Propolis combines meanings of two words, Pro (front) and Polis (city) originated from the ancient Greek which means protection against harmful invaders from outside. Propolis is sticky liquid natural substance made from bees by ripening the mixture of bee’s wax and/or saliva with wood veneer in beehives. It protects themselves from harmful bacteria and/or viruses and maintains their survival, proliferation, and clean environment. Bees have used Propolis as their self-treating substance to protect their species from viruses, bacteria, and fungi. In normal beehive, there is no virus, bacterium, and fungus because of Propolis. Unlike honey or royal jelly, only small amount can be harvested and it is unable to synthesize artificially. The history of Propolis goes back to approximately 300 B.C. There is a record that Egyptians have used Propolis to prevent decay of mummy and treat the wounds and inflammations. It has been also used as natural preservative and medical treatment substance in many other countries. However, it became less popular compared to penicillin which was more convenient with fast effect through the World War I and II. But since 1960s, Propolis got highlighted again for other problems from the resistence of antibiotics and attracted lots of researchers.
From discovering that there is no bacterium on bee’s body, Dr. Remmy Sauvin has found this natural antibiotic compound. Afterwards, it was proved to contain 150 compounds and 22 minerals by compound analysis. It is composed of 50% of resin, 30% of wax, 10% of oil compounds such as essential oil, 5% of pollen, and 5% of organic compounds and minerals. Out of these, flavonoid is the key compound of Propolis.
In 1970, Dr. U.H.Villanueva has reported that there are 18 flavonoids in Propolis at the science academy of the former Soviet Union. Also, he has scientifically proven that it is the flavonoid compound that makes the beehives sterile by discovering galangina pinocemorina, an antibiotic compound of Propolis. Flavonoids remove peroxide wastes by antioxidant activity.
According to a German researcher, Dr. Bent Havesteen, flavonoids have superior anti-viral activity because dozens of flavonoid compounds can serve as a protective wall against bacteria.
It was reported that the higher concentration of Propolis has stronger inhibitory activity onStaphylococcus aureus, Salmonella, Bacillus subtilis, Streprococcus pluton, and others.
As time passes by, purified Propolis became more popular for numerous purposes including cold medicine, tooth paste, mouth wash, lipstick, cosmetics, and others
The major chemical compounds in the Propolis are flavonoids, phenolics, and terpenes. Flavonoids include quercetin, apegenin, galangin, kaempferol, luteolin, pinocembrin, pinostrobin, and pinobanksin. Phenol ester included in the Propolis is attracing lots of interests for numerous diseases including spinal damages.
The precise mechanism of anti-bacterial activity is unknown. However, Propolis has shown anti-bacterial effect both in animal and human studies.
Propolis has shown anti-viral activity in animal and human studies to treat HIV, common cold, blister-virus diseases. In recent in vivo and in vitro studies, it has been shown that the anti-viral activity of Propolis prevented the absorption of virus by host cells infected by HIV-1.
The anti-oxidant activity of Propolis was known to be contributed by caffeic acid phenethyl ester (CAPE) in Propolis.
CAPE is also known to have anti-cancer activity to implicate the possible anti-cancer activity of Propolis. Propolis extracts were provided to the mice and it suppressed the colon cancer induced by azoxy methane. Also, it was reported that cinnamic acid derivative obtained from bee wax has suppressed the growth of human cancer cell line in vitro.
CAPE is also known to have immunomodulating activity. Hydrophilic derivative of Propolis has been known to have non-specific anti-tumor activity via acrophagic activity in mice with immunomodulating action.
CAPE inhibits the lipoxygenase pathway of arachidonic acid which is the final product of inflammation reaction and suppresses the activation of a nuclear transcription factor, NF-Kappa B. Also, it inhibits the generation of reactive oxygen species (ROS). Propolis extracts have shown anti-inflammatory activity in animals with arthritis. In a recent study, methanol and water extracts of Propolis have inhibited the activity of nitric oxide (NO) in vitro. Therefore, Propolis is considered to possibly have direct anti-inflammatory activity.
