RESEARCH & JOURNAL ARTICLES ON PROPOLIS

1. Propolis and Dental Plaque

2. Article from the Nutrition Reporter

3. Research from Medscape
    Herbal Preparation May Prevent Respiratory Tract Infection in Children

4. Materia Medica of Propolis

5. Medical Research on Propolis

6. Propolis Research Review

Bee Propolis Fights Dental Plaque

Bee propolis helps prevent the formation of dental plaque, according to new research. This effect seems to be due to its ability to inhibit the activity of certain enzymes, which synthesize glucans from sucrose.

  • Researchers analyzed propolis extracts, from samples obtained from 2 different regions in Brazil and analyzed the activity of enzymes exposed to the extracts.
  • The propolis effectively inhibited the activity of the enzymes from 45% to 95% at concentrations between 0.75 and 3.0 mg of propolis/ml.
  • The study's authors note that propolis has been used for thousands of years in folk medicine.

They also note that the active compound in propolis responsible for this anti-plaque effect, is unknown and attempts should be made to identify it.


Caries Research September-October, 2000;34:418-426


2.  ARTICLE FROM THE NUTRITION REPORTER

Medical Journals Document Value of Bee Propolis, Honey and Royal Jelly

Copyright © 1995 by Jack Challem, The Nutrition Reporter™
All rights reserved.
When it comes to bee pollen, propolis, and royal jelly, people either seem to swear by them or swear at them.

Bee products epitomize everything that's right and wrong about natural foods and dietary supplements. For a lot of people, the concept of eating "beestuff" - other than honey - seems awfully strange. And while bee products have a faithful following, few people really understand why they work. Scientifically,that is.

Not surprisingly, physicians usually bristle at the thought of people popping bee pollen and propolis capsules. One doctor, almost 20 years ago, warned in a medical journal that patients shouldn't get "stung" by the miracle claims of bee pollen.

Even worse, advocates of bee products can often be their own worst enemies with wild cure-all claims of everything from arthritis to sexual impotence.

Bee products don't cure everything. But in a search of recent medical journal articles - most turned out to be from overseas - I found impressive documentation for propolis and honey as powerful, natural antibiotics. Amazingly, some doctors have even used honey-soaked gauze as wound dressings. And a few of the components of propolis and royal jelly even have anti-cancer properties.

As for allergies, bee pollen might help you the way it helped Sen. Tom Harkin (D-Iowa). But there's a dearth of medical journal reports on pollen, except to point out that it can cause dermatitis or anaphylactic shock.

Propolis

Bees create propolis by collecting a resinous sap from trees and then mixing it with wax back at the hive. They use this material much the way people use caulk: to seal their homes. Chemically, propolis is exceedingly complex and contains a rich variety of potent terpenes and benzoic, caffeic, cinnamic,and phenolic acids. It's also high in flavonoids, which by themselves may account for many of the benefits attributed to propolis-and some researchers refer to propolis as a type of flavonoid.

Most medical articles, however, still point to the value of propolis as a powerful, natural antibiotic. That doesn't mean eating propolis will let you throw away your antibiotics - only that you may not need them quite as often.

Why would bees need substances with broad antibacterial and antiviral properties? Any beekeeper will tell you the answer. Bees are very susceptible to bacterial and viral infections, which can destroy hives the way the bubonic plague ravaged Europe in the 17th century.
Two medical journal articles document the activity of propolis specifically against Staphylococcus aureus, the bacterium that causes dangerous and often deadly surgical infections, blood poisoning, and a type of pneumonia. Five to 10 percent of all patients hospitalized in the United States develop such infections, and S. aureus has become resistant to all but one pharmaceutical antibiotic.

In a Chinese study, researchers found that extracts of propolis - specifically, sinapic, isoferulic, and caffeic acids - inhibited the growth of S. aureus (Qiao Z, China Journal of Chinese Materi Medica, Aug. 1991;16:481-2). A European study reported that ethanol extracts from propolis had a "marked synergistic effect" on the anti-staph activity of two antibiotics, streptomycin and cloxacillin, and a moderate effect on several others (Krol W, Arzneimittel-Forschung, May 1993;43:607-9).

Another scientific investigation discovered that propolis inhibited the activity of several streptococcal bacteria species that cause dental caries.Japanese researchers reported that propolis-fed laboratory fats had far fewer caries than those given a regular diet. Propolis protected specifically against Streptococcus mutans and several other strep species (Ikeno K, Caries research, 1991;25:347-51). These strep species are closely related to the germ that causes strep throat.

Propolis works against bacteria in several ways. One study reported that it prevented bacterial cell division and also broke down bacterial walls and cytoplasm, which is how some prescription antibiotics work (Takaisi-KikuniNB, Planta Medica, June 1994;60:222-7).

