PROPOLEOS INMUNOMODULADOR / IMMUNOMODULATORY
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| 1: Planta Med. 2006 Jan;72(1):20-7. |
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Direct and Indirect Mechanism(s)
of Antitumour Activity of Propolis and its Polyphenolic Compounds.
Orsolic N, Saranovic AB,
Basic I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Zagreb, Croatia.
The immunomodulatory actions of a water-soluble derivative of propolis (WSDP)
and two components of propolis, caffeic acid (CA) and caffeic acid phenethyl
ester (CAPE) were investigated. Oral administration (50 mg/kg) of WSDP, CA,
and CAPE enhanced the weight and cellularity of the spleen (p < 0.05, p
< 0.01) of treated mice. The response of spleen cells to polyclonal mitogens
(PHA, Con A, PWM) was also increased in mice treated with WSDP as compared
to control (p < 0.01); in contrast, the response of spleen cells of mice
treated with CA were significantly suppressed (p < 0.001). The colony forming
ability of HeLa cells plated on monolayers of macrophages was completely inhibited
by peritoneal macrophages from mice receiving either WSDP, CAPE, or CA. Macrophages
from treated mice also inhibited [ (3)H]TdR incorporation into HeLa cells
in vitro. Testing for the possible presence of NO in the supernatants of 24
hours cultured macrophages activated with either compound revealed that the
toxicity of these cells to HeLa cells was in part due to the production of
NO. Tumour growth was suppressed by WSDP and its polyphenolic compounds given
orally to mice. Local presence of CA, and CAPE in the tissue, caused a significant
delay of tumour formation. Based on these results, we postulate that the antitumour
activity of the test compounds includes pronounced immunomodulatory activity
mainly due to the augmentation of non-specific antitumour resistance in mice
via macrophage activation and the production of soluble factors by those cells
which may interfere with either cells of the immune system or directly by
tumour cells. Abbreviations. WSDP:water-soluble derivative of propolis CA:caffeic
acid CAPE:caffeic acid phenethyl ester NO:nitric oxide NOS:nitric oxide syntase
[ (3)H]-TdR:[ (3)H]-thymidine.
PMID: 16450291 [PubMed - in process]
| 2: Radiat Prot Dosimetry. 2005;115(1-4):461-4. |
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Assessment by cytogenetic
analysis of the radioprotection properties of propolis extract.
Montoro A, Almonacid M,
Serrano J, Saiz M, Barquinero JF,
Barrios L, Verdu G, Perez J, Villaescusa JI.
Servicio de Proteccion Radiologica, Hospital la Fe, Av/Campanar no. 21, Valencia,
46009, Spain. almonpas@doctor.upv.es
Propolis obtained from honeybee hives has been used in folk medicine as an
anti-inflammatory, anti-carcinogenic or immunomodulatory agent. In animal
studies, the radioprotector effect of propolis has been attributed to its
free-radical scavenging properties. The present study was carried out to show
the protective properties of propolis extract against DNA damage induced by
gamma irradiation. The evaluation of the radioprotective effect of propolis
has been carried out by the analysis of chromosome aberration induction after
several doses of gamma rays. The results of an analysis in the presence of
ethanol extract of propolis (EEP) were compared with the dose-effect calibration
curve for gamma-rays by analysis of chromosome aberrations without propolis,
a decrease in the radiation-induced chromosome aberrations has been observed
to be higher than 50% for all the doses.
PMID: 16381767 [PubMed - in process]
| 3: J Ethnopharmacol. 2005 Nov 14; [Epub ahead of print] |
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Propolis: Effect of different
concentrations, extracts and intake period on seric biochemical variables.
Mani F, Damasceno HC,
Novelli EL, Martins EA, Sforcin JM.
Department of Chemistry and Biochemistry, Biosciences Institute, UNESP, 18600-000
Botucatu, SP, Brazil.
Propolis is a resinous substance produced by honeybees that possesses many
biological activities, such as antitumor, antioxidant, antimicrobial, anti-inflammatory,
and immunomodulatory, among others. The purpose of the present study was to
investigate the biochemical profile of propolis-treated rats to observe whether
propolis might lead to side effects after administration. Three different
treatments were analyzed: (1) rats were treated with different concentrations
of propolis (1, 3 and 6mg/kg/day) during 30 days; (2) rats were treated with
1mg/kg/day of ethanolic or water extracts of propolis (EEP, WEP) during 30
days; (3) rats were treated with 1mg/kg/day of ethanolic extract of propolis
during 90 and 150 days. Our results demonstrated no alterations in the seric
levels of cholesterol, HDL-cholesterol, total lipids, triglycerides and in
the specific activity of aminotransferases (AST) and lactic dehydrogenase
(LDH) of propolis-treated groups when compared to controls. On the basis of
our findings, since propolis does not induce any significant change in seric
parameters, it is claimed that long-term administration of propolis might
not have any cardiac injury.
