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1: J Pharmacol Sci. 2003 Nov;93(3):307-13.

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Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle.

Paulino N, Dantas AP, Bankova V, Longhi DT, Scremin A, de Castro SL, Calixto JB.

Grupo de Pesquisa e Desenvolvimento de Biofarmacos (BIOFAR), Universidade do Sul de Santa Catarina, Tubarao, SC, Brazil.

Propolis is a bee product, which has long been used in folk medicine for the management of different diseases. In this study we evaluated the analgesic and anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7 mg. kg(-1). In the formalin test, the extract caused a significant reduction in pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/- 0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice; however, this extract was ineffective when assessed in the tail-flick and hot-plate thermal assays. The analgesic effect of Et-Blg was associated with the inhibition of inflammatory responses and not to a simple irritation of nervous terminals. In vitro, this extract inhibited the contraction of trachea smooth muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50) = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).

PMID: 14646248 [PubMed - indexed for MEDLINE]

2: Biochem Pharmacol. 2003 Dec 15;66(12):2281-9.

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Involvement of tumor suppressor protein p53 and p38 MAPK in caffeic acid phenethyl ester-induced apoptosis of C6 glioma cells.

Lee YJ, Kuo HC, Chu CY, Wang CJ, Lin WC, Tseng TH.

Department of Chemistry, National Changhua University of Education, Changhua, Taiwan, ROC.

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidant, anti-inflammation, antiviral action, and anticancer effect. Our previous studies showed that CAPE exhibited significant cytotoxicity in oral cancer cells. Herein we further investigated the cytotoxicity potential of CAPE and the mechanism of its action in C6 glioma cells. The data exhibited that C6 glioma cells underwent internucleosomal DNA fragmentation 24 hr after the treatment of CAPE (50 microM). The proportion of C6 glioma cells with hypodiploid nuclei was increased to 24% at 36 hr after the exposure. Further results showed that CAPE induced the release of cytochrome c from mitochondria into cytosol, and the activation of CPP32. CAPE application also enhanced the expression of p53, Bax, and Bak. Finally, the potential signaling components underlying CAPE induction of apoptosis were elucidated. We found that CAPE activated extracellular signal-regulated kinase (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in C6 glioma cells. More importantly, p38 kinase formed a complex with p53 after the treatment of CAPE for 0.5 hr. The expression of p53, phospho-serine 15 of p53, and Bax, and inactivate form of CPP32 was suppressed by a pretreatment of a specific p38 MAPK inhibitor, SB203580. The resultant data suggest that p38 MAPK mediated the CAPE-induced p53-dependent apoptosis in C6 glioma cells.

PMID: 14637186 [PubMed - indexed for MEDLINE]

3: Life Sci. 2003 Jul 11;73(8):1027-35.

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Effect of propolis on human cartilage and chondrocytes.

Cardile V, Panico A, Gentile B, Borrelli F, Russo A.

Department of Physiological Sciences, University of Catania, v.le A. Doria 6, 95125, Catania, Italy.

Propolis, a natural product derived from plant resins collected by the honeybees, has been used for thousands of years in folk medicine for several purposes. The extract that contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid, possesses several biological activities such as anti-inflammatory, immunostimulatory, anti-viral and anti-bacterial. In this study, we assay the effects of propolis extract on the production of key molecules released during chronic inflammatory events as nitric oxide (NO) and glycosaminoglycans (GAGs) in cultures of human cartilaginous tissues and chondrocytes, stimulated with interleukin-1beta (IL-1beta). We observed that this natural compound and its active principle, caffeic acid phenethyl ester (CAPE), were able to contrast the harmful effects of IL-1beta.Our data clearly demonstrated the protective action of propolis in cartilage alteration, that appears greater than that elicited by indomethacin, commonly employed in joint diseases.

PMID: 12818355 [PubMed - indexed for MEDLINE]

4: Arch Pharm Res. 2002 Dec;25(6):895-902.

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Activation of murine macrophage cell line RAW 264.7 by Korean propolis.

Han S, Sung KH, Yim D, Lee S, Cho K, Lee CK, Ha NJ, Kim K.

Department of Pharmacy, Sahmyook University, 26-21 Gonglung-Dong, Seoul, 139-742 South Korea.

