly due to the type of propolis used, although the claim cannot be substantiated.
Chemical Properties and Composition of Propolis
The composition of propolis can vary according to the geographic locations from where the bees obtained the ingredients. Propolis is made up of phenolic compounds, beeswax, lipids and wax, flavonoids, terpenes (e.g. B-eudesmol), bio-elements (e.g. manganese, zinc, and copper), and other substances. One of these “other substances” 3-›4-hydroxy-3,5-bis(3-methyl-2-butenyl)phenyl-2-propenoic acid, or "Artepillin C", has been found to show antiseptic activity, antioxidant activity, and strong anti-tumor activity.6, 7, 8, 9, 10, 11, 12
At least 180 different compounds have been identified so far in propolis. This table provides the major chemicals found in propolis:
The most important pharmacologically-active constituents in propolis are the flavones, flavonols, and flavanones (collectively called flavonoids), and various phenolics and aromatics. 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). Many flavonoids found in plants are glycosides.
Flavonoids are thought to account for much of the biological activity in propolis13, although other phenolic compounds are also involved. At least 38 flavonoids have been found in propolis, including galangin, kaempferol, quercetin, pinocembrin, pinostrobin and pinobanksin.14 Some of the other phenolics include cinnamic alcohol, cinnamic acid, vanillin, benzyl alcohol, benzoic acid, and caffeic and ferulic acid.
The chemical composition of propolis is highly variable because of the broad range of plants visited by honey bees when collecting the substance. Honey bees have been reported to collect propolis from numerous tree species such as poplars, alders and birches, chestnut, ash, various prunus and willows. Variations in the beeswax content of raw propolis also affect the chemical composition.
Studies indicate that the plant resins collected by bees are at least partially altered by bees prior to use in the hive. Propolis has some nutritive value, apart from the presence of small amounts of proteins, amino acids, minerals and sugars. Vitamins include small amounts of vitamins A, B1, B2, B6, C and E.15
Medicinal Properties and Usage of Propolis
Propolis is truly a fascinating compound that has a wide range of therapeutic applications. Propolis exhibits many biological properties, including immunomodulatory, anti‐inflammatory, antioxidant, antibacterial, antiviral, antifungal and antiparasitic activities, among others. Studies have been carried out using propolis from different geographic regions. Although interesting, this makes the standardization of biological assays difficult, since different propolis samples may have different chemical compositions and so do not allow comparison between results. As reported elsewhere,16 a universal standardization would be impossible and propolis' biological action should be linked to its chemical composition and plant sources.
The following are specific therapeutic effects:
Because of its strong antimicrobial activity, propolis is often known as a “natural antibiotic”. Many studies have shown an inhibitory effect on a variety of micro-organisms – antibacterial, antiviral and antifungal. Active components of propolis showing an antibacterial effect include pinocembrin, galangin, caffeic acid and ferulic acid. Propolis has been found to inhibit the synthesis of protein by bacteria, which may account for at least some of its antimicrobial effects. Antiviral components include caffeic acid, lutseolin and quercetin. Antifungal components include pinocembrin, pinobanksin, caffeic acid, benzyl ester, sakuranetin and pterostilbene. Keep in mind that the bees mix saliva or “bee lymph derived secretions” with plant resins in making propolis.17
Anticancer - Antitumor Effects
Propolis has been shown to possess anticancer properties. Two main immune-potent chemicals have been identified as caffeic acid phenethyl ester (CAPE) and artepillin C. Propolis, CAPE, and artepillin C have been shown to exert summative immunosuppressive function on T lymphocyte subsets but paradoxically activate macrophage function.18 On the other hand, they also have potential antitumor properties by different postulated mechanisms such as suppressing cancer cell 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. These findings indicate that artepillin C activates the immune system and possesses direct antitumor activity.
The good bioavailability by the oral route and good historical safety profile makes propolis an ideal adjuvant agent for future immunomodulatory or anticancer regimens.19, 20, 21
Wound Healing and Tissue Repair Effects
Propolis has been shown to stimulate various enzyme systems, cell metabolism, circulation and collagen formation, as well as improve the healing of burn wounds.22, 23 These effects have been shown to be, in part, the result of the presence of arginine in propolis.24 Propolis was found to be superior to standard wound treatment products in trials on rats.25 Propolis tissue regeneration properties, including healing, are possibly due to its antioxidant activity.26 Whenever free radicals are produced, they hamper or even block cell regeneration. Removal of free radicals by propolis flavonoids would allow regeneration of an ill organ or tissue in an ordinary way.
Propolis has been shown to inhibit the development of externally-induced stomach ulcers in rats.27 Several studies have shown propolis to be effective in treating the giardia parasite.28, 29, 30 Propolis has also been shown to improve ulcerative colitis in animal models.31, 32, 33, 34, 35
Skin Infection Effects
The flavonoids and caffeic acid derivatives of propolis have been shown to be effective in inhibiting the growth of yeasts and fungi responsible for such skin infections as ringworm and athlete's foot.36
Studies on mice have shown that extracts of propolis have an anti-inflammatory effect due to the flavonoids, artepillin C and caffeic acid compounds.37, 38, 39 These results suggest that propolis potentially has a strong anti-inflammatory activity.
Propolis and some of its components produce analgesia, which in some studies has been shown to be 3 times as powerful as cocaine and 52 times that of procaine, when tested in rabbit cornea.40 The analgesic effect has been shown in part to be produced by pinocembrin, pinostrobin, caffeic acid esters components in propolis.41, 42, 43
The analgesic effect may explain why propolis has been used for centuries in the treatment of sore throats and mouth sores. An analgesic ointment for dentistry using propolis was patented in Europe in 1983.44
Effects on Immune System
Propolis has been shown to stimulate an immune response in aged mice.45 In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity.46, 47, 48 Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production have also been demonstrated.49
Propolis has been shown to stimulate antibody formation in immunized mice. In a joint US-Polish study, spleen cells producing antibodies in mice administered a propolis extract were three times greater than controls. A second dose administered 24 hours later produced an even larger effect, although further doses reduced the effect.50
Propolis has been shown to suppress HIV-1 replication and modulate in vitro immune responses, and, according to the authors, “May constitute a non-toxic natural product with both anti-HIV-1, and immunoregulatory effects.”51
In animal studies it has been shown that propolis can reduce blood pressure, produce a sedative effect, and maintain serum glucose.52, 53, 54, 55, 56
Propolis exhibits protective effects against hepatocyte injury owing to its cytoprotective, antioxidant and anti-inflammatory effects. Propolis has also been shown to protect the liver against numerous toxic chemicals including alcohol (ethanol) and tetrachloride in rats.57, 58, 59, 60 Furthermore, it was found to protect against oxidative-liver injury in animals exposed to cold stress or cigarette smoke.61, 62
Propolis has been shown not to be toxic to humans or mammals unless very large quantities are administered.63, 64 Contact dermatitis is a well-documented allergic reaction to propolis.65, 66 Initial reports were made by beekeepers, who came into daily contact with the raw product.67, 68 Allergic reactions are now also reported in the general population, due to the more widespread use of products containing propolis. 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.
Very few other adverse reactions to propolis have been documented in the literature, and the product is considered generally not to be harmful. Rare cases of oral inflammation and ulceration, mouth edema (swelling) and stomatitis have been reported, however, as a result of oral ingestion of propolis.69, 70
Commercial Usage of Propolis
Raw propolis is col