PROPOLIS RESEARCH

Numerous research data is indicating that propolis has the anticancer potential in preventing and therapy of tumor diseases.

Chemopreventive antioxidant
Native propolis has strong antioxidant effect. The genetic method of DNA chips at the “Ruder Boskovic” Institute in Zagreb showed that it explicitly amplifies the gene whose lack leads to appearance of reproductive organs cancer, lungs cancer and lymphatic system cancer. Propolis also protects from the occurrence of stomach cancer, liver cancer, colon cancer, kidney cancer and skin cancer. During chemotherapies it protects kidneys and heart from acute damage with cytostatics (the cisplatin).

Anticancer potential
Method of DNA chips shows that the native propolis stops cancer and metastasis progression and also kills tumor and abnormal cells, but not healthy cells. In brain tumor (gliom) it stimulates the organism to produce the medicine on its own (the immunosuppression therapy). Radiation and cytostatics in the combination with propolis more efficiently prevent cancer progress and metastasizing, and side effects are considerably milder.

Preliminary tests
Influence of native propolis on tumor of milk gland has been tested on mouses at the “Ruder Boskovic” Institute in Zagreb. Results show that the native propolis slows down the progress of tumor and in combination with the cytostatic, anticancer effect is much more expressed. Best antitumor effect is achieved when native propolis is taken two weeks before the appearance of tumor, and then continued together with the cytostatic, on which also indicates the genetic method of DNA chips.
Research of influence of native propolis on blood and appearance of metastases is continuing.

Medicine still doesn’t have successful cure for many viral illnesses. In the struggle against viruses, best results were attained by the use of prophylactic procedures, first of all the vaccination.
Good experiences with propolis in most frequent viral illnesses (cold, flu) contributed to testing of it’s influence on different viruses. Research undoubtedly indicates that propolis has indirect and direct effect - direct antiviral effect and indirectly it’s stimulating specific immunological defenses.

The indirect antiviral effect is based on the activity in viruses DNA. In some sorts (Herpes simplex, influenza, Herpes genitalis, Herpes zoster, Variola vera major, reo-virus etc.) it prevents its replication (in other words the multiplication inside the cell) and it also reduces the DNA synthesis that manifests itself in decrease of viral activity (1,2,3,4). In some oncogene viruses its interrupting transformation of the healthy cells to carcinogenic cells by means of decomposing their DNA (the fragmentation) and at the same time moves the mechanism of apoptosis with reference to death of transformed station (5,6,7). Research at the “Ruder Boskovic” Institute in Zagreb confirms that native propolis also kills tumor cells and deformed cells (apoptosis), but it doesn’t effect healthy cells.

The base of indirect effect is specific strengthening of the immunological system, which is obvious in increased number of lymphocytes and antibodies as an answer to viral infections (8). It is interesting that the vaccine (weakened viruses) in combination with propolis is more efficient in raising the immunological defense than the vaccine itself (9).

Clinical research showed faster process of recovery in genital herpes in men and women by local use of greases with propolis substances than with the medicine acyclovir (10). In case of cold virus taking of propolis is accelerating the time of recovery by 2.5 times (11).

Research is unequivocally indicating that propolis, as the mixture of about 300 compounds, is more efficient against viruses than his single compounds (12). Samples of propolis from different geographical areas have different chemical structure, but the difference in biological effects is insignificant (13). Thats why the healing value of propolis is important as mixture of all natural compounds which plants have built in it (native propolis) and not by isolating single compounds or mixtures of some compounds (extracts of propolis).

Years-long results of questionnaire for people who preventively used NATIVE PROPOLIS confirm the absence of viral illnesses (colds, flu) and faster recovery when they used it at an early stage of illness. It is interesting that with native propolis in few cases of the mononucleoses illness (Epstein-Barrov virus) symptoms of illness were mildly expressed. Clinical results showed slight enlargement of specific parameters and the recovery period was considerably shorter. NATIVE PROPOLIS is powerful but harmless natural preparation for health preservation and recovery in viral illnesses.

