Propolis Description

Propolis is a resinous substance collected by worker honey bees from the growing parts of trees and shrubs (eg., 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. The uses take advantage of the antibacterial and antifungal effects of propolis in protecting the colony against disease. Propolis has also been shown to kill Bacillus larvae, the most important bacterial disease of bees (Mlagan and Sulimanovic, 1982).

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 (eg., lozenges, tinctures, ointments, toothpaste).

History of Use

Propolis is derived from the Greek works pro ("before") and polis ("city"), and refers to the observation made by beekeepers in ancient times that bees often built a wall of propolis at the front entrance of their colony (ie, "before the city‘).

Propolis has been used by man since early times, for various purposes, and especially as a medicine because of its antimicrobial properties (Crane, 1997). Ancient Greek texts refer to the substance as a "cure for bruises and suppurating sore", and in Rome propolis was used by physicians in making poultices. The Hebrew word for propolis is tzori, and the therapeutic properties of tzori are mentioned throughout the Old Testament. Records from 12^th century Europe describe medical preparations using propolis for the treatment of mouth and throat infections, and dental caries (Krell, 1996).

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.

Production and Consumption

Official records on current world propolis production are not available, although it was estimated that in 1984 approximately 200 tonnes was traded on the world market (Crane, 1990.) Major producers include China, Brazil, USA, Australia and Uruguay.

Japan is a major consumer of propolis. In 1995, the total retail market for propolis products was estimated to be ¥20 million (NZ$282 million) (TRADENZ, 1995). Annual New Zealand consumption is estimated at 9.9 million daily doses.

Composition

At least 180 different compounds have been identified so far in propolis. A list of the major chemicals occurring in propolis is given in the following table (Krell, 1996):

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.

Flavonoids are thought to account for much of the biological activity in propolis (Grange and Davey, 1990). At least 38 flavonoids have been found in propolis, including galangin, kaempferol, quercetin, pinocembrin, pinostrobin and pinobanksin (Schmidt and Buchmann, 1992). Some of the phenolics include cinnamyl 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. Crane (1990) identifies at least 67 species from which honey bees have been reported to collect propolis material. Important sources include poplars, alders and birches, chestnut, ash, various Prunus and willows. Variations in the beeswax content of raw propolis also affect the chemical composition.

The plant species available in a geographic area determine the kinds and amounts of important compounds present in propolis. A recent study of New Zealand propolis found that the important dihydrofavonoids pinobanksin and pinocembrin made up approximately 70% of the flavonoids in the samples analysed (Markham, et al, 1996). A similar study of Brazilian, Uruguayan and Chinese samples showed dihydroflavonoids to comprise less than 10% in all but one sample, which had 50%.

Studies indicate that the plant resins collected by bees are at least partially altered by bees prior to use in the hive (Cuellar et al, 1990). The presence of sugars also suggest some metabolising by bees (Greenaway et al, 1987).

Human Nutrition

Propolis has little direct nutritive value, apart from the presence of small amounts of proteins, amino acids, minerals and sugars. Vitamins include small amounts of A, B₁, B₂, B₆, C and E (Ghisalberti, 1979).

Dihydroflavonoids, like those found in propolis, have been shown to aid the human body in absorbing Vitamin C (Bors, et al, 1995).

Propolis is used by humans almost solely as a therapeutic. Propolis and a number of its components exhibit a wide variety of biological and pharmacological activities (Schmidt and Buchmann, 1992).

Therapeutic Properties

Antimicrobial Effects

Because of its strong antimicrobial activity, propolis is often known as a "natural antibiotic". A large number of studies have shown an inhibitory effect on a variety of micro-organisms. The antimicrobial effects are summarised in the following table (Krell, 1996):

Active components of propolis showing an antibacterial effect include pinocembrin, galangin, caffeic acid and ferulic acid. Antifungal components include pinocembrin, pinobanksin, caffeic acid, benzy ester, sakuranetin and pterostilbene. Anti-viral components include caffeic acid, lutseolin and quercetin (Schmidt and Buchmann, 1992).

Anticancer Effects

Ethanol extracts of propolis have been found to transform human hepatic and uterine carcinoma cells in vitro, and to inhibit their growth (Matsuno, 1992). Substances isolated in propolis which produce this cytotoxic effect are quercetin, caffeic acid, and clerodane diterpendoid. Clerodane diterpendoid shows a selective toxicity to tumour cells.

Propolis was also found to have a cytotoxic and cytostatic effect in vitro against hamster ovary cancer cells and sarcoma-type tumours in mice (Ross, 1990). The substance has also displayed cytotoxicity on cultures of human and animal tumour cells, including breast carcinoma, melanoma, colon, and renal carcinoma cell lines. (Grunberger et al, 1988). The component producing these effects was identified as caffeic acid phenethy ester.