The amazing part of anti-bacterial activity of Propolis is that it kills the bacteria while suppressing the replication of viruses that cause diseases. Most antibiotics nowadays have no effect on viruses. The antibiotic compound in Propolis is known as flavonods. There are many publications on the anti-bacterial activity of Propolis. However, its mechanisms of action vary by the origins and the extraction methods. Propolis exhibited strong anti-bacterial effect on Trichopohyton, Epidermophyton, and Mycrosporum. When its ethanol extracts were applied to the colony, it strongly inhibited the growth of gram-positive bacteria including Staphylococcus aureus, Enterococcus spp. Corynebacterium spp. Branhamella catarrhalis, and etc. This proved the selective inhibitory activity of Propolis on gram-positive bacteria. The whole ethanol extracts have shown even stronger anti-bacterial activity compared to the single separated flavonoid. Also, the anti-bacterial activities with different origins of harvest differed even on the same bacteria. In general, the Propolis with stronger flavor had stronger anti-bacterial effect. The mixture of various Propolis from numerous regions have exhibited higher anti-bacterial effect on most of the bacteria compared to the single Propolis from one region. It was pinocembrin that inhibited the growth of S. aureus the most. Especially, the antibacterial activity of Propolis barely changed when heated at 100℃ for 3 min. In a separation identification of anti-bacterial compounds in Propolis, it has been proven that pinosylvin and cinnamylidene acetic acid are the compounds with anti-bacterial activity. In Korea, it is listed as “Propolis extract product” in the health functional food in notification of “Notification on the Health functional food” by “Health functional food act” announced in 2003. As it complies with the noticed standard qualification, its “oral anti-bacterial activity” and “anti-oxidative activity” are accepted.
It was proved that the anti-oxidative activity of Propolis is contributed by phenolic compounds in many studies. It was discovered that the more hydroxyl groups are located in the structure of the phenolic compound, especially in ortho- or para-positions, the more anti-oxidative activity is increased. Most of the oxygen absorbed into the body is reduced to the water (H2O) by metabolism. However, some of them are converted to the reactive oxygen species (ROS) with great reactivity. ROS includes superoxide radical (O2), hydroxyl radical (HO), hydrogen peroxide (H2O2), singlet oxygen (1O2), and etc. ROS destroys cellular components such as lipid, protein, sugar, and DNA in non-selective, irreversible manner. It causes all sorts of diseases such as stroke, cancer, atherosclerosis and cardiovascular disease, chronic inflammatory disease such as rheumatism, autoimmune disease, and others as well as aging and dementia. Within the human body, there is a protective system to prevent this oxidative stress. The system is composed of antioxidant compounds such as α-tocopherol, ascorbic acid, and glutathione and antioxidant enzymes such as superoxide dismutase (SOD), catalase, and peroxidase which remove the reactive oxygen to protect the organism. Oxygen which is essential for the maintenance of life is used to generate energy via respiration. When oxygen is converted to reactive oxygen such as superoxide radical, hydroxyl radical, peroxide, and singlet oxygen by physical, chemical factors and enzymatic reduction metabolism, it causes critical damage to the body leading to aging, cellular damage, cancer, and degenerative nerve disorders. In normal cells, free radicals, reactive oxygens, and peroxides are generated in metabolic processes. In the human bodies, antioxidant enzymes such as SOD, CAT, GPX, GST, and GR exists as a protective mechanism against them. Aerobic animals acquire energy by respiration with oxygen as an electron receptor. Compared to other effective anti-oxidant agents, Propolis was more potent compared to vitamin E.
Propolis didn’t induce resistance of antibiotics to bacteria.
It is known thatPropolis induces regeneration of the damaged tissues and activate cells. When Propolis was used on wounds, burns, and ulcers, the therapeutic effect was higher by 80% at the largest compared to the control group of general method. Propolis not only improved the treatment of burns but also stimulated various enzyme system, cellular metabolism, circulation and collagen synthesis. These are contributed by arginine and proline included in the Propolis which stimulate dell division and protein synthesis as well as reinforcing the collagen and elastin. When Propolis and urea was applied to the burns in mice, tissues began to regenerate within 2 weeks.