Perhaps more remarkable is that propolis acts against viruses, which antibiotics do not. A number of medical journal reports have discussed the role of propolisin fighting upper respiratory infections, such as those caused by the common cold and influenza viruses (Focht J, Arzneimittel-Forschung, Aug. 1993;43:921-3). Other investigators have reported that the cinnamic acid extracts of propolis prevent viruses from reproducing, but they worked best when used during the entire infection (Serkedjieva J, Journal of Natural Products, March 1992;55:294-302).
Underpinning many of the benefits of propolis is that some of its components,like the flavonoids and ethanols, function as antioxidant free-radical scavengers. A study published in the Journal of Ethnopharmacology (Jan. 1994;21:9-13)noted that some of the antioxidant phenols in propolis functioned similarly to vitamin E. In another article, researchers described that propolis had anti-inflammatory properties and that it could also prevent blood clots(Drugs Under Experimental & Clinical Research, 1993; 19:197-203).

Honey

Six medical journal articles over the past three years have also described the antibiotic properties of honey. A physician at the medical college in Maharashtra, India, recently explored the use of honey-soaked gauze to treat burn patients. The 40 patients treated with honey healed in about half the time - and with half the scar tissue - compared with patients treated by other means. (Subrahmanyam M, Burns, Aug. 1994;20:331-3).

A team of researchers from the department of surgery, University Teaching Hospital, Nigeria, reported that unprocessed honey "inhibited most of the fungi and bacteria" causing surgical and wound infections. In a remarkable conclusion in the journal Infection (Jul.- Aug. 1992;20:227-9),Dr. S. E. Efem and his colleagues wrote, "Honey is thus an ideal topical wound dressing agent in surgical infections, burns and wound infections."

Perhaps most remarkable is the effect of honey on Helicobacter pylori, the bacterium now known to cause gastric ulcers. Because honey has long been a folk remedy for dyspepsia, or stomach upset, a team of researchers from the University of Waikato, New Zealand, tested whether honey would have any benefit. Within three days, honey stopped the growth of H. pylori colonies obtained from patients.

Royal Jelly

Highly touted royal jelly, fed to the debutante larvae that grow into queen bees, contains a powerful antibacterial protein that Japanese researchers discovered and named royalisin. Rich in amino acids, royalisin is primarily effective against "Gram-positive" bacteria, which include staph and strep species (Fujiwara S, Journal of Biological Chemistry, July 5,1990;265:11333-7).
In sum, we could learn a lesson from bees that eat honey and royal jelly, and seal their hives with propolis. By eating these bee products, we can preventively "innoculate" ourselves against many bacterial and viral infections.

So, in light of the scientific evidence, next time you hear someone ridicule bee propolis, royal jelly, and other products, just tell them to "buzz off."

This article originally appeared in the Natural Foods Merchandiser, published by New Hope Communications. The information provided by Jack Challem and The Nutrition Reporter™ newsletter is strictly educational and not intended as medical advice. For diagnosis and treatment, consult your physician.

copyright © 1996 The Nutrition Reporter™ - updated 12/04/96
for more information contact jack@thenutritionreporter.com
return to www.thenutritionreporter.com/ (The Nutrition Reporter homepage)
you are at: www.thenutritionreporter.com/bee_stuff.html

3.  RESEARCH FROM MEDSCAPE

Herbal Preparation May Prevent Respiratory Tract Infection in Children

Yael Waknine
March 2, 2004 — An herbal preparation containing echinacea, propolis, and vitamin C may be effective in preventive respiratory tract infections in children, according to results of a randomized, double-blind, placebo-controlled multicenter study published in the March issue of the Archives of Pediatric and Adolescent Medicine.

The herbal preparation (Chizukit) is made up of 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C. Echinacea is thought to have cytokine-modulating, macrophage, and natural killer cell activity, according to Herman A. Cohen, MD, and colleagues, from the Pediatric and Adolescent Ambulatory Community Clinic in Petach Tikva, Israel.

Propolis has been shown to have antimicrobial and general anti-inflammatory effects, as well as some antiviral effect on herpes simplex virus type 1 and the influenza virus. Vitamin C is thought to increase proliferative responses of T lymphocytes in vitro, and to induce production of interferon in cell culture. Because concentrations of vitamin C are up to 100 times greater in phagocytes and lymphocytes than in plasma, vitamin C may have a physiologic role in these immune system cells, according to the authors.

The investigators included 430 children aged one to five years in the study. The children were randomized to the herbal preparation (n = 215) or placebo elixir (n = 215) for 12 weeks. Both groups received twice-daily doses of 5.0 mL (age, 1-3 years), or 7.5 mL (age, 4-5 years). Both doses were given four times daily during episodes of acute illness.

Of the initial cohort, 328 children completed the study. Reasons for withdrawal included unpleasant taste, lack of confidence in the treatment, and noncompliance without explanation. Because all drop-outs occurred during the first week of the study, and differences between the groups were insignificant (P approaching 1.00 for all), an efficacy study was performed instead of an intent-to-treat analysis.