A substance called Artepillin C has been isolated from propolis, and has been shown to have a cytotoxic effect on human gastric carcinoma cells, human lung cancer cells and mouse colon carcinoma cells in vitro (Kimoto, et al, 1995).

Antioxidant Effects

The flavonoids concentrated in propolis are powerful antioxidants, and have been shown to be capable of scavenging free radicals and thereby protecting lipids and other compounds such as Vitamin C from being oxidised or destroyed (Popeskovic, et al, 1980). It is probable that active free radicals, together with other factors, are responsible for cellular ageing and degradation in such conditions as cardiovascular diseases, arthritis, cancer, diabetes, Parkinson disease and Alzheimer disease.

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 (Ghisalberti, 1979; Krell, 1996). These effects have been shown to be the result of the presence of arginine in propolis (Gabrys, et al, 1986). Propolis and aloe vera was found to be superior to standard wound treatment products in trials on mice (Sumano-Lopez, et al, 1989).

Anaesthetic Effects

Propolis and some of its components produce anaesthesia, 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 (Ghisalberti, 1979). The anaesthetic effect has been shown to be produced by pinocembrin, pinostrobin, caffeic acid esters components in propolis (Paintz and Metzner, 1979).

The anaesthetic effect may explain why propolis has been used for centuries in the treatment of sore throats and mouth sores. An anaesthetising ointment for dentistry using propolis has been patented in Europe (Sosnowski, 1984).

Effects on Immune System

Propolis has been shown to stimulate an immune response in mice (Manolova, et al, 1987). More recently, Japanese researchers have shown an extract of propolis to produce a macrophage activation phenomenon related to the immune function in humans (Moriyasu, et al, 1993). Propolis activates immune cells which produce cytokines. The results help to explain the anti-tumour effect produced by propolis.

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" (Harish, et al, 1997).

Cardiovascular Effects

In mice, a concentrated extract of propolis has been shown to reduce blood pressure, produce a sedative effect, and maintain serum glucose (Kedzia et al, 1988). Dihydroflavonoids, as contained in propolis, have been shown to strengthen capillaries (Roger, 1988), and produce antihyperlipidemic activity (Choi, 1991). Propolis has also been shown to protect the liver against alcohol (ethanol) and tetrachloride in rats (Coprean, et al, 1986).

Dental Care Effects

In rats inoculated with S. sobrinus, about half of their fissures were carious, while dental caries were significantly less in rats given water containing propolis extract. No toxic effects of propolis on the growth of rats were observed under experimental conditions in this study (Ikeno, et al, 1991). Propolis has also been shown to be effective as a subsidiary treatment for gingivitis (gum infections) and plaque (Neumann, et al, 1986). A 50% propolis extract was found to antiseptic against pulp gangrene (Gafar, et al, 1986).

Clinical Effects on Humans

A total of 260 steel workers suffering from bronchitis were treated for 24 days by various methods including local and systemic regulation of the immune system and local treatment with an ethanol extract of propolis (EEP) in a physiological salt solution. Best results were obtained with inhalation of the extract, together with propolis tablets (Scheller et al, 1989a). Propolis has also shown positive effects in other otorhinolaryngologic diseases, such as pharyngitis (Doroshenko, 1975), chronic bronchitis (Scheller, et al, 1989a), rhinopharyngolaryngitis (Isakbaev, 1986), pharyngolaryngitis (Lin, et al, 1993), catarrh (Zommer-Urbanska et al, 1987), and rhinitis (Nunex, et al, 1988).

Sixty students were divided into groups to test the effect of propolis on the development of plaque and gingivitis. The results suggest that a propolis preparation can be a useful subsidiary treatment in oral hygiene (Neumann, et al, 1986).

A strong immune deficiency was found in 2 patients with alveolitis fibroticans. Treatment with a combination of the propolis, Esberitox N and calcium-magnesium resulted in good improvements in the state of the immune system and the clinical condition of both patients (Scheller et al, 1989 b).

Clinical applications of propolis (1-10%) in ether or alcohol were effective against 10 superficial fungi and 9 deep-growing fungi. On oral treatment of 160 psoriasis patients with 0.3 g propolis 3 times daily for 3 months, about one-third were cured or greatly improved (Fang Chu, 1978).

Patients (110) infected with ringworm were treated with 50% propolis as a unguent. In 97 patients it was found to produce excellent results (Bolshakova, 1975).