Also, Propolis helped the regeneration of bones and cartilages. No resistant strain appeared while using Propolis which implicates the benefits of Propolis over antibiotics which cause resistance to the bacteria.
When Propolis was used in surgical wounds, burns, and ulcers, faster treatment was observed by 80% at maximum compared to the typical treatment. When Propolis was injected to the hip pivot joint of patients with Leg-Clave-Perthes disease, it brought better therapeutic effects compared to the typical treatment.
Substantial amounts of amino acids including arginine and proline are detected in Propolis. It is considered that these two are the key in the benefits of Propolis promoting protein synthesis and mitosis as well as stimulating synthesis of collagen and elastine to help the wound healing process. Propolis also promotes the metabolism and embryonic cell division. When it was injected in mice, cellular energy metabolism was reinforced.
It was known that Terpene compounds in resin inhibit the obstructive factors of chemotherapy including hair loss, gastric discomforts, liver and gastric dysfunction, and others when coadministered with Propolis. Anti-cancer agents have cellular toxicity. When reactive oxygen species are generated within the cells, Propolis removes these reactive oxygens to relieve the side effects. The ethanol extracts of Propolis has deformed the human liver cancer cells and cervical cancer cells as well as suppressing their growths. The compounds showing these effects include quercetin, caffeine acid, and clerodanne diterpendoid. The latest one shows selective toxicity on abscess cells. Propolis has shown cytotoxicity and growth inhibition on hamster ovarian cancer cells and mouse sarcoma (tissue related to cancer) abscesses in vitro. Propolis has shown cytotoxic activity on both human and animal cell cultures including breast cancer, melanocytoma, rectal and kidney cancer cell lines. It was confirmed that these effects are induced by caffeic acid phenethylester (CAPE).
The tumor mice administered of Propolis extracts showed much higher survival rate compared to those administered of bleomycin, an anticancer agent. CAPE administration has suppressed various cancer cell lines including the human brain cancer. Here, melanocytoma has shown the highest responsiveness. As a result, the role of CAPE as an abscess preventive agent was possibly suggested. Small amount of CAPE was also administered to mice and it showed strong inhibition of aging process which is essential in the progress of abscess. Based on this, it was proved that CAPE may be a potent chemical preventive agent for these diseases including cataract with potent inflammation/aging suppressants.
A compound called Artepillin C was separated from Propolis. In vitro, it was found that it has cytotoxic activity on human stomach cancer cell lines, human lung cancer cell lines, and mouse rectal cancer cell lines. CAPE has not only exhibited selective toxicity on influenced by tumor growth factor genes but also suppressed the growth of chemical-induced abscess in mice. CAPE selectively suppressed the DNA synthesis and growth of deformed cells and even killed them in high concentrations. Caffeic acid extracts of Propolis which decrease the onset rate of skin abscess in mice also showed the same inhibitory action on the DNA synthesis. Propolis has cytotoxic activity on tumor cells and it is expected to be contributed by flavonoids. Propolis extracts rich in flavonoids and phenolic compounds have suppressed the growth of cervical cancer cells and nasopharyngeal cancer cells in vitro. The derivatives of the caffeic acid are also known as major active compounds of Propolis inhibiting cellular activities.
Radiation treatment is becoming more widely used in diagnosis and treatment of cancer. The side effects in normal tissues by radiation, however, can bring other diseases not intended in the original treatment. There is a report that Propolis has anti-oxidant activity and radiation-protective effect. When the compositional changes of trace elements in liver tissues were compared between the control group and the Propolis group, the essential elements including Fe, Mg, Ca, Co, and Ni have increased after treatment. On the other hand, toxic elements including As, Cd, and Pb have decreased in Propolis-treated group after radiation. As a representative of increased elements, the increase in Fe is considered to have come from the role of Propolis preventing the deficiency of iron. Fe in the hemoglobin in the blood stream helps provide oxygens as an essential element related to anemia. Propolis is involved in the catalytic response removing reactive oxygen, superoxide radical, and H2O2 mediated by SOD and CAT. It was also observed in the Propolis-treatment group that radiation-induced injuries in nuclear membrane and mitochondria which are in direct contact with oxygen were significantly reduced.