After the drop-out period, 160 children remained in the herbal-preparation group (mean age, 38.3 ± 18.6 months), and 168 children remained in the placebo group (mean age, 38.9 ± 20.6 months). Findings were similar across age groups.

The herbal-preparation group showed a significant decrease in the number of illness episodes compared with the placebo group (138 vs. 308; 55% reduction). The mean number of episodes per child was also significantly decreased (0.9 ± 1.1 vs. 1.8 ± 1.3; 50% reduction; P < .001), as was the mean number of days with fever per child (2.1 ± 2.9 days vs. 5.4 ± 4.4 days; 62% reduction; P < .001).

The total number of illness days was significantly lower in the herbal-preparation group compared with the placebo group (mean, 2.6 ± 4.2 days vs. 6.2 ± 5.0 days; P < .001), as was mean duration of individual episodes (1.6 ± 1.9 days vs. 2.9 ± 1.6 days; P < .001).

Adverse reactions were rare, mild, and transient, and they were similar between the groups (P = .54). The mild gastrointestinal and palatability symptoms did not require discontinuation of treatment.

"This decrease in upper respiratory tract infections in young children would have significant economic and social ramifications," comments Shilpa Sangvai, MD, from the Children's Hospital of Pittsburgh in Pennsylvania, in an accompanying Journal Club report. "Shortcomings of the study include lack of data comparing demographic characteristics between treatment groups, large attrition resulting in change from intention-to-treat to a per-protocol analysis, and lack of clearly defined outcomes."

"Nevertheless, we find the magnitude of the results compelling," Dr. Sangvai writes.
"Considering that this is the first trial conducted in young children, conclusions must be made with caution," Dr. Cohen and colleagues advise. "Additional studies are needed in larger samples to confirm our findings and to rule out potential adverse effects in general or specific populations at risk, such as allergic children or those receiving cotherapy or having different morbidities, before the preparation can be recommended for routine clinical use."

The study was independently funded. The authors reported no pertinent financial disclosures.
Arch Pediatr Adolesc Med. 2004;158:217-221, 222-224
Reviewed by Gary D. Vogin, MD
Yael Waknine is a freelance writer for Medscape.

4.   MATERIA MEDICA OF PROPOLIS

DESCRIPTION

Propolis, also known as bee glue and bee propolis, is a brownish resinous substance collected by bees, mainly from poplar and conifer buds, and used to seal their hives. Because of antimicrobial properties of propolis, it helps keep hives free of germs. Propolis has a long history of use in folk medicine and was even used as an official drug in London in the 1600s. Over time, propolis has been used for many purposes and marketed as lozenges, cough syrups, toothpastes, mouth rinses, lipsticks, cosmetics and even for the varnishing of Stradivarius violins. It appears to have antimicrobial and anti-inflammatory activities.

The composition of propolis is variable, depending on the locale and variety of trees and other plant species used for the collection. For example, unique constituents have been identified in propolis collected in Cuba and Brazil. The main chemical classes found in propolis are flavonoids, phenolics and terpenes. The flavonoids include quercetin, apegenin, galangin, kaempferol, luteolin, pinocembrin, pinostrobin and pinobanksin. The phenolic ester (caffeic acid phenethyl ester or CAPE) present in propolis is receiving much attention in the medical research community because of its potential for the treatment of a number of disorders, including spinal cord injury. Most of the substances in propolis are poorly soluble in water.

ACTIONS AND PHARMACOLOGY

ACTIONS

A list of possible actions of propolis includes: antibacterial, antifungal, antiviral (including anti HIV-1 activity), antioxidant, antithrombotic and immunomodula- tory.

MECHANISM OF ACTION

The mechanism of the possible actions of propolis may be understood by reviewing research findings on some of the individual compounds found in it. It is difficult to study the mechanism of actions of more than one compound at a time. Therefore, the following descriptions apply only to single compounds. The contribution of any single compound to the possible action of such a complex substance as propolis is difficult to know.

Caffeic acid phenethyl ester (CAPE) inhibits the lipoxygenase pathway of arachidonic acid, resulting in anti-inflammatory activity. CAPE is also known to have antimitogenic and immunomodulatory properties. CAPE has been found to completely inhibit the activation of the nuclear transcription factor NF-Kappa B by TNF, as well as by other pro-inflammatory agents. The inhibition of NF-Kappa B activation may provide the molecular basis for its immunomodulatory, anti-inflammatory and antiviral activities. It is possible that CAPE exerts its effects by inhibiting reactive oxygen species (ROS) production. ROS are known to play a major role in the activation of NF-Kappa B.

Compounds in propolis found to have antibacterial activity include a polyisoprenylated benzophenone, galangin, pinobanksin and pinocembrin. The exact mechanism of antimicrobial action of these compounds is not known.

INDICATIONS AND USAGE

There is evidence that propolis has some broad antimicrobial activity and that it may have anti-inflammatory effects that could make it useful in the treatment of some forms of arthritis, among other disorders.