Sixty-four patients with tibial skin ulcers, aged from 23 to 98 years, were treated using propolis tincture in an ointment. The ointment was applied daily to the ulcerated area, which was also treated on the periphery with antibiotic ointments. The treatment lasted for 4-12 weeks. At the end of treatment, 19 of the 64 treated patients exhibited no clinical signs of the condition, 19 an improved condition (Korsun, 1983).

Patients (229) with burns, clean wounds, infected wounds or abscesses/ulcers were treated with a cream containing propolis at two concentrations (2% and 8%). The higher concentration caused local intolerance in 18% of patients by day 9, whereas the lower concentration caused symptoms in only 1.8% of patients by day 16. Burns and wounds treated with the low concentration cream healed in 11 days on average, septic wounds in 17.5 days, 67% of ulcers in 36 days (Morales and Garbarino, 1996).

Patients (126) suffering external otitis, chronic mesotypanic otitis and tympan perforation were treating with propolis solutions (5-10%). A positive therapeutic result was reported in most cases (Matel, et al, 1973). Propolis has also shown positive results in the treatment of acute inflammations of the ear (Palos, et al, 1989).

Patients (90) with cases of vagina and uterus cervix inflammation caused by S. pyogenes were treated with 3% propolis ethanol extract. Over 50% of the cases responded well to this treatment (Zawadzki and Scheller, 1973).

Patients (138) suffering giardiasis were treated with propolis extracts (10-20%). In children, 52% showed a cure at the lower dose. In adults, the cure rate was the same as for tinidazole, an antiprotozoan drug, at the 20% extract, and 60% vrs. 40% for tindazole at a higher concentration (30% propolis extract) (Mirayes, et al, 1988).

The diverse use of propolis in clinical trials shows that its therapeutic efficacy lies mainly in diseases caused by microbial contaminations (Marcucci, 1995).

Adverse Effects

Propolis has been shown not to be toxic to humans or mammals unless very large quantities are administered (Ghisalberti, 1979). Some of its constituent flavones, eg., quercetin, might be mutagenic by the Ames test, but mutagenicityper se for propolis has not been reported (Schmidt and Buchmann, 1992).

Contact dermatitis is a well-documented allergic reaction to propolis (Hausen et al, 1987). Dermatitis can be produced by skin contact with raw propolis, as well as propolis extracts and products containing extracts, and this can cause problems for some beekeepers and other users. Caffeic acid and its derivatives have been identified as the major allergenic agent (Hashimoto, et al, 1988). 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 (Schmidt and Buchmann, 1992).

Commercial Use

Raw propolis is collected by beekeepers and sold in bulk to companies that refine the product and turn it into usable extracts. Most commercial uses of propolis are based on preparations made up from these extracts. Methods include ethanol extraction (EEP), glycol extraction (GEP), aqueous (water) extraction (AEP), oil extraction (OEP), and water-soluble derivatives (WSD). Where solvents are used, reduction or elimination of the solvent is necessary, either by freeze-drying, vacuum distillation, or evaporation. Extraction is used to remove the beeswax which is mixed with the propolis by the bees during use in the hive, as well as other non-active components such as resinous-balsam substances.

Main commercial uses of propolis are as a dietary supplement and therapeutic. Propolis is sold in tablets (singularly, or in combination with other substances such as pollen, royal jelly and non-hive products), and tinctures, and as an ingredient in lozenges, skin creams, shampoos, lipsticks, toothpastes and mouthwashes. Tinctures and lozenges are popular treatment for sore throats, and tinctures are often used to treat cuts, mouth sores and skin rashes. The antioxidant, antimicrobial and antifungal activities of propolis also offer opportunities in food technology. In Japan, the use of propolis is permitted as a preservative in frozen fish (Krell, 1996).

Propolis is a stable product, but should nevertheless be stored in airtight containers in the dark, preferably away from excessive and direct heat. Propolis does not lose much of its antibiotic activity, even when stored for 12 months or longer. Propolis and its extract function as a mild preservative due to their antioxidant and antimicrobial activities and thus may actually prolong the shelf life of some products (Krell, 1996).

Food Safety

Because of its antioxidant and antimicrobial activities, microbial contamination is not considered to be a problem with propolis, either in the raw form, or as extracts.

Concentrations of lead above maximum allowable levels for food products have been found in propolis. Studies have shown that lead levels may be reduced by placement of hives away from areas with heavy air pollution and the use of oil based paints on hive parts (Alcici, 1996). Propolis destined for commercial use should be routinely tested for lead concentration.

Quality Control

No international standards exist for propolis. Official standards exist for propolis in several East European countries. Maximum and minimum limits for certain chemicals are set, but few standardised tests are available to determine the biological activities of various components.