PMID: 16293383 [PubMed - as supplied by publisher]
| 4: Vet Res Commun. 2005 Oct;29(7):575-93. |
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Peroral application of
water-soluble derivative of propolis (WSDP) and its related polyphenolic compounds
and their influence on immunological and antitumour activity.
Orsolic N, Sver L, Terzic S, Basic I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Rooseveltov trg 6, 10000 Zagreb, Croatia. norsolic@yahoo.com
Polyphenolic compounds are widely distributed in the plant kingdom and display
a variety of biological activities, including chemoprevention and growth inhibition
of tumours. Propolis contains a conglomerate of polyphenolic compounds. We
investigated the effect of propolis and polyphenolic compounds, components
of propolis, on the growth and metastatic potential of a transplantable mammary
carcinoma (MCa) of the mouse. Metastases in the lung were generated by 2 x
10(5) tumour cells injected intravenously (i.v.). A water-soluble derivative
of propolis (WSDP) and the polyphenolic compounds (caffeic acid (CA) and caffeic
acid phenethyl ester (CAPE)) were given to mice perorally before or after
tumour cell inoculation. WSDP, CA and CAPE reduced the number of metastases
in the lung. This implies that the antitumour activities of the compounds
used in these studies are mostly related to the immunomodulatory properties
of the compounds, their cytotoxicity to tumour cells, and their ability to
induce apoptosis and/or necrosis.
PMID: 16142606 [PubMed - in process]
| 5: Leuk Res. 2005 Nov;29(11):1343-6. |
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Evaluation of Manisa
propolis effect on leukemia cell line by telomerase activity.
Gunduz C, Biray C, Kosova B, Yilmaz B, Eroglu Z, Sahin F, Omay SB, Cogulu O.
Ege University, Faculty of Medicine, Department of Medical Biology, Izmir,
Turkey.
Propolis is a resinous substance which is used by bees to repair and maintain
their hives. It has more than 180 compounds including flavonoids, phenolic
acids and its esters which have anti-inflammatory, antibacterial, antiviral,
immunomodulatory, antioxidant and antiproliferative effects. Propolis is shown
to inhibit cell division and protein synthesis. However the exact mechanism
underlying antitumor effect is not clearly described. On the other hand progressive
telomere shortening to a critical level results with senescence of normal
cells by inducing apoptosis and telomerase prevents erosion of telomeres.
In this study we aimed to evaluate hTERT ratios in propolis-treated T-cell
acute lymphoblastic leukemia (CCFR-CEM) cell line. Cell counts and cell viability
of propolis-treated and propolis-free T-cell acute lymphoblastic leukemia
(CCFR-CEM) cell line were assessed by trypan blue dye exclusion test and MTT
assay. The LightCycler instrument was used (online real-time PCR) for the
quantification of hTERT in CCFR-CEM cell line. The hTERT ratio significantly
decreased 60 and 93% after 24 and 72 h respectively compared to the initial
value of the cells incubated with propolis. It had almost no cytotoxic effect
and caused 30, 30, 22 and 12% decrease in cell counts after 24, 48, 72 and
96 h respectively which is statistically significant. In conclusion propolis
may show antitumor and apoptotic effect via inhibiting telomerase expression
besides the mechanisms which have been described previously.
PMID: 16055186 [PubMed - indexed for MEDLINE]
| 6: Pulm Pharmacol Ther. 2006;19(2):90-5. Epub 2005 Jun 13. |
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Effects of caffeic acid
phenethyl ester on lipopolysaccharide-induced lung injury in rats.
Koksel O, Ozdulger A, Tamer L, Cinel L, Ercil M, Degirmenci U,
Unlu S, Kanik A.
Department of Thoracic Surgery, Mersin University School of Medicine, Zeytinabahce
Caddesi, 33079 Mersin, Turkey.
Extracts of propolis, a natural beehive product, have been known for centuries
to have a variety of beneficial medical properties, among which their anti-inflammatory
effect is a major one. Caffeic acid phenethyl ester (CAPE), an active propolis
component, has antimicrobial, anti-inflammatory, antioxidant, carcinostatic
and immunomodulatory properties. In this study, we aimed to investigate the
efficacy of CAPE in endotoxin-induced lung injury in rats. Lung injury was
induced by a footpad injection of lipopolysaccharide (LPS). In the treatment
group, 10mumolkg(-1) CAPE was injected intraperitoneally immediately after
LPS injection. At 24h after LPS and/or CAPE injection, blood and lung tissue
specimens were collected. MDA levels and MPO activity in serum and lung tissue,
serum total antioxidant levels, lung tissue Na(+)/K(+) ATP-ase activity and
histopathological evaluation were determined to assess the efficacy of CAPE
treatment. CAPE was found to be efficient in reducing inflammation and lung
tissue damage induced by LPS in rats.