Monocytes and macrophages play a major role in defense mechanism of the host response to tumor, in part through the secretion of several potent products and macrophage cytokines. Monocytes and tissue macrophages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and tumor necrosis factor (TNF). Recent studies emphasizes that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. In this study, our work is directed toward studying the in vitro effects of Korean propolis on the ability to induce cellular and secretory responses in murine macrophage cell line, RAW 264.7. It was found that Water Extract of Korean Propolis (WEP) could activate macrophages by producing cytokines. The production of the macrophage cytokines, IL-1 and TNF-alpha, by RAW 264.7 treated with WEP was examined from 2.5 microg/ml up to 25 microg/ml with dose dependent manner. Nitric oxide (NO) production was also increased when cells were exposed to combination of LPS and WEP from 2.5 microg/ml up to 25 microg/ml. At high dose of WEP (50 to 100 microg/ml) used to prescribe for anti-inflammatory and analgesic medicine showed inhibition of NO production in LPS-stimulated macrophage. Besides cytokine production, NO release, surface molecule expression and cell morphologic antigen expression were increased in response to the stimulation by WEP. These results suggested WEP may function through macrophage activation.

PMID: 12510845 [PubMed - indexed for MEDLINE]

5: Fitoterapia. 2002 Nov;73 Suppl 1:S30-7.

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The role of the phenethyl ester of caffeic acid (CAPE) in the inhibition of rat lung cyclooxygenase activity by propolis.

Rossi A, Longo R, Russo A, Borrelli F, Sautebin L.

Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.

In this study we investigated the effect of an ethanolic extract of propolis, with and without CAPE, and some of its components on cyclooxygenase (COX) activity. Propolis (0.00003-0.03%) significantly and concentration-dependently inhibited COX activity from lung homogenate of saline- or LPS-treated rats. Same results were obtained with CAPE (0.1-100 microM). COX activity from lung homogenate of saline- or LPS-treated rats was also inhibited by galangin (0.1-100 microM), although the inhibition induced by the lowest concentration was not significant. Caffeic, ferulic, cinnamic and chlorogenic acids and pinocembrin, (0.1-100 microM) did not affect COX activity. The inhibition curves showed that CAPE and propolis were equipotent inhibitors, whereas galangin was significantly (P<0.001) less potent than propolis and CAPE. In order to better investigate the role of CAPE, we tested the action of an ethanolic extract of propolis (0.00003-0.03%) without CAPE. This extract significantly and concentration-dependently inhibited COX activity from lung homogenate of saline- or LPS-treated rats, however, it resulted to be approximately 10 times less potent than the extract containing CAPE. The analysis of the inhibition curves of the extract with and without CAPE showed a significant (P<0.001) difference. These results suggest that both CAPE and galangin contribute to the overall activity of propolis, CAPE being more effective.

PMID: 12495707 [PubMed - indexed for MEDLINE]

6: 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]

7: Arch Pharm Res. 1999 Dec;22(6):554-8.

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Suppressive effects of propolis in rat adjuvant arthritis.

Park EH, Kahng JH.

College of Pharmacy, Sookmyung Women's University, Seoul, Korea.

The effects of ethanolic extract (EEP) of propolis on chronic inflammation were evaluated using rat adjuvant arthritis. In the chronic inflammatory animal model, the arthritis index was suppressed by EEP treatments (50 mg/kg/day and 100 mg/kg/day, p.o.). Moreover, physical weakness, induced by the chronic disease state, was dose-dependently improved in the EEP-treated groups. Its analgesic effect, assessed using the tail-flick test, was comparable to prednisolone (2.5 mg/kg/day, p.o.) and acetyl salicylic acid (100 mg/kg/day, p.o.). In carrageenan rat hind paw edema, which was conducted to test the effects of subfractions of EEP, the petroleum ether sub-fraction (100 mg/kg, p.o.) showed an inhibitory effect on the paw edema whereas EEP (200 mg/kg, p.o.) showed a significant anti-inflammatory effect at 3 and 4 hrs after carrageenan injection. From these results, we conclude that the ethanolic extract of propolis had a profound anti-inflammatory effects on both chronic and acute inflammations.

PMID: 10615859 [PubMed - indexed for MEDLINE]

8: Arzneimittelforschung. 1999 Aug;49(8):705-7.

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Mouse ear edema modulation by different propolis ethanol extracts.

Menezes H, Alvarez JM, Almeida E.

Department of Biochemistry and Microbiology, Universidade Estadual Paulista, Rio Claro, Sao Paulo State, Brazil.

The anti-inflammatory activity of 14 commercial ethanol extracts of propolis were evaluated, using a mouse ear inflammation model induced by arachidonic acid. Indometacin was also assayed as standard anti-inflammatory agent. Different activities were observed and discussed. This model could be used to assess the anti-inflammatory quality of propolis extracts and facilitate their posological usage on skin edema resulting from wounds.

