Porpolisin Antiviral Etkinliği

Antimicrobial activity of flavonoids.

Cushnie TP, Lamb AJ.

Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

PMID: 16323269 [PubMed - indexed for MEDLINE]

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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]

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Anti-HIV-1 activity of propolis in CD4(+) lymphocyte and microglial cell cultures.

Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK.

Neuroimmunology Laboratory, Minneapolis Medical Research Foundation, Minneapolis, MN 55415, USA; Centre for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, Minneapolis, MN 55415, USA.

An urgent need for additional agents to treat human immunodeficiency virus type 1 (HIV-1) infection led us to assess the anti-HIV-1 activity of the natural product propolis in CD4(+) lymphocytes and microglial cell cultures. Propolis inhibited viral expression in a concentration-dependent manner (maximal suppression of 85 and 98% was observed at 66.6mug/ml propolis in CD4(+) and microglial cell cultures, respectively). Similar anti-HIV-1 activity was observed with propolis samples from several geographic regions. The mechanism of propolis antiviral property in CD4(+) lymphocytes appeared to involve, in part, inhibition of viral entry. While propolis had an additive antiviral effect on the reverse transcriptase inhibitor zidovudine, it had no noticeable effect on the protease inhibitor indinavir. The results of this in vitro study support the need for clinical trials of propolis or one or more of its components in the treatment of HIV-1 infection.

PMID: 16046088 [PubMed - in process]

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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 granuleneurons 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]

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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]

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[Investigation of chemical composition of propolis extract]

[Article in Lithuanian]

Majiene D, Trumbeckaite S, Grunoviene D, Ivanauskas L, Gendrolis A.

Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania.

Propolis is a natural product, produced by bees and containing exudates from plants, mixed with bee wax. Propolis and its ethanolic extract are usually used for treatment and prevention of different diseases. Propolis has antibacterial, antiviral, antifungal, anti-inflammatory, anesthetic and immunomodulating properties. Till now there is no data about chemical composition of Lithuanian propolis. Thus, the aim of our work was to investigate the chemical composition of Lithuanian propolis and its ethanolic extract by using gas chromatography / mass spectrometry. We found, that the main structural types of compounds were terpenoids, aromatic and aliphatic acid esters. The most of terpenoids were mono- and sesquiterpens: azulene, alpha-bisabolol, citral, valerenol, etc. Thus, our data show, that the composition of propolis is various and depends on the origin of plants, from where propolis was collected.

PMID: 15299997 [PubMed - indexed for MEDLINE]

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Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats.

Ilhan A, Akyol O, Gurel A, Armutcu F, Iraz M, Oztas E.

Department of Neurology, Inonu University, Turgut Ozal Medical Center, Malatya, Turkey. ailhan@inonu.edu.tr

Because oxidative damage has been known to be involved in inflammatory and autoimmune-mediated tissue destruction, modulation of oxygen free radical production represents a new approach to the treatment of inflammatory and autoimmune diseases. Central nervous system tissue is particularly vulnerable to oxidative damage, suggesting that oxidation plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, has been determined to have antioxidant, anti-inflammatory, antiviral, and anticancer activities. We have previously reported that CAPE inhibits ischemia-reperfusion injury and oxidative stress in rabbit spinal cord tissue. The present study, therefore, examined effects of CAPE on oxidative tissue damage in EAE in rats. Treatment with CAPE significantly inhibited reactive oxygen species (ROS) production induced by EAE, and ameliorated clinical symptoms in rats. These results suggest that CAPE may exert its anti-inflammatory effect by inhibiting ROS production at the transcriptional level through the suppression of nuclear factor kappaB activation, and by directly inhibiting the catalytic activity of inducible nitric oxide synthase.

PMID: 15223072 [PubMed - indexed for MEDLINE]

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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]

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Spasmolysis of combined bee glue and Shaoyao-Gancao-tang on isolated rabbit jejunum.

Wang NZ, Li D.

Dept of Food Science, Hangzhou University of Commerce, Hangzhou, China 310035.

Background - Propolis (bee glue) is a valuable byproduct of apiculture, which is found in honeybee hives. It has been suggested that propolis-ethanol-extract has antitumour, antimicrobial, antifungal, antiviral, antihepatotoxic, antioxidative, and anti-inflammatory activities. Shaoyao-Gancao-tang, a prescription of Chinese Medicine, consists of water extract of liquorice (Radix Glycyrrhizac) and peony (Paeonialaciflora) roots. Objective - To investigate the effect of combined propolis-ethanol-extract and Shaoyao-Gancao-tang (PSG) on contraction of isolated rabbit jejunum in vitro. Design - PGS was prepared from the ethanol extract of propolis and water extract of 1:1 liquorice and peony roots. One end of the jejunum tube (3-4cm) was fastened to the ventilating pipe of a thermostatic bath, the other end to the tensioning exchanger, which was connected to a Recorder. Outcomes - With the same concentration (0.02%), PSG showed a 31% reduction on the maximum relaxation time compared with propolis-ethanol-extracts or Shaoyao-Gancao-tang (P<0.01, n= 10). This result indicates that there was a synergistic effect between propolis-ethanol-extracts and Shaoyao-Gancao-tang on the myenteric relaxation of jejunum in vitro. Conclusions - The action of PSG on jejunum smooth muscles is most likely through M-receptors, since acetylcholine induced jejunum contractions were significantly decreased by PSG, and there was a remarkable synergistic effect between atropine and PSG (P<0.001, n= 8). In conclusions, the PGS showed an antispasmodic activity, and inhibits peristalsis of jejunum smooth muscles via inhibiting M-receptors.