PMID: 15953745 [PubMed - in process]
| 7: Neurosci Lett. 2005 Jul 22-29;383(1-2):39-43. |
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The flavanoide caffeic
acid phenethyl ester blocks 6-hydroxydopamine-induced neurotoxicity.
Noelker C, Bacher M, Gocke P, Wei X, Klockgether T,
Du Y, Dodel R.
Department of Neurology, Friedrich-Wilhelms-University, Bonn, Germany.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by
progressive loss of dopaminergic (DA) neurons of the substantia nigra pars
compacta. 6-Hydroxydopamine (6-OHDA) is specific to dopaminergic neurons in
intrastriatal rodent models. It induces neuronal death either via uncoupling
mitochondrial oxidative phosphorylation resulting in energy deprivation or
alternatively, is associated with its ability to produce hydrogen peroxide,
hydroxyl and superoxide radicals. Caffeic acid phenethyl ester (CAPE), an
antioxidant flavanoid, has antiviral, anti-inflammatory, antioxidant, and
immunomodulatory properties. Recent studies have shown that CAPE has also
a neuroprotective effects in ischemia and low potassium-induced neuronal apoptotic
models. In cerebellar granule neurons CAPE significantly blocks 6-OHDA mediated
cell death (70 microM) in a dose-dependent manner. Furthermore, CAPE was able
to modulate the Ca(2+)-induced release of cyctochrome c in isolated liver
mitochondria. Caspase-3 activation following 6-OHDA treatment was markedly
inhibited in the presence of CAPE. Although the molecular mechanisms associated
with CAPE's neuroprotective effects remain to be elucidated in more detail,
our results clearly demonstrate a considerable neuroprotective effect of CAPE.
Since a mitochondrial insult is a major cause for the degeneration of nigral
neurons in PD, we hypothesize that propolis derivatives, in particular CAPE,
may have a neuroprotective effect on those cells and may be a promising drug
candidate to be taken into in vivo models of PD.
PMID: 15894425 [PubMed - indexed for MEDLINE]
| 8: J Ethnopharmacol. 2005 Apr 26;98(3):301-5. |
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Effect of propolis, some
isolated compounds and its source plant on antibody production.
Sforcin JM, Orsi RO, Bankova V.
Department of Microbiology and Immunology, Biosciences Institute, UNESP, 18618-000
Botucatu, S.P., Brazil.
Propolis is a beehive product with a very complex chemical composition, widely
used in folk medicine because of its several therapeutic activities. Its biological
properties and chemical composition may vary according to the geographic location
and to the different plant sources. The possible mechanism of action of propolis
as well as of its active compounds has been the subject of researchers in
recent years. In this work, first we reported the results of our study on
the seasonal effect of the immunomodulatory action of propolis on antibody
production in bovine serum albumin (BSA)-immunized rats. Then, we compared
the effect of Brazilian and Bulgarian propolis, some isolated compounds and
Baccharis extract on anti-BSA antibody levels. Based on the results, we conclude
that propolis stimulates antibody production, independently of the season
and geographic origin. Caffeic acid, quercetin and Baccharis extract had no
effect on antibody production, although the importance of isolated compounds
is well reported in other biological assays. Propolis action is a consequence
of plant-derived products with synergic effects, while isolated compounds
or extracts from its plant sources had no effect in this assay.
PMID: 15814263 [PubMed - indexed for MEDLINE]
| 9: 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]
| 10: Clin Biochem. 2005 Feb;38(2):191-6. |
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Effects of caffeic acid
phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic
rat heart.
Okutan H, Ozcelik N, Yilmaz HR, Uz E.
