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1: Int Immunopharmacol. 2005 Feb;5(2):359-68.

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Effects of Brazilian and Bulgarian propolis on bactericidal activity of macrophages against Salmonella Typhimurium.

Orsi RO, Sforcin JM, Funari SR, Bankova V.

Department of Production and Animal Exploration-School of Veterinary Medicine and Animal Husbandry-UNESP, 18618-000 Botucatu, SP, Brazil.

Propolis has been used in folk medicine since ancient times due to its many biological properties, such as antimicrobial, antiinflammatory, antioxidant, immunomodulatory activities, among others. Macrophages play an important role in the early phase of Salmonella infection. In this work, macrophages were prestimulated with Brazilian or Bulgarian propolis and subsequently challenged with Salmonella Typhimurium at different macrophage/bacteria ratio. After 60 min of incubation, cells were harvested with Triton-X to lyse the macrophages. To assess the bactericidal activity, the number of colony-forming units (CFU) of S. typhimurium was determined by plating 0.1 mL in Mueller Hinton agar. After 24 h, CFU were counted, and the percentage of bactericidal activity was obtained. Propolis from Brazil and Bulgaria enhanced the bactericidal activity of macrophages, depending on its concentration. Brazilian propolis seemed to be more efficient than that from Bulgaria, because of their different chemical composition. In Bulgaria, bees collect the material mainly from the bud exudate of poplar trees, while in Brazil, Baccharis dracunculifolia DC. was shown to be the main propolis source. Our data also showed that the increased bactericidal activity of macrophages involved the participation of oxygen (H(2)O(2)) and nitrogen (NO) intermediate metabolites.

PMID: 15652765 [PubMed - indexed for MEDLINE]

2: Biol Pharm Bull. 2003 Apr;26(4):487-91.

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Caffeic acid phenethyl ester (CAPE) analogues: potent nitric oxide inhibitors from the Netherlands propolis.

Nagaoka T, Banskota AH, Tezuka Y, Midorikawa K, Matsushige K, Kadota S.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.

The MeOH and water extracts of the Netherlands propolis were tested for their inhibitory activity toward nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage-like J774.1 cells. Both of the extract possessed significant NO inhibitory activity with IC(50) values of 23.8 and 51.5 microg/ml, respectively. Then 13 phenolic compounds obtained from the MeOH extract showing stronger NO inhibition were examined on their NO inhibitory activities. Caffeic acid phenethyl ester (CAPE) analogues, i.e., benzyl caffeate, CAPE and cinnamyl caffeate, possessed most potent NO inhibitory activities with IC(50) values of 13.8, 7.64 and 9.53 microM, respectively, which were two- to four-fold stronger than the positive control N(G)-monomethyl-L-arginine (L-NMMA; IC(50), 32.9 microM). Further study on the synthetic analogues of CAPE revealed that both of 3-phenylpropyl caffeate (18; IC(50), 7.34 microM) and 4-phenylbutyl caffeate (19; IC(50), 6.77 microM) possessed stronger NO inhibitory activity than CAPE (10) and that elongation of alkyl side chain of alcoholic parts of caffeic acid esters enhance the NO inhibitory activity. In addition, it was found that CAPE analogues having longer carbon chain (>C(5)) in alcoholic part showed toxic effects toward J774.1 cells. This NO inhibitory effect may directly correlate with antiinflammatory properties of the Netherlands propolis.

PMID: 12673030 [PubMed - indexed for MEDLINE]

3: Fitoterapia. 2002 Nov;73 Suppl 1:S21-9.

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Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin.

Russo A, Longo R, Vanella A.

Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, V.le A. Doria 6, 95125, Catania, Italy.

Propolis, a natural product produced by the honeybee, has been used for thousands of years in folk medicine for several purposes. The extract contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid. It possesses several biological activities such as antiinflammatory, immunostimulatory, antiviral and antibacterial. The exact mode of physiological or biochemical mechanisms responsible for the medical effects, however, is yet to be determined. In this work, we have investigated the antioxidant activity of a propolis extract deprived of caffeic acid phenethyl ester (CAPE). In addition, the activity of CAPE and galangin was also examined. Propolis extract (with and without CAPE) and its active components showed a dose-dependent free radical scavenging effect, a significant inhibition of xanthine oxidase activity, and an antilipoperoxidative capacity. Propolis extract with CAPE was more active than propolis extract without CAPE. CAPE, used alone, exhibited a strong antioxidant activity, higher than galangin. The experimental evidence, therefore, suggests that CAPE plays an important role in the antioxidant activity of propolis.