RESEARCH SUMMARY

have shown anti-bacterial, anti-viral and anti-fungal effects. It shows activity in culture against a broad spectrum of pathogens, including influenza and herpes viruses, as well as HIV and various fungal and bacterial organisms.

In a study of school children, an aqueous propolis extract was judged effective in reducing the incidence and intensity of acute and chronic rhinopharyngitis. In another study involving 10 volunteers, it exerted activity against oral bacteria. A Cuban study concluded that propolis is more effective than tinidazole against giardia.

In vitro studies have shown propolis-related anti-inflammatory effects. Various extracts of propolis have also shown anti-inflammatory activity in animal models, particularly against adjuvant-induced arthritis.

More research is needed to further explore these preliminary findings.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

 

CONTRAINDICATIONS

Propolis is contraindicated in those who are allergic or hypersensitive to any of its components.

PRECAUTIONS

Pregnant women and nursing mothers should avoid using propolis supplements.

ADVERSE REACTIONS

There are reported adverse reactions in those using topical preparations of propolis. These reactions are manifested as dermatitis. There are reports of hypersensitivity reactions to ingested propolis, including rhinitis, conjunctivitis, skin rashes and bronchospasm.

OVERDOSAGE

No reported overdosage of propolis.

DOSAGE AND ADMINISTRATION

No typical dose. Propolis is available in several different preparations, including lozenges, tablets, creams, gels, mouth rinses, toothpastes and cough syrups.

HOW SUPPLIED

Capsules — 120 mg, 500 mg, 650 mg
Liquid
Lozenge — 50 grains
Tablets — 500 mg

LITERATURE

Burdock GA. Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol. 1998; 36:347-363.

Chopra S, Pillai KK, Husain SZ, Giri DK. Propolis protects against doxorubicin-induced myocardiopathy in rats. Exp Mol Pathol. 1995; 62:190-198.

El-Ghazaly MA, Khayyal MT. The use of aqueous propolis extract against radiation-induced damage. Drugs Exp Clin Res. 1995; 21:229-236.

Grange JM, Davey RW. Antibacterial properties of propolis (bee glue). J.R Soc Med. 1990; 83:159-160.

Harish Z, Rubinstein A, Golodner M, et al. Suppression of HIV-1 replication by propolis and its immunoregulatory effect. Drugs Exp Clin Res. 1997; 23:89-96.

Khayyal MT, el-Ghazaly MA, el-Khatib AS. Mechanism involved in the anti-inflammatory effect of propolis extract. Drugs Exp Clin Res. 1993; 19:197-203.

Kujumgiev A, Tsverkova I, Serkedjieva Y, et al. Antibacterial, antifungal and antiviral activity of propolis of different geographic origins. J Ethnopharmacol. 1999; 64:235-240.
Ledon N, Casaco A, Gonzales R, et al. Antipsoriatic, anti-inflammatory and analgesic effects of an extract of red propolis. Chung Kuo Yao Li Hsueh Pao. 1997; 18:274-276.

Lin SC, Lin YH, Chen CF, et al. The hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries. Am J Chin Med 1997; 25:325-332.

Matsuno T, Jung SK, Matsumoto Y, et al. Preferential cytotoxicity to tumor cells of 3, 5-diprenyl-4-hydroxycinnamic acid (artipillin C) isolated from propolis. Anticancer Res. 1997; 17(5A):3565-3568.

Mirzoeva OK, Calder PC. The effect of propolis and its components on eicosanoid production during the inflammatory response. Prostaglandins Leukot Essent Fatty Acids. 1996; 55:441-449.
Mirzoeva OK, Grishanin RN, Calder PC. Antimicrobial actin of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria. Microbiol Res. 1997; 152:239-246.

Natarajan K, Singh S, Burke TR Jr, et al. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-Kappa B. Proc Natl Acad Sci. 1996; 93:9090-9095.

Ozturk F, Kurt E, Cerci M, et al. The effect of propolis extract in experimental chemical corneal injury. Ophthalmic Res. 2000; 32:13-18.

Park EH, Kahng JH. Suppressive effects of propolis in rat adjuvant arthritis. Arch Pharm Res. 1999; 22:554-558.

Rao CV, Desai D, Simi B, et al. Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical change and aberrant crypt foci formation in rat colon. Cancer Res. 1993; 53:4182-4188.

5.  Medical Research on Propolis

The development of modern medicine however has seen Propolis and many other natural remedies neglected and forgotten. It is really only in the last 20 -30 years that modern medicine, particularly in Eastern Europe, has again begun to use Propolis therapeutically, to study it and to appreciate its healing potential. Over the last 20 years much scientific and medical research has been undertaken into Propolis both in this country, America as well as East Asia, where the medical use of Propolis is common.

 

Propolis is a pure natural antibiotic.