Department of Cardiovascular Surgery, Suleyman Demirel University Medical
School, 6 Mart Ataturk C. Istiklal M. Oztunc A., No:1 D:4 32050 Isparta, Turkey.
okutanh@yahoo.com
OBJECTIVES: The risk for cardiovascular disease is significantly high in diabetes
mellitus. Experimental evidence suggests that oxidative stress plays a dominant
role in the pathogenesis of diabetes mellitus. Caffeic acid phenethyl ester
(CAPE), an active component of propolis, has several biological and pharmacological
properties, including antioxidant, anti-inflammatory, anti-carcinogenic, antiviral,
and immunomodulatory activities. In light of the antioxidant ability of CAPE,
the effects of CAPE on the antioxidative status of cardiac tissue were investigated
in streptozotocin (STZ)-induced diabetic rats. DESIGN AND METHODS: Twenty-six
rats were randomly divided into three groups: group I, control, nondiabetic
rats (n = 9); group II, STZ-induced, untreated diabetic rats (n = 7); and
group III, STZ-induced, CAPE-treated diabetic rats (n = 10). In groups II
and III, diabetes developed 3 days after intraperitoneal (ip) administration
of a single 35 mg kg(-1) dose of STZ. Thereafter, while the rats in group
II received no treatment, the rats in group III began to receive a 10 mumol
kg(-1) ip dose of CAPE per day. After 8 weeks, the levels of malondialdehyde
(MDA) and the activities of superoxide dismutase (SOD), catalase (CAT), and
glutathione peroxidase (GSH-Px) in the cardiac tissues of all groups were
analyzed. RESULTS: In untreated diabetic rats, MDA markedly increased in the
cardiac tissue compared with the control rats (P < 0.05). However, MDA
levels were reduced to the control level by CAPE. The activities of SOD and
CAT in the untreated diabetic group and the CAPE-treated diabetic group were
higher than those of the control group (P < 0.05). Rats in the CAPE-treated
diabetic group had reduced activities of SOD and CAT in comparison with the
rats in the untreated diabetic group (P < 0.05). There were no significant
differences in the activity of GSH-Px between the rats in the untreated diabetic
group and the control group. However, the activity of GSH-Px was increased
in CAPE-treated diabetic rats compared with the control and untreated diabetic
rats (P < 0.05). CONCLUSION: These results reveal that diabetes mellitus
increases oxidative stress in cardiac tissue and CAPE has an ameliorating
effect on the oxidative stress via its antioxidant property.
PMID: 15642285 [PubMed - indexed for MEDLINE]
| 11: J Sep Sci. 2004 May;27(7-8):619-23. |
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Quantitative analysis of caffeic
acid phenethyl ester in crude propolis by liquid chromatography-electrospray
ionization mass spectrometry.
Del Boccio P,
Rotilio D.
Gennaro Paone Environmental Health Center, Mario Negri Institute for Pharmacological
Research, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Caffeic acid phenethyl ester (CAPE), an active component of propolis from
honeybee hives, is known to have antimitogenic, anticarcinogenic, antinflammatory,
and immunomodulatory properties. The paper describes a rapid and simple liquid
chromatography-electrospray ionisation mass spectrometry method for qualitative
and quantitative determination of CAPE. The chromatographic separation was
performed with a Luna RP-C18 column using a water-acetonitrile linear gradient.
The method was linear over a 0.125-80 ng/mL range (LOD = 62.5 pg/mL). The
method was applied for the quantitation of caffeic acid phenethyl ester in
crude propolis samples, which were analysed directly after extraction with
ethyl acetate solution.
PMID: 15335050 [PubMed - indexed for MEDLINE]
| 12: J Ethnopharmacol. 2004 Oct;94(2-3):307-15. |
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Immunomodulatory and
antimetastatic action of propolis and related polyphenolic compounds.
Orsolic N, Knezevic AH,
Sver L, Terzic S, Basic I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Rooseveltov trg 6, 10000, Croatia. norsolic@yahoo.com
The effect of polyphenolic compounds isolated from propolis and propolis itself
was investigated on the growth and metastatic potential of a transplantable
mammary carcinoma (MCa) of CBA mouse. Metastases in the lung were generated
by intravenous injection of tumor cells (2 x 10(5)). A water-soluble derivative
of proplis (WSDP), caffeic acid (CA), caffeic acid phenethyl ester (CAPE)
and quercetin (QU) were given to mice per os before tumor cells inoculation.
Tested compounds significantly decreased the number of tumor nodules in the
lung. According to the results obtained the antitumor activity of tested compounds
can be related to the immunomodulatory properties of the compounds, their
cytotoxicity to tumor cells, and their capacity to induce apoptosis and necrosis.
The experimental data support that WSDP, CA, CAPE and QU could be potentially
useful in the control of tumor growth in experimental models.
PMID: 15325736 [PubMed - indexed for MEDLINE]
| 13: Nutr Cancer. 2003;47(2):156-63. |
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Inhibitory effect of water-soluble
derivative of propolis and its polyphenolic compounds on tumor growth and
metastasizing ability: a possible mode of antitumor action.