PMID: 10483518 [PubMed - indexed for MEDLINE]

9: Jpn J Ophthalmol. 1999 Jul-Aug;43(4):285-9.

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Effect of propolis on endotoxin-induced uveitis in rabbits.

Ozturk F, Kurt E, Inan UU, Emiroglu L, Ilker SS, Sobaci G.

Department of Ophthalmology, Celal Bayar University Faculty of Medicine, Manisa, Turkey.

PURPOSE: To test the anti-inflammatory effect of propolis, a natural bee-produced compound, and compare it with corticosteroids for the treatment of endotoxin-induced uveitis (EIU). METHODS: EIU was produced in all rabbits by unilateral intravitreal injection of 2,000 ng Salmonella typhimurium endotoxin. The animals were then divided randomly into three groups as follows: group A received no treatment (control); group B received methylprednisolone (5 mg/0.1 mL) (positive control); and group C received propolis (5 mg/0.16 mL) by anterior sub-Tenon injection at the time of uveitis induction and at 4 and 8 hours after induction. Inflammation was evaluated by clinical manifestations and by measuring the protein concentration and inflammatory cell content of the aqueous humor. RESULTS: The clinical grade, cell count, and protein levels in the aqueous humor were: control group (6.0 +/- 0.8, 2,519 +/- 470 cells/microL, 32.9 +/- 2.4 mg/mL); methylprednisolone group (1.8 +/- 0.7, 572 +/- 137 cells/microL, 15.2 +/- 1.8 mg/mL); and propolis group (2.3 +/- 0.5, 503 +/- 124 cells/microL, 13.8 +/- 1.5 mg/mL). Statistically significant differences were recorded in the treatment groups when compared to the control group (P < .001). The effects of methylprednisolone and propolis on EIU were similar (P > .05). CONCLUSIONS: Propolis showed significant anti-inflammatory effects on EIU in rabbits. The mechanism of its action warrants further investigation.

PMID: 10482473 [PubMed - indexed for MEDLINE]

10: Zhongguo Yao Li Xue Bao. 1997 May;18(3):274-6.

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Antipsoriatic, anti-inflammatory, and analgesic effects of an extract of red propolis.

Ledon N, Casaco A, Gonzalez R, Merino N, Gonzalez A, Tolon Z.

Department of Pharmacology, National Center for Scientific Research, Havana, Cuba.

AIM: To study the antipsoriatic, anti-inflammatory, and analgesic effects of ethanolic extract of red propolis. METHODS AND RESULTS: This extract induced the formation of granular layer in the mouse tail test used as a model of psoriasis. Propolis 50 i.g. showed anti-inflammatory activity in the cotton-pellet granuloma assay in rats, in croton oil-induced edema in mice at a dose of 25% (2.5 microL), and in the peritoneal capillary permeability test in mice at a dose of 10 The extract (25 i.g.) showed analgesic effect in the model of acetic acid-induced writhings, whereas 40 was effective in the hot plate test in mice. CONCLUSION: Anti-inflammatory, analgesic, and antipsoriatric properties of Cuban red propolis were evident.

PMID: 10072950 [PubMed - indexed for MEDLINE]

11: J Pharm Pharmacol. 1998 Oct;50(10):1187-93.

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Anti-hyperalgesic effect of an ethanolic extract of propolis in mice and rats.

de Campos RO, Paulino N, da Silva CH, Scremin A, Calixto JB.

Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, Brazil.