The patient doesn't get immunity from this kind of antibiotic, allergic reactions are very rare, which can't be said for synthetic antibiotics. Recent research at the National Heart and Lung Institute in London has shown that the bio-flavonoids in Propolis are capable of destroying some bacteria that have now become resistant to modern synthetic antibiotics. Research has shown that it is impossible for bacteria to grow or adapt to Propolis.

 

Propolis has been shown to be effective against:-

 

BLOOD DISORDERS

Chinese researchers found it effective in treating hypertension, arteriosclerosis and coronary disease. European scientist V. Balalykin tells us that Propolis helps the white blood cells to engulf and digest bacteria and other waste products in the blood.

GASTRO INTESTINAL PROBLEMS

Russian scientist and doctors have shown that Propolis can prevent ulcer and abscess formation, as well as speeding up the healing process.

DERMATOLOGICAL DISORDERS

Research in America, Poland and Russia has shown that acne, allergies, herpes and other dermatological disorders have all responded to Propolis therapy.

BREATHING DIFFICULTIES

Russian Dr. J. N. Pavelenko uses Propolis for Asthma bronchiole (alcohol tincture). Medicine is taken orally, 20 drops in milk or camomile tea, half hour before meals, 3 times a day for two months. By using this treatment writes Dr. Pavlenko even the worst coughs and bronchitis can be treated.

 

6. PROPOLIS RESEARCH REVIEW

1. Propolis
· World propolis production is increasing substantially. Major producers include China, Brazil, US, Australia and Uruguay. Japan is a major consumer of propolis.

Flavonoids account for much of the biological activity in propolis. At least 38 flavonoids have been found in propolis and Brazilian propolis has some of the highest amounts of these essential flavonoids.

A large number of studies have shown propolis to be highly antimicrobial. Propolis has been found to have an inhibitory affect on at least 21 species of bacteria (including MRSA)19 species of fungi (including the causative organisms of thrush, ringworm and athlete's foot), 3 species of protozoa (including Giardia)1 and a range of viruses (including herpes and influenza). (see Section 6.1)

Propolis has been shown to have a range of other therapeutic properties, including antioxidant effects1 wound healing and tissue repair effects, gastro-intestinal effects, skin infection effects, anti-inflammatory effects, anaesthetic effects, effects on the immune system, cardiovascular effects and dental care effects. (see Sections 6.2~.12).

Because of the high levels of flavonoids found in propolis, the product has high value as an antioxidantifree radical scavenger in humans. Of particular interest is its ability to protect vitamin C from being oxidized or destroyed. (see Section 6.4).

Clinical studies have shown propolis to be effective in the treatment of bronchitis and similar disorders; influenza and herpes; ringworm and skin fungi; a range of dental disorders; skin ulcers, burns and abscesses; ear infections; giardia and colitis, hip inflammation; and vaginal and cervical inflammation. (see Section 7).

Propolis is known to cause contact dermatitis in a small percentage of humans. The dermatitis has been shown to be relieved once the skin is no longer in contact with the propolis product. It is therefore recommended that usage is ceased whenever there is an allergic reaction. (see Section8).

Contamination and short shelf-life is not a problem with propolis and propolis products, because of the substance's antioxidant and antimicrobial properties. Raw propolis should routinely be tested for lead contamination. (see Section 10)
PROPOLIS

2. Propolis Description

Propolis is a resinous yellow-brown to dark brown 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 changes consistency with temperature. At temperatures below 150C it is hard and brittle, but becomes more pliable and sticky at higher temperatures (25-450C). Propolis generally melts at 60-700C, although some samples have been found to have a melting point as high as 1000C (Krell, 1998).

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, drinks).

3. History of Use

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 12th century Europe describe medical preparations using propolis for the treatment of mouth and throat infections, and dental cares (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.

4. 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, 1998):

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 (ie, they do not have sugar molecules attached to their chemical structure). The majority of flavonoids found in plants are glycosides.

Flavonoids are thought to account for much of the biological activity in propolis (Grange and Davey, 1990), although other phenolic compounds are also involved. At least 38 flavonoids have been found in propolis, including galangin, kaempferol, quercetin, pinocembrin, pinostrobin and pinobanksin (Schmidt and Buchmann, 1992). 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. 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.

Studies indicate that the plant resins collected by bees are at least partially altered by bees prior to use in the hive.

5. 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).

6. Therapeutic Properties
6.1 Antimicrobial Effect

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 summarized in the following table (from Krell, 1996 and others):

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). Propolis has been found to inhibit the synthesis of protein by bacteria, which may account for at least some of Its antimicrobial effects (Simuth, et al, 1988).

6.2 Synergistic Effects

Most studies on the therapeutic properties of propolis have centered on the phenolic constituents (flavonoids and other phenolic compounds such as caffeic acid esters). Research has tended to isolate and test single substances in propolis. However, it is likely that the presence of a large number of compounds in propolis may produce a syngeristic effect greater than the sum of the effects of individual components (Houghton, 1998). Studies have shown that the flavonoids in propolis exert significant antibacterial activity, but that isolated flavonoids show reduced activity compared to whole product extracts (Bone. 1996).