Orsolic N, Sver L, Terzic S, Tadic Z, Basic I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Zagreb, Croatia. norsolic@yahoo.com
Polyphenolic compounds are widely distributed in the plant kingdom and display
a variety of biological activities, including chemoprevention and tumor growth
inhibition. Propolis is made up of a variety of polyphenolic compounds. We
compared how the routes of administration of polyphenolic compounds deriving
from propolis and of propolis itself affect the growth and metastatic potential
of a transplantable mammary carcinoma (MCa) of the CBA mouse. The influence
of tested compounds on local tumor growth was also studied. Metastases in
the lung were generated by 2 x 10(5) tumor cells injected intravenously (IV).
A water-soluble derivative of propolis (WSDP) and polyphenolic compounds (caffeic
acid, CA, and CA phenethyl ester, CAPE) were given to mice per os (PO) or
intraperitoneally (IP) before or after tumor cell inoculation. Tested compounds
significantly decreased the number of lung colonies. When mice were inoculated
with 10(5) MCa cells in the exact site of subcutaneous injection of different
doses of WSDP, CA, or CAPE, tumor growth was inhibited, and survival of treated
mice was prolonged. Antitumor activity, according to the results obtained,
is mostly related to the immunomodulatory properties of the compounds and
their capacity to induce apoptosis and necrosis. In conclusion, results presented
here indicate that WSDP, CA, and CAPE could be potential useful tools in the
control of tumor growth in experimental tumor models when administrated PO;
because PO administration is the easiest way of introducing a compound used
for prevention and/or cure of any disease, it is likely that this article
has reached the goal of the investigation.
PMID: 15087268 [PubMed - indexed for MEDLINE]
| 14: Int Immunopharmacol. 2004 Mar;4(3):429-36. |
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Immunomodulatory effect
of caffeic acid phenethyl ester in Balb/c mice.
Park JH, Lee JK, Kim HS, Chung ST, Eom JH, Kim KA, Chung SJ, Paik SY, Oh HY.
Immunotoxicology Division, Department of Toxicology, National Institute of
Toxicological Research, KFDA, Nokbun-Dong, Eunpyung-Gu, Seoul 122-704, South
Korea. jaehyun@kfda.go.kr
Caffeic acid phenethyl ester (CAPE), an the active component of propolis,
is known to have anticarcinogenic, antiviral and various biological activities;
however, the effect of CAPE on the immunomodulatory activity in vivo remains
unknown. We have investigated the effect of CAPE on the immune system in female
Balb/c mice. CAPE (0, 5, 10, 20 mg/kg) was given to mice orally for 14 days.
Immunomodulatory activity was evaluated by assessment of body and organ weight,
lymphocyte blastogenesis, plaque-forming cell (PFC) assay, lymphocyte subpopulation
by flow cytometry and cytokine production. Even though the change of body
weight was not observed in CAPE-administered group, thymus weight and/or cellularity
of thymus and spleen are decreased at the all dose groups of CAPE (5, 10,
20 mg/kg). On the other hand, CAPE had no effect on B lymphocyte proliferation
induced by lipopolysaccharide (LPS) but increased T lymphocyte blastogenesis
induced by concanavalin A (Con A) at the dose of 20 mg/kg. In the case of
lymphocyte subpopulation, the population of T and B cells was not changed
but CD4(+) T cell subsets are significantly increased in exposure to CAPE.
The antibody responses to T lymphocyte dependent antigen, sheep red blood
cell and keyhole limpet hemocyanin (KLH) were increased more than 10 mg/kg
in CAPE-treated group. Likewise, the cytokine, IL-2, IL-4 and IFN-gamma were
significantly increased at the dose of 20 mg/kg CAPE group. These results
suggest that CAPE could have immunomodulatory effects in vivo.
PMID: 15037220 [PubMed - indexed for MEDLINE]
| 15: J Ethnopharmacol. 2004 Mar;91(1):25-30. |
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Effects of ethanol extract
of propolis (EEP) and its flavones on inducible gene expression in J774A.1
macrophages.
Blonska M, Bronikowska J,
Pietsz G, Czuba ZP, Scheller S, Krol W.
Department of Microbiology and Immunology, Medical University of Silesia,
ul Jordana 19, Zabrze-Rokitnica 41-808, Poland.
Propolis, a bee-hive product, has been used in folk medicine for centuries,
and recently in modern medicine as an anti-inflammatory and immunomodulatory
agent. These activities would be mainly due to phenolic compounds such as
flavonoids, especially flavone derivatives. The present study examined the
effect of ethanol extract of propolis (EEP) and selected flavone derivatives
(chrysin, galangin, kaempferol and quercetin) on interleukin-1beta (IL-1beta)
and inducible nitric oxide synthase (iNOS) gene expression in lipopolysaccharide
(LPS)-induced J774A.1 macrophages. Treatment of cells with EEP significantly
suppressed both IL-1beta mRNA (P<0.02) and iNOS mRNA (P<0.001) expression.