In a microarray test to see the changes in genetic expression, over twice increase or decrease in genetic expression was observed in Propolis-treatment group and control group. It was reported that radiation-induced injuries are more significant in areas around blood vessels with more oxygen in liver tissues. In another experiment, more cells were destroyed around the deep vein in liver cells, however, little damage was observed around the central vein in Propolis-treatment group. In stomach and intestine tissues, radiation-induced injury was observed in surface mucosal cells, goblet cells, and chief cells. On the other hand, no specific behavioral change was observed from Propolis. Especially, significant damages were observed in mitochondria and nuclear membrane which are the sources of energy. On the other hand, less cellular damages were observed in the group treated by Propolis.
Stresses from alcohol, smoking, and stress give damage to DNA. Also, environmental pollution, drug abuse, and lots of additives give damage to the chromosome. Damaged genes can be somewhat treated by trace compounds such as vitamin E and selenium which are included in Propolis. Also, flavonoids included in Propolis excrete toxic genes from the cells. Complex of 128 flavonoids in Propolis maintain the balance between tumor-suppressive genes and tumor-proliferating genes by supporting tumor suppressive genes.
In mice, concentrated Propolis extracts have not only lowered the blood pressure but also maintained the blood glucose level. And dihydroflavonoids included in Propolis reinforced the capillary phenomenon and attenuated the hyperlipidemia in blood stream. Another experiment was conducted to see the effects of Propolis in mice with artificially induced heart disease. At this time, doxourubicin was used to induce heart problem by oxidative stress. Various biochemical assessments were performed including autopsy of cardiac muscles. It was comparable to the rutin, a cardiac protective flavonoid in Propolis. From this, it was found out that Propolis protects heart from oxidative stress. When cholesterol is combined to the reactive oxygen in the blood, it becomes lipid peroxide. It adheres to the vascular endothelial walls to bring negative effects on the blood circulation by decreasing the elasticity of the vascular wall. Flavonoids included in Propolis prevent the hardening of vascular wall by removing reactive oxygen species.
It was understood that Propolis extracts induce activy of scavenger cells involved in human immune system. Propolis activates immune cells secreting cytokines to prevent abscess. Immunofacilitation has been proved in guinea pigs. Those administered of Propolis extracts had 3 times more splenocytes producing antibodies compared to the control group. Propolis increases the cytotoxins of NK cells in vitro.
Propolis sample was orally administered to the mice followed by peritoneal injection of carbon tetrachloride to induce lipid peroxide. From the liver fraction of the mouse, MDA contents were measured. In lipid peroxide group administered of CC14, MDA contents have increased more than twice to 1.7nmol. However, Propolis-treatment group showed 70% decrease to 1.09nmol, generally to 1.08nmol. Administration of Propolis has reduced the lipid peroxidation induced by Salmonella in the liver of mice.
It was observed that each Propolis sample has suppressed the mutation induced by NDP (4-nitor-phenylenediamine) in each strain including S. typhyuium TA98 and others in a dose-dependent manner. Especially strong anti-mutagenic effect of almost 100% was observed at the concentration of 500µg/plate.
A number of publications implicate the anti-inflammatory action of Propolis. It has shown suppressive actions on at least 29 bacteria (including MRSA), 24 germs (including microorganisms in thrush, ringworm, and athlete’s food), 4 protozoa (including Giarrdia) and viruses (including Herpes and Influenza). Even though other phenolic compounds are also included, it is considered that flavonoids are the key to explain many of biological activities of Propolis. In Propolis, at least 38 flavonoids were discovered including galangin, kaempferol, quercetin, pinocembrin, pinostrobin, and pinobanksin. In another study, the minimum inhibition concentration of Propolis was 400 times higher in B. subillis and S. aureus.
Pinocembrin, galangin, caffecic acid, and ferulic acid are the anti-inflammatory compounds in Propolis. Germicidal compounds include pinocembrin, pinobanksin, benzyl ester, sakuranetin, and pterostibene. Antiviral compounds include caffecic acid, luteolin, and quercetin. Propolis is known to inhibit the protein synthesis in bacteria.