Propolis, or bee glue, which contains a complex mixture of secondary metabolites, has long been used in many countries for the management of several diseases. The purpose of this study was to evaluate, by means of several pharmacological models, the anti-hyperalgesic effect of propolis collected in the south of Brazil. The abdominal constrictions induced in mice by intraperitoneal injection of acetic acid (0.6%), kaolin (50 mg kg-1) or zymosan (40 mg kg-1) were inhibited to different extents by an extract of propolis (1-60 mg kg-1) administered intraperitoneally 30 min earlier; mean ID50 (concentrations resulting in 50% inhibition) values were 2.7, 10.8 and 10.7 mg kg-1, respectively, and maximum inhibition was 58 +/- 5, 57 +/- 10 and 51 +/- 5%, respectively. Given orally (25-200 mg kg-1, 1h previously) propolis also inhibited the abdominal constrictions induced by acetic acid (maximum inhibition 43 +/- 5%). When injected intraperitoneally (3-60 mg kg-1, 30 min previously), propolis attenuated both the neurogenic (first phase) and inflammatory (second phase) pain responses and paw oedema caused by intraplantar injection of formalin (2.5%); maximum inhibition was 32 +/- 5, 43 +/- 6 and 19 +/- 2%, respectively. Oral administration of propolis (25-200 mg kg-1, 1 h previously) inhibited both phases and reduced the oedema formation associated with the second phase of the formalin test (maximum inhibition 22 +/- 5, 33 +/- 6 and 26 +/- 3%) and extract of propolis (3-30 mg kg-1 i.p. or 25-100 mg kg-1 p.o., respectively 30 min and 1 h previously) significantly inhibited capsaicin-induced pain with maximum inhibition of 39 +/- 8 and 41 +/- 8%, respectively. When assessed in the Randall-Sellito test of pain, the extract of propolis (3-30 mg kg-1, i.p., 30 min previously) significantly reversed the hyperalgesia induced by intraplantar injection of bradykinin (3 nmol per paw) in rats (P < 0.01). In contrast with morphine the extract of propolis (< or = 100 mg kg-1, 30 min previously) was ineffective when assessed in the tail-flick and hot-plate thermal assays. Naloxone (5 mg kg-1 i.p.) reversed (P < 0.01) the effect of morphine (5 mg kg-1 s.c.) by 70 and 94% respectively in the first and second phases of the formalin test, but did not interfere with the analgesic effect of propolis (10 mg kg-1 i.p., 30 min previously). These results show that ethanolic extract of propolis, given systemically, has significant anti-hyperalgesic action when assessed in chemical, but not thermal, models of nociception in mice and rats. Its analgesic action seems to be unrelated to release or activation of the opioid system.

PMID: 9821669 [PubMed - indexed for MEDLINE]

12: Prostaglandins Leukot Essent Fatty Acids. 1996 Dec;55(6):441-9.

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The effect of propolis and its components on eicosanoid production during the inflammatory response.

Mirzoeva OK, Calder PC.

Department of Biochemistry, University of Oxford, UK.

To investigate the possible mechanism of the therapeutic action of propolis, we studied: (a) the effect of propolis, its components, caffeic acid phenethyl ester (CAPE), caffeic acid (CA), quercetin and naringenin, as well as the synthetic compounds indomethacin (IM) and nordihydroguaiaretic acid (NDGA), and a novel lipoxygenase inhibitor N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)isourea (DCHCU) on eicosanoid production by mouse peritoneal macrophages in vitro; (b) the effect of IM, NDGA, CA, CAPE, DCHCU and propolis on eicosanoid production during acute inflammation in vivo; and (c) the ex vivo and in vivo effect of dietary propolis on arachidonic acid metabolism. The ethanol extract of propolis suppressed prostaglandin and leukotriene generation by murine peritoneal macrophages in vitro and during zymosan-induced acute peritoneal inflammation in vivo. Dietary propolis significantly suppressed the lipoxygenase pathway of arachidonic acid metabolism during inflammation in vivo. CAPE was the most potent modulator of the arachidonic acid cascade among the propolis components examined.

PMID: 9014224 [PubMed - indexed for MEDLINE]

13: Mol Med Today. 1996 Jul;2(7):271.

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Bee-glue reveals anti-inflammatory properties plus...

Jack DB.

Publication Types:


PMID: 8796903 [PubMed - indexed for MEDLINE]

14: 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]

15: 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]

16: 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]

17: Zhonghua Kou Qiang Ke Za Zhi. 1986 Jul;21(4):209-11.

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[Ulcerative lesions of the oral mucosa treated by propolis]

[Article in Chinese]

Shen SL.

PMID: 3471404 [PubMed - indexed for MEDLINE]

18: Arzneimittelforschung. 1978;28(2):291-2.

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Biological properties and clinical application of propolis. X. Preliminary pharmacological evaluation of ethanol extract of propolis (EEP).

Kleinrok Z, Borzecki Z, Scheller S, Matuga W.

A study consisting of an examination of the acute toxicity of ethanol extract of propolis (EEP) in mice, its effect on spontaneous movement in mice and rats, its analgesic properties and its influence on body temperature in mice was conducted. Also examined was the activity of EEP on animals under the influence of narcotics and spontaneous movement under the influence of amphetamine, its effects on blood pressure and respiration in rats. The results of these examinations indicate that EEP injected i.p. has a weak general effect on the experimental animals.

PMID: 580395 [PubMed - indexed for MEDLINE]