The concentrations of cytokine in cell culture supernatants and cell lysates
and nitric oxide (NO) generation were reduced in a dose-dependent manner.
The tested phenolic compounds significantly decreased the IL-1beta mRNA level
and IL-1beta protein concentration (P<0.05) (excluding galangin), iNOS
mRNA level and NO production (P<0.001). The most potent inhibitor of the
IL-1beta synthesis and NO generation was chrysin. These results indicate that
EEP exerts its inhibitory effect on the IL-1beta and iNOS gene expression
in J774A.1 macrophages at the transcriptional level. Tested flavone derivatives
contribute to the anti-inflammatory activity of propolis.
PMID: 15036463 [PubMed - indexed for MEDLINE]
| 16: J Pharmacol Exp Ther. 2004 Mar;308(3):993-1001. Epub 2003 Nov 14. |
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Caffeic acid phenethyl
ester inhibits T-cell activation by targeting both nuclear factor of activated
T-cells and NF-kappaB transcription factors.
Marquez N, Sancho R, Macho A, Calzado MA, Fiebich BL, Munoz E.
Departamento de Biologia Celular, Fisiologia e Inmunologia. Facultad de Medicina,
Cordoba, Spain.
Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of
honeybee hives, has been shown to reveal anti-inflammatory properties. Since
T-cells play a key role in the onset of several inflammatory diseases, we
have evaluated the immunosuppressive activity of CAPE in human T-cells, discovering
that this phenolic compound is a potent inhibitor of early and late events
in T-cell receptor-mediated T-cell activation. Moreover, we found that CAPE
specifically inhibited both interleukin (IL)-2 gene transcription and IL-2
synthesis in stimulated T-cells. To further characterize the inhibitory mechanisms
of CAPE at the transcriptional level, we examined the DNA binding and transcriptional
activities of nuclear factor (NF)-kappaB, nuclear factor of activated cells
(NFAT), and activator protein-1 (AP-1) transcription factors in Jurkat cells.
We found that CAPE inhibited NF-kappaB-dependent transcriptional activity
without affecting the degradation of the cytoplasmic NF-kappaB inhibitory
protein, IkappaBalpha. However, both NF-kappaB binding to DNA and transcriptional
activity of a Gal4-p65 hybrid protein were clearly prevented in CAPE-treated
Jurkat cells. Moreover, CAPE inhibited both the DNA-binding and transcriptional
activity of NFAT, a result that correlated with its ability to inhibit phorbol
12-myristate 13-acetate plus ionomycin-induced NFAT1 dephosphorylation. These
findings provide new insights into the molecular mechanisms involved in the
immunomodulatory and anti-inflammatory activities of this natural compound.
PMID: 14617683 [PubMed - indexed for MEDLINE]
| 17: J Ethnopharmacol. 2003 Jul;87(1):93-7. |
Propolis: lymphocyte
proliferation and IFN-gamma production.
Sa-Nunes A, Faccioli LH,
Sforcin JM.
Department of Clinical Analysis, Toxicology and Bromatology, School of Pharmaceutical
Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo,
Brazil.
We evaluated propolis influence on polyclonal activation of lymphocytes by
concanavalin A (Con A). The in vitro experiments showed that propolis decreases
splenocyte proliferation both in the absence or presence of Con A. The suppression
in mitogen-induced splenocyte proliferation also occurred when mice were treated
intraperitoneally with propolis for 3 days. An increased of IFN-gamma production
in the culture supernatants of the same cells was observed. A dual action
of propolis on lymphocyte activation was proposed: it decreases splenocyte
proliferation in the presence or absence of Con A and stimulates IFN-gamma
production by spleen cells. These results are important to understand the
immunomodulatory action of propolis on the host's specific and non-specific
immunity.
PMID: 12787960 [PubMed - indexed for MEDLINE]
| 18: J Ethnopharmacol. 2003 Feb;84(2-3):265-73. |
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Immunomodulation by water-soluble
derivative of propolis: a factor of antitumor reactivity.
Orsolic N, Basic I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Rooseveltov trg 6, 10 000 Zagreb, Croatia. norsolic@yahoo.com
The antimetastatic efficacy of a water-soluble derivative of propolis (WSDP)
was studied. Tumor was a transplantable mammary carcinoma of CBA mouse. Metastases
in the lung were generated by 2 x 10(5) viable tumor cells i.v. WSDP was given
intraperitoneally at doses of 50 or 150 mg/kg before or after tumor cell inoculation.