Propolis has also been shown to have a synergistic effect with certain antibiotics, and to increase their effectiveness on some bacteria and yeasts some cases 100 fold (Kivalina and Gorshunova, 1973). Antibiotic-resistant strains of Staphylococcus were found to become sensitive to antibiotics in combination with propolis (Shub, 1981).

6.3 Antioxidant Effects

The flavonoids concentrated in propolis are powerful antioxidants. Antioxidants have been shown to be capable of scavenging free radicals and thereby protecting lipids and other compounds such as Vitamin C from being oxidized or destroyed (Popeskovic, et al. 1980).

It is probable that active free radicals, together with other factors. are responsible for cellular aging and degradation in such conditions as cardiovascular diseases, arthritis, cancer, diabetes, Parkinson disease and Alzheimer disease. Oxidatve damage may also result in poor liver function. Studies on rats in vitro show that propolis extracts protect against damage to liver cells (Baset, et al, 1996).

6.4 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).

6.5 Gastro-Intestinal Effects

Propolis has been shown to inhibit the development of externally induced stomach ulcers in rats
(Aripov, 1988). Flavonoid components of propolis have also been shown to have this effect (Ciaceri and Attaguile, 1972).

6.6 Skin Infection Effects
Propolis has been shown to be effective in inhibiting the growth of yeasts and fungi responsible for such skin infections as ringworm and athlete's foot (Metzner, et al, i979). Propolis compounds showing activity against these organisms are the flavonoids and caffeic acid derivatives.

6.7 Anti-Inflammatory Effects

Studies on mice have shown that extracts of propolis have an anti-inflammatory effect similar to that of indomethacin, a common drug used to treat inflammation. Again, flavonoids and caffeic acid are known to play a role in inhibiting the inflammatory response (Mirozeva and Calder, 1996).
6.8 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).

6.9 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 ant-tumour effect produced by propolis.

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 (Scheller, et al, 1988).

Propolis was shown to increase antibody formation between 2-3 times that of controls in pigs vaccinated with "BUK-628" live Aujeszky's disease vaccine with and without addition of propolis. Antibody formation reached its maximum in 14 days, and antibodies could be detected for up to 330 days. Propolis also enhanced production of plasmacytes in the lympholdal tissue of the spleen and lymph nodes (Karandashov, et al, 1977).

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).

6.10 Cardiovascular Effects

In mice1 a concentrated extract of propolis has been shown to reduce blood pressure, produce a sedative effect, and maintain serum glucose (Kedzia et a11 1988). Dihydroflavonoids1 as contained in propolis, have been shown to strengthen capillaries (Roger, 1988), and produce antihyperlipidemic activity (Chol, 1991). Propolis has also been shown to protect the liver against alcohol (ethanol) and tetrachloride in rats (Coprean,et al, 1986).

6.11 Dental Care Effects

In rats inoculated with & sobrinus, about half of their fissures were carious, while dental canes were significantly less in rats given water containing propolis extracy. 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). Propolis has also been shown to inhibit the growth of a range of bacterial organisms found in dental caries (Ota, et al, 1996).

7. Clinical Effects on Humans

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

7.1 Respiratory Infections

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, 1938).

7.2 Viral Infections

A clinical trial has shown a prophylactic effect against influenza infection in humans (Vosnjak, 1978). Mother clinical trial showed that infections of the common cold were shorter in duration and completely recovered within 3 days for patients treated with propolis, compared to 5 days for recovery for patients not given propolis. (Scheller et al, 1989).

A clinical trial conducted on dermatology patients showed a propolis cream had significant therapeutic effects against recurrent herpes (Herpes simplex Type 1) and Herpes zona zoster (shingles). The propolis cream reduced duration of lesions and pain, and increased interval between lesion episodes (Giurcaneanu, et al, 1988).

7.3 Skin InfectIons

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 0.3g 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).

7.4 Dental Treatment

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, 1988).

A double-blind clinical trial showed that a propolis mouthwash (10% tincture diluted l:5 with water) produced significant improvements In patients with gingivitis and periodontal disease. Patients were evaluated for plaque formation and inflammation of the gums (Schmidt. et al, 1980).
A clinical study used a paste made from propolis extract and zinc oxide on 150 teeth with indirect capping of deep cavities, and 50 teeth with direct capping. The results showed that the paste with propolis exerted effects similar to those of zinc eugenate, and were superior for healing compared to pastes based on calcium hydroxide (lonita, et a1, 1990).

A clinical study found propolis useful for the treatment of gum inflammation and oral mucosa, and also showed anti scarring effects (Gafar, et all 989). Another study showed similar results for periodontitis and suggested propolis be used in root canal fillings because of its bone-regeneration and anaesthetic properties (Kosenko and Kosotch, 1990).

7.5 Wound Healing and Tissue Repair

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 84 treated patients exhibited no clinical signs of the condition, 19 an improved condition (Korsun, 1983).