LITERATURE:
1. Isr Med Assoc J 2002 Nov;4(11 Suppl):923-7.
2. Drugs Exp Clin Res. 1997;23(2):89-96.
3. Microbiologica. 1990 Jul;13(3):207-13.
4. J Nat Prod. 1994 May;57(5):644-7.
5. Arch Virol. 2001 Aug;146(8):1517-26.
6. Mol Carcinog. 1991;4(3):231-42.
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10. Phytomedicine. 2000 Mar;7(1):1-6.
11. Otolaryngologia Polska 1989;43(3):180-4.
12. J Nat Prod. 1992 Dec;55(12):1732-40.
13. J Ethnopharmacol. 1999 Mar;64(3):235-40

For centuries propolis is being mentioned as the strengthener of immunological system. Newer researches are undoubtedly confirming such traditional experiences (1). Results are indicating that propolis amplifies immunological mechanisms for the production of specific and nonspecific defensive matters with which it is confronting illness and interrupts its progress, independently of native and acquired immunological capacities. Professionally, such effect is defined as immunomodulational or immunoregulational activity, and popularly like the strengthening of immunological system.

It has been proved that propolis in vitro prevents the growth of bacterium by not allowing dividing of bacterial stations (2). But propolis in vivo (in the organism), stimulates the immunological system for production of the specific and nonspecific matters from the macrophage which stops the illness, even in cases when in vitro propolis does not function on some bacterias (3,4). Which is why in bacterial inflammations the activity of antibiotics in the combination with propolis is more efficient than antibiotic alone (5,6).

In viral illnesses propolis is directly functioning on viruses by not allowing their multiplication and at the same time it encourages the immunological system on the accelerated production of antibodies (7,8,9,10,11).

In tumor illnesses it encourages immunological system on the strengthened activity of killer-cells and other specific and nonspecific defensive matters and at the same time moves the death mechanism of tumor cells (1,12). Its antimetastasis characteristics are also binded to the immunological activity (13).

Protective activity of propolis in radioactive radiations is manifested by stimulation of macrophage to produce interferons and specific cytokins which points to the immunological reaction of organism (14).

In some parasites which are causing inflammatory bowel disease, prevention with propolis significantly calms down the inflammatory process, which happens because of increased quantity of interferons in blood. That’s why the combination of medicine (the antiprotozoic) and propolis is more efficient than the activity of the single therapeutic (15).

Research with genetic method of DNA chips at the “Ruder Boskovic” Institute in Zagreb proved that native propolis eliminates all noxious substances (carcinogenic, poisons, free radicals, pollutants) introduced or created in the organism, and repairs damage in cells. Excellent years-long experiences in health protection with native propolis are only confirming the scientific facts.

LITERATURE:
1. J Ethnopharmacol. 2007 Aug 15;113(1):1-14. Epub 2007 May 22.
2. Planta Medica 1994 Jun,60(3):222-7.
3. Vaccine 1992;10(12):817-23.
4. Antibiotiki 1981 Apr;26(4):268-71.
5. Z Naturforsch [C] 1999 Jul-Aug;54(7-8):549-53.
6. Z Naturforsch [C] 1999 Jul-Aug;54(7-8):549-53.
7. Isr Med Assoc J 2002 Nov;4(11 Suppl):923-7.
8. Drugs Exp Clin Res. 1997;23(2):89-96.
9. Microbiologica. 1990 Jul;13(3):207-13.
10. J Nat Prod. 1994 May;57(5):644-7.
11. Int Immunopharmacol. 2004 Jul;4(7):975-82.
12. Planta Med. 2006 Jan;72(1):20-7.
13. J Ethnopharmacol. 2003 Feb;84(2-3):265-73.
14. Am J Chin Med. 2005;33(2):231-40.
15. J Egypt Soc Parasitol. 2007 Aug;37(2 Suppl):691-710.