Therapies reduced the number of metastases in the lung and tumor growth was
suppressed significantly by WSDP. It is likely that antimetastatic activity
of the WSDP is mainly mediated by immunomodulatory activity. Changes in several
immunological parameters such as production of lymphocyte activating factor
by peritoneal macrophages and the efficacy of those macrophages to kill tumor
cell in vitro, responses of lymphocytes to mitogen, and weight and cellularity
of spleen, respectively, correlated well with antimetastatic properties of
the WSDP. Based on results we postulate that the antimetastatic activity of
propolis includes a pronounced immunomodulatory activity mainly toward augmentation
of nonspecific antitumor resistance in mice via macrophage activation. Copyright
2002 Elsevier Science Ireland Ltd.
PMID: 12648825 [PubMed - indexed for MEDLINE]
| 19: Fitoterapia. 2002 Nov;73 Suppl 1:S1-6. |
Related Articles, Links |
Propolis, an old remedy
used in modern medicine.
Castaldo S, Capasso F.
Department of I.N.P.S. of Naples, via Medina 63, Naples, Italy.
Propolis is one of the few natural remedies that has maintained its popularity
over a long period of time. The pharmacologically active molecules in the
propolis are flavonoids and phenolic acids and their esters. These components
have multiple effects on bacteria, fungi and viruses. In addition, propolis
and its components have anti-inflammatory and immunomodulatory activities.
Moreover, propolis has been shown to lower blood pressure and cholesterol
levels. However, clinical studies to substantiate these claims are required.
Publication Types:
· Review
PMID: 12495704 [PubMed - indexed for MEDLINE]
| 20: J Ethnopharmacol. 2002 Oct;82(2-3):89-95. |
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Estrogenic effects of
ethanol and ether extracts of propolis.
Song YS, Jin C, Jung KJ, Park EH.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science
and Technology, P.O. Box 131, Cheongryang, Seoul, South Korea.
Propolis obtained from honeybee hives has been used in Oriental folk medicine
as an anti-inflammatory, anti-carcinogenic, or immunomodulatory agent. The
potential estrogenic activity of propolis was investigated in vitro using
the MCF-7 human breast cancer cell proliferation, human estrogen receptor
(hER) binding and yeast-based steroid receptor transcription, and in vivo
using the immature rat uterotrophic effect. Treatments with ethanol extract
of propolis (EEP) and ether extract of propolis (REP) enhanced MCF-7 cell
proliferation in concentrations ranging from 0.8 to 4 microg/ml. Both EEP
and REP competed for binding of [3H]17beta-estradiol to the hER with IC(50)
values of 9.14 and 9.72 microg/ml, respectively. In yeast estrogen receptor
transcription assay, both EEP and REP were found to be estrogenic with EC(50)
values of 9.48, and 8.55 microg/ml, respectively. Animals treated with EEP
or REP for 4 days (500-1000 mg/kg per day, s.c.) exhibited significant dose-dependent
increases in uterine wet weight. However, in the yeast androgen and progesterone
receptor transcription assays, either EEP or REP was found not to be active.
The results suggest that propolis produces estrogenic effects through activation
of estrogen receptors.
PMID: 12241982 [PubMed - indexed for MEDLINE]
| 21: Arch Pharm Res. 2002 Aug;25(4):500-4. |
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Inhibition of angiogenesis by
propolis.
Song YS, Park EH, Jung KJ, Jin C.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science
and Technology, Cheongryang, Seoul.
Propolis, obtained from honeybee hives, has been used in Oriental folk medicine
as an anti-inflammatory, anti-carcinogenic, and immunomodulatory agent. There
is considerable evidence suggesting that angiogenesis and chronic inflammation
are codependent. Blockage of angiogenesis results in an anti-inflammatory
effect. Ethanol (EEP) and ether extracts of propolis (REP), and caffeic acid
phenethyl ester (CAPE), an active component of propolis, were examined for
their anti-angiogenic activities using the chick embryo chorioallantoic membrane
(CAM), and the calf pulmonary arterial endothelial (CPAE) cell proliferation,
assays. The presence of EEP, REP and CAPE inhibited angiogenesis in the CAM
assay and the proliferation of CPAE cells. The results suggest that anti-angiogenic
activities of EEP, REP and CAPE are also responsible for their anti-inflammatory
effect.
PMID: 12214863 [PubMed - indexed for MEDLINE]
| 22: J Ethnopharmacol. 2002 May;80(2-3):155-61. |
Ethanol extract of propolis
inhibits nitric oxide synthase gene expression and enzyme activity.
Song YS, Park EH, Hur GM, Ryu YS, Kim YM, Jin C.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science
and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, South Korea.