Propolis was used in a trial of hospital patients with infected wounds. The propolis improved wound healing rates, while at the same time reducing infection. Over half of infective bacteria were eliminated within 4 days. Propolis did not produce antibio~resistance strains of the bacteria (Damyanliev, 1982).

A study of topical application of propolis on wounds, burns and ulcers showed up to an 80% increase in healing rate compared to controls using routine healing regimes (Scheller, 1980).
Patients (229) with bums, clean wounds, infected wounds or abscesses / ulcers were treated with 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 38 days (Morales and Garbarino, 1996).

7.6 Ear Infections

Patients (126) suffering external otitis, chronic mesotypanic otitis and tympan perforation were treated 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).

7.7 Gastro-Intestinal Problems

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% versus 40% for Undazole at a higher concentration (30% propolis extract) (Mirayes, et a11 1988).

Propolis was used to treat ulcerative colitis and Crohn's disease in a double-blind clinical trial in Denmark. Improvement was noted inpatients with colitis, but no effect was shown against Crohn's disease (Stolko, et al. 1978).

7.8 Immune Deficiencv

A strong immune deficiency was found in 2 patients with alveolitis fibroticans. Treatment with a combination of 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).

7.9 Inflammation

Injections of an aqueous solution of propolis were used in the treatment of 22 patients with this hip joint disease caused by aseptic necrosis of the thigh bone. A further 32 patients with the same condition were given different forms of routine treatment. Significant improvement was observed In the patients given propolis (Przybylski and Scheller, 1985).

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).

8. 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 mutagenicity per SE for propolis has not been reported (Schmidt and Buchmann, 1992).

Contact dermatitis is a well documented allergic reaction to propolis, with appoximately 200 cases reported in the literature over the last 70 years (Hausen et al, 1987). Initial reports were made by beekeepers, who came into daily contact with the raw product. Allergic reactions are now also reported in the general population, due to the more wide-spread use of products containing propolis.

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 (Hashimoto, et al, 1988). Cinnamic acid derivatives have also been implicated (Scheller and Frosch, 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). Rare cases of oral inflammation and ulceration, mouth oedema (swelling) and stomatitis have been reported. however, as a result of oral ingestion of propolis (Hay and Grieg, 1990; Wanscher, 1978).

9. Commercial Use

Raw propolis is collected by beekeepers and sold in bulk to companies that refine the product and turn it into usable extracts. 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). In Japan, the use of propolis is permitted as a preservative in frozen fish (Irrell, 1996).

Tinctures and lozenges are popular treatment for sore throats, and tinctures are often used to treat Cuts, mouth sores and skin rashes. For internal use, 1-3mL does three times daily of a 1:10 tincture are typical, but higher doses can use used if necessary. Propolis tincture is normally diluted in water. producing a cloudy liquid. For external use, the 1:10 tincture is diluted in water, and used as a lotion or gargle (Bone, 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 (Irell, 1996).

10. FoodSafety

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 propol is. 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. Brazilian propolis is of the highest quality available where Chinese propolis has been noted for excessive lead.

11.Quality Control

No international standard exist for propolis. Official standards exist for propolis in several East European countries. Japanese standards for Propels offer some of the highest none official standards.

Bee Propolis Past to Present

Propolis has been used by man for thousands of years and recently has enjoyed a boom in popularity. 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 accredited to propolis. As humans, we may yet discover we've only just scratched the surface to the benefits of this resinous wonder.

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, to name a few.
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 is a sticky resin which seeps from the buds of certain trees and oozes from the bark of other trees. Although propolis is vitally important to the colony, there are usually just a few propolis gathering specialists in the hive.

The bees gather propolis, sometimes called "bee glue," and carry it home in their pollen baskets. There they are met by one or two other worker bees who help them unload. 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 protects the hive in two ways: First, it reinforces the hive itself; second, it protects the hive from bacterial and viral infection. And it is these latter properties which man has found so helpful through the centuries.

The reason propolis is such an effective protector is related to the diversity of flavonoids. Propolis consists of approximately 55 percent resinous compounds and balsams, 30 percent beeswax, 10 percent aromatic oils, and 5 percent bee pollen. Other constituents include flavonoids, amino acids, B vitamins, and most importantly, antibiotic substances.

Often called "nature's penicillin," bee propolis has effective antibacterial, antiviral, antiseptic, antifungal, and antibiotic-properties. These protective and healing properties have been conclusively demonstrated in numerous studies all over the globe.

Tuberculosis

In the former Soviet Union, V.H. Karinova and E.l. Rodionova conducted a study on 135 patients suffering from various forms and stages of tuberculosis. Their patients' ages ranged from six to 50. Patients were given bee propolis three times daily for four to 10 months depending upon response to treatment. By the end of the study, all but 12 of the patients had improved dramatically, including some patients going into regression. The12 who did not respond favorably all suffered from kidney tuberculosis.