Propolis has been used to treat mouth ulcer, peptic ulcer, and ulcerative colitis. Since flavonoids play an important role, no importance was placed on the concentration of therapeutic compounds and astringents. Propolis has been mostly used in Russia and Austria to treat the peptic ulcer and gastric ulcer. In Denmark, it has been effective in patients with ulcerative colitis and ulcerative colon cancer.
Even though flavonoids in Propolis showed significant anti-bacterial activity, the effect of each individually separated flavonoid was significantly lower compared to the whole extracts. For example, when Propolis was tested on a single Herpes virus, synergic effects were observed in all the flavonols tested. Also, 10~100 times higher synergic effect was observed in some of the bacteria and yeasts. The antibiotic-resistant strains including Staphylococcus responded sensitively to the antibiotics combined with Propolis. It has been shown that ethanol extracts of Propolis have significant synergic effect with Streptomycin and Cloxacilin as well as other antibiotics except for amphicillin.
Flavonoids concentrated within Propolis are potent anti-aging agent. Anti-aging agnets remove free radicals to prevent other compounds such as lipids and vitamin C from being oxidized or destroyed. The clearance of reactive oxygen species by ethanol extracts of Propolis has been proved by electron spin resonance spectra. Propolis extracts have also shown similar activities in other types of oxidizing agnets. This anti-aging property is contributed by removal of reactive oxygen species on alkoxy group. Propolis is also often compared with vitamin E for its anti-aging activity observed in animals fed on highly-unsaturated fatty acid diet. Propolis has shown more significant anti-aging effect compared to vitamin E. Together with other factors, active free radicals can be responsible for aging and degeneration of cytoplasm leading to cardiovascular disease, arthritis, cancer, diabetes mellitus, Parkinson’s disease, Alzheimer’s disease, and others. Also, damages from aging can bring poor liver function.
Anti-influenza activity has been observed in mice treated by Propolis prior to infection to show 40% of survival rate. Some Bulgarians have insisted that this protective effect is attributed to the activity of macrophages. In other experiments in mice and dogs, the effect was far more significant when Propolis was used before viral infection. These results show that the optimal anti-viral effect is obtained when Propolis is used both before and after the viral infection. The same was observed in another in vitro study using Hong Kong Influenza A. Propolis has local treatment effects on acne, psoriasis, periodontitis, and others. Also, successful application of Propolis on toe infection was even more attributed to the immunofacilitation and anti-viral effect. Especially it was proved to be more effective in upper respiratory tract infection such as tonsillitis, sinusitis, and pyogenic otitis in children infected by Influenza. Children treated by Propolis were completely cured in 3 days while those not treated were cured in 5 days.
For its strong antibiotic activity, Propolis has been well known as a natural antibiotic agent. Numerous studies have shown inhibitory effect of Propolis on various microorganisms. It has been found that Propolis has strong inhibitory action on 25 types of bacteria out of 39 tested. In vitro, Propolis has inhibited the growth of Aspergillus which is one of respiratory fungi by reducing the synthesis of toxin for 10 days at maximum. However, high concentration of Propolis has stopped the growth of fungi. Pinocembrin, a sort of flavonoid, has exhibited germicidal activity in vitro. These studies have shown that Propolis can enhance the activity of certain antibiotic compounds, even to 100~101 times on bacteria and yeast in vitro. Antibiotic-resistant Staphylococcus Aureus was responsive to antibiotics such as erythromycin, tetracyllin, and penicillin when combined with Propolis. In a study by Rumanian dermatologic clinics, it was reported that Propolis cream has reduced the treatment period and pain when used to treat Herpes Zoster as well as increasing the time to relapse.
Propolis and some of its compounds have shown strong analgesic activity which was 3 times higher than cocaine and 52 times higher than procaine in several studies on rabbit cornea. This analgesic effect is attributed to pinocembrin, pinostrobin, caffeic acid ester, and others. It explains why Propolis has been used to treat the wounds in mouth and throat for several generations.