Propolis obtained from honeybee hives has been used in Oriental folk medicine
as an anti-inflammatory, anti-carcinogenic, or immunomodulatory agent. However,
the molecular basis for anti-inflammatory properties of propolis has not yet
been established. Since nitric oxide (NO) synthesized by inducible nitric
oxide synthase (iNOS) has been known to be involved in inflammatory and autoimmune-mediated
tissue destruction, modulation of NO synthesis or action represents a new
approach to the treatment of inflammatory and autoimmune diseases. The present
study, therefore, examined effects of ethanol extract of propolis (EEP) on
iNOS expression and activity of iNOS enzyme itself. Treatment of RAW 264.7
cells with EEP significantly inhibited NO production and iNOS protein expression
induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). EEP
also inhibited iNOS mRNA expression and nuclear factor-kappa B (NF-kappaB)
binding activity in a concentration-dependent manner. Furthermore, transfection
of RAW 264.7 cells with iNOS promoter linked to a chloramphenicol acetyltransferase
(CAT) reporter gene, revealed that EEP inhibited the iNOS promoter activity
induced by LPS plus IFN-gamma through the NF-kappaB sites of the iNOS promoter.
In addition, EEP directly interfered with the catalytic activity of murine
recombinant iNOS enzyme. These results suggest that EEP may exert its anti-inflammatory
effect by inhibiting the iNOS gene expression via action on the NF-kappaB
sites in the iNOS promoter and by directly inhibiting the catalytic activity
of iNOS.
PMID: 12007705 [PubMed - indexed for MEDLINE]
| 23: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9090-5. |
Related Articles, Links |
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]
| 24: J Ethnopharmacol. 1995 Jul 28;47(3):145-7. |
Related Articles, Links |
Immunomodulatory action
of propolis. VI. Influence of a water soluble derivative on complement activity
in vivo.
Ivanovska ND,
Dimov VB, Bankova VS, Popov SS.
Department of Immunology, Bulgarian Academy of Sciences, Sofia.
The water soluble derivative (WSD) of propolis in a dose of 150 mg/kg was
administered intravenously (i.v.), intraperitoneally (i.p.) and orally (p.o.)
to mice. The alteration of serum alternative pathway (AP) complement level
was observed. The WSD also influenced the process of acute inflammation provoked
by zymosan in mice. The effect was strongly dependent on the route of WSD
administration.
PMID: 8569238 [PubMed - indexed for MEDLINE]
| 25: J Ethnopharmacol. 1995 Jul 28;47(3):135-43. |
Related Articles, Links |
Immunomodulatory action
of propolis. V. Anticomplementary activity of a water-soluble derivative.
Ivanovska ND,
Dimov VB, Pavlova S, Bankova VS, Popov SS.
Department of Immunology, Bulgarian Academy of Sciences, Sofia.
The effect of a water-soluble derivative (WSD) of propolis on the classical
pathway (CP) and the alternative (AP) complement activity has been investigated.
The in vitro experiments show that WSD inhibits both pathways and the effect
depends on the source of complement. The suppression of complement-mediated
haemolysis proves to be time- and temperature-related. High WSD concentrations
cause direct damage of the target erythrocytes. The estimation of C3-residual
activity indicates that the preparation diminishes C3 functional activity.
PMID: 8569237 [PubMed - indexed for MEDLINE]
| 26: Vaccine. 1992;10(12):817-23. |
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Immunomodulatory
action of propolis: IV. Prophylactic activity against gram-negative infections
and adjuvant effect of the water-soluble derivative.
Dimov
V, Ivanovska
N, Bankova
V, Popov
S.
Department of Immunology, Institute of Microbiology, Bulgarian Academy of
Sciences, Sofia.
The efficacy of the water-soluble derivative (WSD) of natural propolis (bee
glue) was examined for augmentation of host resistance against experimental
infections caused by Gram-negative pathogens (Klebsiella pneumoniae, Proteus
vulgaris, Escherichia coli, Pseudomonas aeruginosa). The substance was found
to induce significant non-specific protection, but did not inhibit the in
vitro growth of the same strains. Pretreatment with WSD prior to the standard
scheme for tumour necrosis factor (TNF) induction (BCG and two weeks later
lipopolysaccharide (LPS)) provoked an interval-dependent reduction in the
lytic capacity of serum against L 929 target cells. The replacement of the
triggering or priming signal with WSD markedly increased TNF production. In
vivo administration of WSD led to a rapid and route-dependent change in the
alternative complement pathway haemolysis. The
alteration in C1q complement component and total protein synthesis, and also
in nitroblue tetrazolium reduction, suggests that macrophage activation makes
a major contribution to the capacity of WSD to prevent infections.
PMID: 1455907 [PubMed - indexed for MEDLINE]