Antibacterial effect of propolis is more expressed on the gram-positive (Streptococcus SP. ,Staphylococcus SP.) than on the gram-negative bacterium (Salmonella, Escherichia coli, Proteus spp., Pseudomonas aeruginosa) (1). In the antibacterial effect more ingredients of propolis are participating.

Propolis stops the multiplication of bacterium by damaging its cytoplasm, cytoplasm membrane and cellular membrane, causes the partial bacterialisis and inhibits the synthesis of proteins (2). When it’s taken with the combination of majority of antibiotics (the penicillin, ampicillin, gentamicin, penicillin G, streptomycin, tetracycline, kloksacilin, ceftriakson, chloramphenicol, neomycin, monomicin, oleandomicin, polimiksin, doksiciklin, vancomicin, cefradin, polimiksin B) antibacterical effect is stronger and period of recovery is shorter (3,4,5).

It is interesting that in case when antibiotics (the chloramphenicol, gentamicin, netilmicin, tetracycline, vancomycin, ciprofloksacin) are not functioning on some bacteria (for example Staphylococcus aureus) in combination with propolis they have the antibacterial effect (6,7,8). In cases when antibiogram shows (in vitro) that propolis doesn’t have any effect on some gram-negative bacterias (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa), in the organism (in vivo) propolis stimulates immunological system for prevention of inflammatory processes that they cause (9).

In bacterial inflammation (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pyogenes) of upper respiratory tracts or in the mouth cavity (Enterococcus faecalis, Streptococcus salivarius, Streptococcus sanguinis, Streptococcus bribe, Streptococcus mutans, Streptococcus sobrinus, Candida albicans, Lactobacillus casei) antibiotic therapy can be enhanced in the combination with propolis (10, 11, 12, 13, 14).

Considering the growing resistance (the resistance) of bacterias to antibiotics, its obvious that the revolutionary time of antibiotics is slowly comming to an end (15). Sinergistic enlargement of antibiotic effect in combination with propolis, even in cases when antibiotics alone are not functioning, points out to the promising role of propolis in antibacterial therapy. Since propolis is not toxic, it does not provoke the resistance in the organism and does not damage the normal intestinal fluorine.

Antibacterial effect on the gram-positive bacterias is not significantly different in samples of propolis from the same plant collected in different seasons. In spite of differences in the chemical structure, propolis of different fitogeografical origin is showing the similar antibacterical, antifungus and antivirus activity. Which is why propolis is pharmacologicaly valuable like natural mixture of all substances it contains (NATIVE PROPOLIS), and not like the source of new compounds against microorganisms (16,17,18).

There’s an interesting experience of one known footballer after the operation of ankle joint. Process started with high fever which clearly suggested that it is a strong inflammatory process. The inflammatory process of the ancle joint was caused by MRSA infection (golden staphylococcus , Methicillin-Resistent Staphylococcus aureus). Because that bacterium is very resistant to antibiotics, inflammation which starts lasts very long (becomes chronical) and is very difficult to cure. Thats what happend in this case. Continuation of such state would have the serious consequence on the health, and certainly on career. When he started to take large doses of native propolis (3x3 capsules daily) with the prescribed antibiotic therapy, the inflammatory process completely calmed down. Today he plays football again. 

It was scientifically established that propolis effects on next bacterias in a way that it stops their multiplication (bacteriostaticly) or it kills it (bactericidal): Bacillus larvae (19), Bacillus subtilis (20), Helicobacter pylori (21,22), MRSA (the Methicillin-Resistent Staphylococcus aureus), Mycobacterium tuberculosis (23), Staphylococcus SP, Staphylococcus aureus (9,4,20,18,24,4,25), Streptococcus SP., Streptococcus faecalis, Streptomyces (26,34), With. sobrinus, mutans, cricetus (3,27,28), Saccharomyces cerevisiae (29), Escherichia coli (9,4,24,30), Salmonella (30), Bacteroides nodosus (31,32), Klebsiella pneumoniae (17,33), Streptococcus pyogenes (6,25), Proteus vulgaris (1, 17), Pseudomonas aeruginosa (17), Streptococcus agalactiae (9), Paenibacillus larvae (35).