Ulcers

In Romania, Drs. A. Vasilca and Eugenia Milcu conducted a study on the therapeutic properties of propolis on ulcers. Thirty four patients with chronic ulcers were given extracts of propolis daily for two weeks. The results were impressive, with 28 patients completely recovering and six cases dramatically improving. Tissue biopsies were conducted on some of the patients, which confirmed the regenerative effects of bee propolis.

Mitosis

Medical researchers N. Popovic and N. Oita of Rumania published a report on the effects bee propolis has on mitosis (the process of cell division). They reported that a tissue never becomes entirely malignant; it always contains some normal cells, but the activity of the normal cells is affected and even repressed by malignant cells. Bee propolis favors the activity of normal cells by repressing malignant cells, which helps the tissue to reestablish its normal condition. Constituents of propolis have a mitodepressive effect (depression of the proliferation of cancerous cells) on cells deranged by malignancy.
Colitis

In Bulgaria, Dr. S. Nikolov, et al, investigated the efficacy of bee propolis in the treatment of acute and chronic colitis. Forty five patients, both men and women aged 20 to 65 years old and suffering from either acute or chronic colitis, took part in the study. They were given extracts of bee propolis three times a day before meals. In 43 of the patients results were positive, with 26 showing very good response, 12 showing good response, and five showing satisfactory. Only two patients showed no improvement. In most cases, pain began to diminish in seven days, disappearing on the nineteenth or twentieth day.

Immune System

Perhaps the most broadly investigated and widely accepted attribute of bee propolis is its immune-boosting activity. It is a natural, broad-spectrum antibiotic that activates the thymus gland. Bee propolis not only prevents infectious diseases, but clears them from the system, as well.
As demonstrated in numerous experiments, propolis has the ability to directly destroy bacteria, viruses, and fungi, even penicillin-resistant staphylococcus.

Bee propolis is formidable against viruses. This trait is attributed to the bioflavonoids present in propolis, which have a protective effect against viral infections. Viruses are enclosed in a protein coating. As long as it remains unbroken, the infectious and dangerous material remains imprisoned and is harmless to the host organism. Unfortunately, within the host their are enzymes which remove the protein coating, thus releasing the harmful material to wreak havoc within the system. With the presence of bee propolis in the system, however, this doesn't occur. The bioflavonoids inhibit the enzymes from removing the protein coating, keeping the viral material locked inside. These same flavonoids maintain the protective coating around the virus, thus rendering it inactive. With the presence of the bioflavonoids, the host virtually becomes immune to the virus.

Another way in which propolis aids the immune system is its ability to strengthen phagocyte activity. Phagocytes are cells that are able to surround, engulf, and digest microorganisms and cellular debris. This increase in activity with the introduction of bee propolis was observed and documented by a number of Soviet and European scientists.

The Power of Propolis

The power of propolis is wide-ranging and of immense benefit to humans, as well as to its creator-the little honey bee. People suffering from high levels of blood fat can benefit from taking bee propolis. At the Worker's Hospital of Lian Yun Gang, Jiangsu Province in the People's Republic of China, Dr. Fang Zhu chose 45 patients suffering from hypertension, arteriosclerosis, and coronary heart disease and gave them 300 mg of bee propolis three times a day for 30 days. At the end of that period all patients showed a significant reduction of blood fats and improvement in related disorders.

Another benefit of propolis is its inhibitory effect on certain prostaglandins, which it accomplishes by blocking the enzymes that form specific prostaglandins. This can be of immense benefit to those suffering from aches and fever, which are caused by prostaglandins. Bee propolis acts in nearly the identical way aspirin does by blocking the same enzymes, yet without the negative side effects you can get with aspirin.

This enzyme-blocking, prostaglandin-inhibitory effect is also beneficial to the mouth and throat. For instance, a leading cause of dental problems is the erosion of the gums and tissues that line the tooth sockets. Inflammation and infectious bleeding can cause a weakening of the bone structure and tooth loss. But propolis, by blocking specific enzymes, prohibits the formation of the prostalandins which cause the inflammation, bleeding, and eventual decomposition. At the same time, propolis actually stimulates other specific enzymes which strengthen the walls of the blood vessels in the gums, thereby having a twofold effect on the mouth.

When inflamed and sore, the throat responds favorably to propolis, and for the same prostaglandin inhibition reasons. By inhibiting prostaglandin formation, inflammation recedes and diminishes.

Another attribute of bee propolis is its ability to correct and stabilize proper protein metabolism. A team of physicians at the Institute of Radiology at Serajevo, Yugoslavia treated patients who were suffering from radiation complications. These patients had serious liver damage caused by improper protein metabolism and X-rays. The patients were given bee propolis for two months. Another group of patients, also suffering from radiation complications, were given a placebo. At the end of two months, those taking bee propolis had significantly improved, with some patients' symptoms completely disappearing. No improvements were observed in the group given the placebo.

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