PMID: 12495706 [PubMed - indexed for MEDLINE]

4: Curr Eye Res. 2001 Oct;23(4):291-7.

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Effect of caffeic acid phenethyl ester on corneal neovascularization in rats.

Totan Y, Aydin E, Cekic O, Cihan Dagloglu M, Borazan M, Daglioglu K, Gultek A.

Department of Ophthalmology, Inonu University School of Medicine, Malatya, Turkey.

PURPOSE: Caffeic acid phenethyl ester (CAPE), a biologically active component of propolis from honeybee hives, has potent antiinflammatory and antioxidant properties. We aimed to evaluate the ability of topically applied CAPE in comparison with known steroidal (dexamethasone sodium phosphate) and nonsteroidal (indomethacin) topical agents to reduce corneal neovascularization (CNV) induced by silver nitrate cauterization in rats. METHODS: Following silver nitrate cauterization on both eyes, male rats were randomly assigned to the study and control groups, each consisting of ten rats. The inhibitory effects of the test drugs against a placebo (isotonic saline) on CNV were tested and compared to each other using a previously described method in which extent of neovascularization and burn stimulus intensity were scored by a masked examiner. Briefly, burn stimulus intensity was scored from 0 to +3 according to the height of blister from corneal surface, and extent of neovascularization was recorded from 0 to +6 according to the distance from limbus to the end point of CNV toward the central corneal burn. Results. The mean burn stimulus score were not different among the groups (P = 0.807). Percent inhibition of CNV compared to the placebo control and its significance were 31.5 %, P = 0.011 for indomethacin; 56 %, P < 0.001 for dexamethasone; and 52 %, P < 0.001 for CAPE. Dexamethasone was significantly (P < 0.05) more effective than indomethacin in inhibition of neovascular growth. CAPE was found to be superior (P < 0.05) to indomethacin and almost as effective as (P > 0.05) dexamethasone in reducing CNV. Conclusion. Topically applied CAPE was demonstrated to have an inhibitory effect, comparable to that of topical dexamethasone, on CNV in this rat model. Antiinflammatory and antioxidant properties of CAPE may contribute to its suppression on CNV.

PMID: 11852431 [PubMed - indexed for MEDLINE]

5: Phytother Res. 2001 Nov;15(7):561-71.

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Recent progress in pharmacological research of propolis.

Banskota AH, Tezuka Y, Kadota S.

Department of Natural Products Chemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630-Sugitani, Toyama 930-0194, Japan.

Propolis is a resinous hive product collected by honeybees from various plant sources. It is a popular folk medicine possessing a broad spectrum of biological activities. It has also been used as a health drink in various Asian, European and American countries. Several groups of researchers have focused their attention on the biological activity of propolis and its active principles. Many scientific articles are published every year in different international journals related to the pharmacological properties of propolis. This review article compiles recent findings (since 1995) on the pharmacological properties of propolis focusing on its antihepatotoxic, antitumour, antioxidative, antimicrobial and antiinflammatory properties. The possible mechanism of action of propolis as well as the active compounds are discussed.
Copyright 2001 John Wiley & Sons, Ltd.

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PMID: 11746834 [PubMed - indexed for MEDLINE]

6: Arzneimittelforschung. 2000 Apr;50(4):373-9.

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Antiapoptotic effects of propolis extract and propol on human macrophages exposed to minimally modified low density lipoprotein.

Claus R, Kinscherf R, Gehrke C, Bonaterra G, Basnet P, Metz J, Deigner HP.

Institute of Pharmaceutical Chemistry, University of Heidelberg, Germany.

An aqueous extract of propolis and the phenolic component of propolis, propol, were assayed for antioxidative and antiapoptotic properties. Both additions inhibited Cu(2+)-initiated low density lipoprotein (LDL) oxidation as characterized by a reduction of the lag time, reduced the increase of relative electrophoretic mobility during oxidation and markedly diminished apoptosis of human macrophages exposed to minimally modified (mmLDL). Moreover, aqueous propolis extract and propol blocked the mmLDL-induced decrease of glutathione (GSH) and the activation of the transcription factor NF-kappa B in these cells. The potent phenolic antioxidant propol thus expands the capability of cells to neutralize oxidative stress and to prevent apoptosis and is therefore suggested to significantly contribute to the antiinflammatory and antioxidative effects of propolis.

PMID: 10800636 [PubMed - indexed for MEDLINE]

7: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9090-5.