LITERATURE:

1. Journal of the Royal Society of Medicine 1990 Mar;83(3):159-60.
2. Planta Medica 1994 Jun,60(3):222-7.
3. Z Naturforsch [C] 1999 Jul-Aug;54(7-8):549-53.
4. Arzneimittelforschung 1993 May;43(5):607-9.
5. Microbiol Res. 2006;161(4):327-33. Epub 2006 Jan 19.
6. Journal of the Royal Society of Medicine 1990 Mar;83(3):159-60.
7. Mem Inst Oswaldo Cruz. 2005 Aug;100(5):563-6. Epub 2005 Sep 15.
8. Ophthalmic Res. 2005 Nov-Dec;37(6):328-34. Epub 2005 Aug 6.
9. Planta Medica 1994 Jun,60(3):222-7.
10. J Chemother. 2006 Apr;18(2):164-71.
11. Anaerobe. 2007 Jun-Aug;13(3-4):140-5. Epub 2007 Mar 7.
12. Anaerobe. 2002 Feb;8(1):9-15.
13. Drug Dev Ind Pharm. 2006 Feb;32(2):229-38.
14. Microbiol Res. 2005;160(2):189-95.
15. J Ethnopharmacol. 2005 Dec 1;102(3):371-6. Epub 2005 Aug 3.
16. Acta Pharm. 2003 Dec;53(4):275-85.
17. Vaccine 1992;10(12):817-23.
18. Chung Kuo Chung Yao Tsa Chih 1991 Aug;16(8):481-2, 512.
19. Apiacta 1982;17:16-20.
20. Z Naturforsch [C] 2000 Sep-Oct;55(9-10):778-84.
21. Przegl Lek 2000;57(4):191-4.
22. Phytomedicine 2001 Jan;8(1):16-23.
23. Journal of the Royal Society of Medicine Mar. 1990;83(3):159-60.
24. Z Naturforsch [C] 2001 Jan-Feb;56(1-2):82-8.
25. Antibiotiki 1981 Apr;26(4):268-71.
26. Pharmazie 1986 Feb;41(2):131-32.
27. Caries Research 1991;25(5):347-51.
28. Oral Microbiol Immunol 2002 Dec;17(6):337-43.
29. Elsevier Science publishers 1988:439-446.
30. Vopr Med Khim 1986;32(3):45-48.
31. Apimondia Publishing House, Bucharest, Romania, 1978;149-50.
32. Apiacta 1989;XXIV(3):80-81.
33. Apidologie 1991;22(2):155-62.
34. J Ethnopharmacol 2001 Feb;74(2):105-12.
35. J Invertebr Pathol. 2007 Oct 17.

There are numerous scientific proofs about the antiinflammatory effects of propolis, not just on inflammations caused by microorganisms but on aseptic inflammations which are not caused by infectious agens (burns from radiations and chemicals, autoimmune inflammations). Leading role in it has have the polyphenols from propolis. Researches discover more and more of the complexity of biochemic mechanisms which propolis starts in inflammatory processes. Its antioxidant activity is base of antiinflammatory effect which manifests itself in the prevention of oxidative stress, neutralization of free radicals and strengthened activity of antioxidant enzymes (1,2). Aside from this, propolis stimulates cells of immunological system for production of substances with the antiinflamatory effect (IL-10 etc.), but prevents creation of substances which support the inflammation (IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-12, TNF-alphas etc.) (3).

Strong antiinflammatory effect has been proved in the inflammation caused by radiation which was observed in decrease of free radicals and strengthened activity of antioxidant enzymes (4). Which is why the protection with propolis is especially significant in risky professions in medicine and industries because of the possible exposure to radiation.