The antibiotic activity, anti-inflammatory activity, local anesthetic activity, and anti-ulcer activity of Propolis play an important role in protection of mouth and teeth. In Rumania where Propolis was used to treat chronic mouth ulcer, it has been found that it is effective in not only periodontitis and inflammation in oral mucosa but also prevention of wounds. From a study in Russia, it was highly recommended to use Propolis in filling the root of teeth for its anesthetic effect and bone regeneration. In another study using Propolis and zinc oxide paste on pulpitis, generation of dentin and mineralization were observed. Some experts said that it induced closer similarity to the oral issues when compared to other pastes. A blinded clinical trial was conducted by Propolis toothpaste on patients with periodontitis and gingivitis. Formation of plague and alveolitis was evaluated after 4 weeks to see a surprising result which was measured by cytologic study on alveolar epithelium. Dedayed tooth tissues were regenerated and inflammation was decreased by treatment of Propolis. In mice injected by Staphylococcus, half of the cracks in teeth were decayed. On the other hand, it was observed that cracks were less decayed when Propolis-containing water was provided. No toxicity of Propolis was observed in the growth of mice.
Propolis has strong activity against hemacytozoon and trichomonas, a protozoan causing vagomotos. Clinical effectiveness of Propolis on pyogenic vaginitis has been verified. Total 90 patients with vaginitis and cervicitis caused by Streptococcus pyogenes have been treated by 3% ethanol extracts of Propolis and over 50% of patients achieved favorable outcome. Similar treatment was tested on patients with acute cervicitis caused by various parasite infection for 2 years. Patients were randomly assigned into two groups, control and treatment group. Vaginal band with 5% Propolis was used by the treatment group daily. The number of parasite was decreased in the treatment group at the end of treatment. 90% of patients were completely cured in 10 days.
Propolis has shown no toxicity in human or mammal when not administered too much. LD50 (Lethal Dose 50%) in mice is 7.340mg/kg. Oral administration of 1,400mg/kg daily for 90 days in mice caused no change in clinical appearance, activity, urine, body weight, and mortality. Compounds included in Propolis are “Generally Recognized As Safe” by FDA. Propolis can increase the sensitivity so caution is needed for patients with allergy, especially those with the history of skin rash. It has been known to induce contact dermatitis in a few persons which is relieved when not contacted by Propolis products anymore. Therefore, it‘s better to stop the use when an allergic reaction is observed. Little is known about the toxicity of Propolis. However, it is known as skin sensitinogen. Contact dermatitis is the representative allergic reaction of Propolis reported by approximately 200 documented cases in the past 70 years. Caffeic acid and its derivatives are confirmed as major allergens. The precursor of cinnamic acid is also related. 7% of patients with eczema are reported to be sensitive to Propolis. However, in a sensitivity study on 1,558 healthy volunteers, only 0.64% showed sensitivity.
|Physiological functions||Related diseases|
|Sterilizing, anti-bacterial effect||Stomatitis, periodontitis, pneumonia, cystitis, diarrhea, burn, wound, etc.|
|Anti-viral effect||Hepatitis type B & C, common cold, influenza, etc.|
|Anti-inflammatory effect||Alcoholic hepatitis, chronic sinusitis, chronic cystitis, etc.|
|Anti-allergic effect & immunomodulation||Atopic dermatitis, pollen disease, asthma, rheumatism, etc.|
|Vascular reinforcement and modulation of blood circulation||Hypertension, hypotension, anemia, stroke, sequel, cerebrovascular dementia, etc.|
|Improvement in endocrine system and metabolism||Diabetes, weight loss of exhaustion, menstrualpain, post-menopausal disorder, etc.|
|Stress relief||Autonomic dysfunction, shoulder pain, etc.|
|Tissue regeneration||Gastric ulcer, ulcerative colitis, post-operational recovery|
|Removal of reactive oxygen||Gastric ulcer, ulcerative colitis, post-operational recovery|
|Analgesic effect||Neuralgia, arthritis, late-phase cancer, etc.|
It is contraindicated to those with hypersensitivity to the components of honey. Pregnant and lactating women also should avoid the use of Propolis.
Hypersensitivity reactions such as dermatitis, rhinitis, conjunctivitis, skin rash, and others have been reported. No event has been reported for overdose administration of Propolis.