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Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB.

Department of Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory, and immunomodulatory properties. The molecular basis for these diverse properties is not known. Since the role of the nuclear factor NF-kappa B in these responses has been documented, we examined the effect of CAPE on this transcription factor. Our results show that the activation of NF-kappa B by tumor necrosis factor (TNF) is completely blocked by CAPE in a dose- and time-dependent manner. Besides TNF, CAPE also inhibited NF-kappa B activation induced by other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, and okadaic acid. Since the reducing agents reversed the inhibitory effect of CAPE, it suggests the role of critical sulfhydryl groups in NF-kappa B activation. CAPE prevented the translocation of the p65 subunit of NF-kappa B to the nucleus and had no significant effect on TNF-induced I kappa B alpha degradation, but did delay I kappa B alpha resynthesis. The effect of CAPE on inhibition of NF-kappa B binding to the DNA was specific, in as much as binding of other transcription factors including AP-1, Oct-1, and TFIID to their DNA were not affected. When various synthetic structural analogues of CAPE were examined, it was found that a bicyclic, rotationally constrained, 5,6-dihydroxy form was superactive, whereas 6,7-dihydroxy variant was least active. Thus, overall our results demonstrate that CAPE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities.

PMID: 8799159 [PubMed - indexed for MEDLINE]

8: Orv Hetil. 1996 Jun 23;137(25):1365-70.

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Comment in:

       Orv Hetil. 1996 Jun 23;137(25):1363-4.

[Local treatment of rheumatic diseases with propolis compounds]

[Article in Hungarian]

Siro B, Szelekovszky S, Lakatos B, Mady G, Szathmari E, Karanyi Z.

Debreceni Orvostudomanyi Egyetem I. Belgyogyaszati Klinika.

The authors conducted a single blind, placebo controlled local therapy trial on a total of 190 patients involving the use of materials (i) topically and (ii) by iontophoresis for pain and/or inflammation of the organs of movement. The materials used comprised of the following: (i) purified propolis and propolis saturated with antiinflammatory trace metal elements and (ii) propolis saturated with trace metal elements and poplar bud ointment saturated with trace metal elements also. Both methods of application using all the three preparations significantly improved symptoms. The preparations saturated with metallic ions were more effective. The mild effect of the placebo treatment is explained by the treatment procedure itself.
Side effects were not observed.

Publication Types:

       Clinical Trial

       Controlled Clinical Trial

PMID: 8757085 [PubMed - indexed for MEDLINE]

9: Drugs Exp Clin Res. 1995;21(6):229-36.

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The use of aqueous propolis extract against radiation-induced damage.

El-Ghazaly MA, Khayyal MT.

Department of Drug Radiation Research, National Centre for Radiation Research and Technology, Nasr City, Cairo, Egypt.

Whole body exposure to gamma radiation has been experimentally shown to exaggerate inflammatory responses and to enhance the release of mediators. A thirteen per cent aqueous extract of propolis (bee glue) was previously shown to have potent antiinflammatory activity. The present study was carried out to show whether the extract could influence the exaggerated inflammatory response in irradiated animals. Rats were exposed to acute (2 and 6 Gy) & fractionated (1 Gy/week) doses of gamma ionizing radiation. Treatment with the aqueous extract orally (5 ml/kg) before and after radiation exposure markedly reduced the exaggerated paw oedema response to carrageenan. In the acute phase of adjuvant-induced arthritis, exposure to ionizing radiation caused an increase in serum acid phosphatase level. Malondialdehyde concentration in plasma and superoxide dismutase activity in blood significantly increased. Treatment with aqueous propolis extract prior to irradiation reduced malondialdehyde concentration in plasma and normalized the serum acid phosphatase level. The extract stimulated the release of superoxide dismutase enzyme. Aqueous propolis extract could possibly be of therapeutic value in protecting against inflammatory responses induced by gamma radiation.

PMID: 8907698 [PubMed - indexed for MEDLINE]

10: Z Naturforsch [C]. 1994 Jan-Feb;49(1-2):39-43.

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Biochemical activities of propolis-extracts. III. Inhibition of dihydrofolate reductase.

Strehl E, Volpert R, Elstner EF.

Institut fur Botanik und Mikrobiologie, Biochemisches Labor, Technische Universitat Munchen.