In kidney inflammation (pyelonephritis) caused by bacterias (for example Escherichia coli), propolis diminishes the degree of inflammatory process because its antioxidant effect neutralizes free oxygen radicals that are damaging kidneys (5, 6).

Diabetes (diabetes mellitus type) increases the oxidative stress and accumulates free radicals in hearth that damage heart tissue. Antioxidants from propolis are reducing the consequences of oxidative stress (7).

Thanks to antiinflammatory and antioxidant activity, prevention with propolis prevents the damage of heart muscle caused by free radicals that are result of ishemical - reperfusional phenomenon* (the infarct, angioplastics, trombolisis, coronary by-pass) (8,9). Same mechanisms are used for interrupting deepening of violation of tissue after the blow (for example muscles) which is also result of ishemical - reperfusional phenomenon (10,11). The long-lasting use of propolis has no harmful effects on heart (12).

Substances from propolis are efficient in decreasing of inflammation and lung tissue damages (13).

The effect of propolis in skin transplants is favourable thanks to not just neutralizations of free radicals and increasing activity of antioxidant enzymes, but also to reduced amount of N oxides (NO) (14). N oxide is included in process of damaging tissues in inflammatory and autoimmune illnesses (15).

It is known that the oxidative tissue damages (the brain is especially sensitive) are present in the inflammatory and autoimmune illnesses (multipla scleroses, encefalomielitis). Substances out of propolis are reducing the accumulation of free radicals caused by inflammatory processes and ease clinical symptoms. The favourable effect is also because of decreased number of substances that support inflammation (NF-KAPPA B, BUT-sintetase) (16,17,18). Propolis increasingly proves itself in therapeutic potential of preventioning of neurotoxic events caused by inflammatory processes in the brain.

Considerable improvement in patients with mild to moderate asthma, who has taken propolis, can be attributed to decreasing number of substances that support inflammation and shrink respiratory tracts and enlarging antiinflammatory substances (19,3, 20,21).

It has been proved that propolis reduces the creation of cytocin which supports inflammation of colitises (22).

It is also believed that propolis prevents angiogenesis which favors inflammatory processes (23).

Antiinflammatory effect of propolis has been proved in acute and chronic inflammatory process of upper respiratory tracts, chemical violations of eye, acute and chronical arthritises and bacterial keratitis, uveitisa and rhinitis (24,25,26,27,28,29).

Ishemical - reperfusional appearance on the reduced blood flow through some organs or parts of body because of spasms or organic obstruction of arteries (ischemia), reaction of organism is huge inflow of necessary matters (the reperfusion) which causes tissue damage.

LITERATURE:

1. Drugs Exp Clin Res. 1993;19(5):197-203.
2. J Ethnopharmacol. 1996 Dec;55(1):19-25.
3. Z Naturforsch [C]. 2003 Jul-Aug;58(7-8):580-9.
4. Drugs Exp Clin Res. 1995;21(6):229-36.
5. Mol Cell Biochem. 2007 Mar;297(1-2):131-8.
6. Urol Res. 2001 Jun;29(3):190-3.
7. Clin Biochem. 2005 Feb;38(2):191-6.
8. Clin Biochem. 2004 Aug;37(8):702-5.
9. Cell Biochem Funct. 2004 Sep-Oct;22(5):287-90.
10. Scand J Plast Reconstr Surg Hand Surg. 2006;40(2):73-8.
11. Mol Cell Biochem. 2006 Nov;292(1-2):197-203.
12. J Ethnopharmacol. 2006 Apr 21;105(1-2):95-8.
13. Pulm Pharmacol Ther. 2006;19(2):90-5.
14. J Plast Reconstr Aesthet Surg. 2007;60(5):563-8.
15. J Ethnopharmacol. 2002 May;80(2-3):155-61.
16. Brain Res Mol Brain Res. 2003 Jul 23;115(2):111-20.
17. Free Radic Biol Med. 2004 Aug 1;37(3):386-94.
18. Planta Med. 2006 Aug;72(10):899-906.
19. Fundam Clin Pharmacol. 2003 Feb;17(1):93-102.
20. Int Immunopharmacol. 2006 Jul;6(7):1053-60.
21. Am J Respir Cell Mol Biol. 2006 Oct;35(4):457-65.
22. J Pharmacol Exp Ther. 2001 Dec;299(3):915-20.
23. Arch Pharm Res. 2002 Aug;25(4):500-4.
24. Rom J Virol. 1995 Jul-Dec;46(3-4):115-33.
25. Jpn J Ophthalmol. 1999 Jul-Aug;43(4):285-9.
26. Ophthalmic Res. 2005 Nov-Dec;37(6):328-34.
27. Mol Cell Biochem. 2006 Jan;281(1-2):153-61.
28. J Altern Complement Med. 2007 Sep;13(7):713-8.
29. Arch Pharm Res. 1999 Dec;22(6):554-8.