Ethanolic and aqueous extracts of the natural compound PROPOLIS indicate substantial antiinflammatory functions as well as antibiotic activities in vitro and in vivo. The exact mode of physiological or biochemical mechanisms responsible for the medical effects, however, is all but clear. The standardization on the basis of quantitative determination of prominent components of these extracts have been substituted recently by simple biochemical model reactions including photodynamic properties. In this communication we report on the inhibitory activity of an aqueous extract of propolis on the enzyme dihydrofolate reductase. This activity may at least partially be due to the content of caffeic acid, as revealed by HPLC chromatography and comparative activity tests of representative ingredients of the propolis extract. This result may explain some of the protective functions of propolis, similar to those shown for several "non-steroidal antiinflammatory drugs", NSAIDs.

PMID: 8148008 [PubMed - indexed for MEDLINE]

11: Z Naturforsch [C]. 1993 Nov-Dec;48(11-12):858-62.

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Biochemical activities of propolis extracts. II. Photodynamic activities.

Volpert R, Elstner EF.

Institut fur Botanik und Mikrobiologie, Biochemisches Labor, Technische Universitat Munchen, Bundesrepublik Deutschland.

Ethanolic and aqueous extracts of the "bee glue" Propolis exhibit antioxidative properties and are used as antiinflammatory drugs in folk medicine. In order to standardize the principle activities of prominent components of these extracts, simple biochemical tests have been introduced in the preceding paper. These activity tests prove the high antioxidative and inhibitory capacities of aqueous and ethanolic extracts of propolis in vitro. In the present communication we report on experiments documenting photodynamic quenching properties of these extracts. Using riboflavin, rose bengal or hematoporphyrin as photoactivators and ketomethylthiobutyric acid or crocin as indicators, the protective functions of propolis preparations can be demonstrated. The results indicate that the aqueous extracts are more active than the corresponding ethanolic preparation.

PMID: 8297423 [PubMed - indexed for MEDLINE]

12: Z Naturforsch [C]. 1993 Nov-Dec;48(11-12):851-7.

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Biochemical activities of propolis extracts. I. Standardization and antioxidative properties of ethanolic and aqueous derivatives.

Volpert R, Elstner EF.

Institut fur Botanik und Mikrobiologie, Biochemisches Labor, Technische Universitat Munchen, Bundesrepublik Deutschland.

Ethanolic extracts of Propolis are used as antiinflammatory and wound healing drugs since ancient times. In order to facilitate a comparison of different extracts, the standardization on the basis of quantitative determination of prominent components of these extracts has been substituted for simple biochemical "activity" tests. One of these activity tests bases on the inhibition of peroxidase-catalyzed oxidation of indole acetic acid indicating the presence of a defined mixture of monophenolic and diphenolic compounds. Other tests (diaphorase-catalyzed reductions and xanthine oxidase-catalyzed oxidations) demonstrate significant radical scavenging properties. Water-soluble extracts of propolis exhibit higher antioxidative and inhibitory activities as compared to the ethanolic extract.

PMID: 8297422 [PubMed - indexed for MEDLINE]

13: Cancer Res. 1993 Mar 15;53(6):1255-61.

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Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester.

Frenkel K, Wei H, Bhimani R, Ye J, Zadunaisky JA, Huang MT, Ferraro T, Conney AH, Grunberger D.

Department of Environmental Medicine, New York University Medical Center, New York 10016-6451.

Caffeic acid phenethyl ester (CAPE) was isolated from propolis (a product of honeybee hives) that has been used in folk medicine as a potent antiinflammatory agent. CAPE is cytotoxic to tumor and virally transformed but not to normal cells. Our main goal was to establish whether CAPE inhibits the tumor promoter (12-O-tetradecanoylphorbol-13-acetate)-induced processes associated with carcinogenesis. Topical treatment of SENCAR mice with very low doses (0.1-6.5 nmol/topical treatment) of CAPE strongly inhibits the following 12-O-tetradecanoylphorbol-13-acetate-mediated oxidative processes that are considered essential for tumor promotion: (a) polymorphonuclear leukocyte infiltration into mouse skin and ears, as quantified by myeloperoxidase activity; (b) hydrogen peroxide (H2O2) production; and (c) formation of oxidized bases in epidermal DNA, as measured by 5-hydroxymethyluracil and 8-hydroxylguanine. A 0.5-nmol dose of CAPE suppresses the oxidative burst of human polymorphonuclear leukocytes by 50%. At higher doses (1-10 mumol), CAPE inhibits edema and ornithine decarboxylase induction in CD-1 and SENCAR mice. Interestingly, we discovered that 12-O-tetradecanoylphorbol-13-acetate-induced H2O2 production in bovine lenses also is inhibited by CAPE. Cumulatively, these findings point to CAPE as being a potent chemopreventive agent, which may be useful in combating diseases with strong inflammatory and/or oxidative stress components, i.e., various types of cancer and possibly cataract development.