Sarić A, Balog T, Sobocanec S, Kusić B, Sverko V, Rusak G, Likić S, Bubalo D, Pinto B, Reali D, Marotti T.
Division of Molecular Medicine, Rudjer Bosković Institute, Bijenicka 54, 10000 Zagreb, Croatia.

Oxidant/antioxidant status, estrogenic/anti-estrogenic activity and gene expression profile were studied in mice fed with Cystus incanus L. (Cistaceae) reach bee pollen from location in Central Croatia’s Dalmatia coast and offshore islands. Seven phenolic compounds (out of 13 tested) in bee pollen sample were detected by high performance liquid chromatography (HPLC) analysis. Phenolics detected in C. incanus L. bee pollen belong to flavonol (pinocembrin), flavanols (quercetin, kaempferol, galangin, and isorhamnetin), flavones (chrysin) and phenylpropanoids (caffeic acid). Bee pollen as a food supplement (100mg/kgbw mixed with commercial food pellets) compared to control (commercial food pellets) modulated antioxidant enzymes (AOE) in the mice liver, brain and lysate of erythrocytes and reduced hepatic lipid peroxidation (LPO). Bee pollen induced 25% of anti-estrogenic properties while no estrogenic activity was found. Differential gene expression profile analyses after bee pollen enriched diet identify underexpressed gene Hspa9a, Tnfsf6 (liver) and down-regulated gene expression of Casp 1 and Cc121c (brain) which are important in the apoptosis pathway and chemotaxis. These results indicate that used bee pollen possess a noticable source of compounds with health protective potential and antioxidant activity.
Food Chem Toxicol. 2009 Mar;47(3):547-54. Epub 2008 Dec 16.

Research suggest that propolis may protect the organism from the harmful effects of radioactive, ultraviolet and electromagnetic radiation.

Every nuclear incidents, no matter how big, lead to radioactive pollution of the planet, food, water and air. In the long term it may increase the risk of thyroid cancer, leukaemia and bone sarcoma. Specifically, studies have showed that propolis prevents damage of chromosomes (1) and leukocyte DNA (2,3,4,5) caused by radiation. Interestingly, a study on mice which where pre-treated with propolis and afterwards irradiated by lethal dose of gamma rays, survived without any health consequences (6.7).

When using therapeutic doses of radiation, propolis suppressed inflammation of mucous membranes in the mouth (mucositis, which is a side effect of radiation) (8) and increased the effectiveness of radiation therapy in some cancers (9.10).

Exposure to sunlight raises incidence of allergies and skin cancers. Propolis has also been effective in preventing the harmful effects of solar radiation (11).

Electromagnetic radiation of mobile phones can cause an increase concentration of free radicals and oxidative stress in tissues (liver, eye, heart) and that can be prevented with some of the ingredients of propolis (12,13,14).

The protective effect of propolis from the harmful type of radiation is attributed to its capacity to eliminate free radicals, strong antioxidant abilities (1.11, 13.14, 15, 16, 17, 18) and balanced activation of the immune system (19).

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