PMID: 7680281 [PubMed - indexed for MEDLINE]

14: Drugs Exp Clin Res. 1993;19(5):197-203.

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Mechanisms involved in the antiinflammatory effect of propolis extract.

Khayyal MT, el-Ghazaly MA, el-Khatib AS.

Department of Pharmacology, Faculty of Pharmacy, Cairo University, Egypt.

Propolis is a natural product produced by the honey bee. The extract contains amino acids, flavanoids, terpenes and cinnamic acid derivatives. In various in vitro models propolis extract was shown to inhibit platelet aggregation and to inhibit eicosanoid synthesis, suggesting that it might have potent antiinflammatory properties. A 13% aqueous extract was tested orally in three dose levels (1, 5 and 10 ml/kg) on the carrageenan rat paw oedema model and on adjuvant-induced arthritis in rats. In both models, the extract showed potent dose-related antiinflammatory activity, which compared well with that of diclofenac (as a reference standard). The extract was then tested on an isolated sensitized guinea pig lung preparation to study its effect on the release of prostaglandins, leukotrienes and histamine. It is concluded that propolis extract has potent antiinflammatory properties in vivo. Its activity can be well correlated with its effects on the release of various mediators of inflammation.

PMID: 7513636 [PubMed - indexed for MEDLINE]

15: J Ethnopharmacol. 1991 Oct;35(1):77-82.

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Antibacterial, antifungal, antiamoebic, antiinflammatory and antipyretic studies on propolis bee products.

Dobrowolski JW, Vohora SB, Sharma K, Shah SA, Naqvi SA, Dandiya PC.

Institute of Management and Protection of Environment, Krakow, Poland.

PMID: 1753797 [PubMed - indexed for MEDLINE]

16: Rev Chir Oncol Radiol O R L Oftalmol Stomatol Ser Stomatol. 1989 Apr-Jun;36(2):91-8.

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[Apiphytotherapeutic original preparations in the treatment of chronic marginal parodontopathies. A clinical and microbiological study]

[Article in Romanian]

Gafar M, Dumitriu H, Dumitriu S, Guti L.

The paper presents results obtained by the treatment of chronic marginal parodontopathies with natural products of apiarian derivatives and vegetal extracts. These are original preparations such as Proparodont, sage extracts, watercress extracts, etc., by comparison with other similar existing products, and with zinc chloride. The clinical study evaluated the "inflammation status of the marginal prodontium" on the basis of variations in the PMA index. The microbiological study has established the bacteriostatic and the bactericidal activities of the products employed. The results obtained stress the high antimicrobial activity of the original products called Proparodont, and stress its antimycotic effects, especially against Candida albicans. The blackwort (Symphytum off.) extracts have a good repair effect, especially after surgical procedures. The complex original products based on propolis and vegetal extracts are indicated in the treatment of inflammatory lesions of the gingivo-parodontal tissues, and of the buccal mucosa. They also have antimicrobial effects, as well as antimycotic, antiinflammatory and antiscar effects. They de not have side effects which are characteristic for other medicinal drugs employed in the treatment of chronic marginal parodontopathies.

PMID: 2535077 [PubMed - indexed for MEDLINE]

17: Vestn Khir Im I I Grek. 1985 May;134(5):119-22.

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[Use of propolis in the treatment of local suppurative infection]

[Article in Russian]

Tsarev NI, Petrik EV, Aleksandrova VI.

Experience with the treatment of 460 patients with panaritium, abscesses, phlegmons, infectious wounds have shown that propolis is an expedient remedy (in additional to the the routine treatment). They have shown the stimulating, antiinflammatory and anti-microbial action of propolis.

PMID: 4035908 [PubMed - indexed for MEDLINE]

18: Agents Actions Suppl. 1982;10:129-34.

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Influence of flavonoids on capillary permeability, carrageenin edema and histamine and PGE2 spasms.

Metzner J, Bekemeier H, Weber FG.

Bioflavonoids from propolis and 6-halogenated flavanones were tested with respect to their effects on increased capillary permeability and to their antiinflammatory and antispasmodic actions, respectively. The 5,7,8-trimethoxy- and 6-fluorflavanone seem to be the best compounds tested.

PMID: 6956213 [PubMed - indexed for MEDLINE]