PMID: 15023697 [PubMed - in process]

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Protective role of Egyptian propolis against tumor in mice.

El-khawaga OA, Salem TA, Elshal MF.

Chemistry Department, Faculty of Science, Mansoura University, Mansoura City, Egypt. elkhawaga70s@mans.edu.eg

BACKGROUND: Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties. The present work is aimed to study the effect of crude Egyptian propolis on tumor in mice induced by Ehrlich ascitis carcinoma (EAC) cell line. RESULTS: The administration of propolis (160 mg/kg body weight), by gastric intubation 2 h before the intraperitoneal injection of EAC, effectively inhibited tumor growth and the proliferation of EAC. The tumor volume was markedly reduced from 7+/-0.9 ml in EAC-infected mice to 1.6+/-0.95 ml in propolis-treated mice. Also, the lipid peroxide level which was 13.3+/-1.24 nmol malodialdehyde (MDA)/mg protein in EAC infected mice was significantly decreased to 3.3+/-2.1 nmol MDA/mg protein. Reduced glutathione (GSH) and glutathione S-transferase (GST) concentrations were markedly increased in propolis-treated mice. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Administration of propolis 2 h before injection of EAC arrested cells in G0/G1 phase and resulted in a decrease in the viability, DNA, total RNA and protein level of tumor cells. CONCLUSIONS: Crude Egyptian propolis has a strong inhibitory activity against tumors. The anti-tumor mechanism may be mediated by preventing oxidative damage and induction of apoptosis.

PMID: 14637260 [PubMed - indexed for MEDLINE]

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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 thatCAPE 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]

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In vitro permeation through porcine buccal mucosa of caffeic acid phenetyl ester (CAPE) from a topical mucoadhesive gel containing propolis.

Ceschel GC, Maffei P, Sforzini A, Lombardi Borgia S, Yasin A, Ronchi C.

Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Via San Donato 19/2, 4100, Bologna, Italy. Paolam@biofarm.unibo.it

Recent studies have shown that propolis has on the oral cavity appreciable antibacterial, antifungal and antiviral actions, as well as anti-inflammatory, anaesthetic and cytostatic properties. In light of these studies, an assessment of the diffusion and permeation of caffeic acid phenetyl ester (CAPE) through porcine buccal mucosa was considered useful as a possible application in the stomatological field. To do so, a mucoadhesive topical gel was prepared to apply to the buccal mucosa. The gel was formulated in such a way as to improve the solubility of the propolis, conducting to an increase of the flux. The mucosal permeation of CAPE from the formulation was evaluated using Franz cells, with porcine buccal mucosa as septum between the formulation (donor compartment) and the receptor phase chamber. The diffusion through the membrane was determined by evaluating the amount of CAPE present in the receiving solution, the flux and the permeation coefficient (at the steady state) in the different formulations at set intervals. Qualitative and quantitative determinations were done by HPLC analysis. From the results, CAPE allowed a high permeability coefficient in comparison to the coefficient of other molecules, as expected from its physical-chemical structure. Moreover, the developed gel improved the CAPE flux approximately 35 times more with respect to an ethanol solution formulated at the same gel concentration. The developed gel was also tested in order to evaluate the mucoadhesive behaviour and comfort in vivo on 10 volunteers in a period of 8 h. The in vivo evaluation of mucoadhesive gel revealed adequate comfort and non-irritancy during the period of study and it was well accepted by the volunteers.

PMID: 12495709 [PubMed - indexed for MEDLINE]

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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. alrusso@mbow.unict.it

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]

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Anti-herpes simplex virus effect of an aqueous extract of propolis.

Huleihel M, Isanu V.

Institute for Applied Biosciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. mahmoudh@bgumail.bgu.ac.il

BACKGROUND: Propolis, a natural product from beehives, comprises a complex of chemicals, the most important group being flavinoids, which play a role in antiviral protection. OBJECTIVES: To test the inhibitory effect of propolis extract against herpes simplex viruses in vitro and in vivo. METHODS: In vitro: propolis was added to Vero cells at various times and concentrations before, at or after infection with HSV-1. In vivo: the effect of propolis was tested in newborn rats infected s.c. or i.p. and on rabbit come as infected with HSV-1. RESULTS: In vitro: 0.5% propolis extract caused 50% inhibition of HSV infection. There was indirect evidence for a strong interaction between the propolis extract and the surface of the Vero cells, but there was no direct interaction with HSV-1 particles. Administration of propolis before or at the time of infection yielded the most significant inhibitory effect, but even when 10% propolis extract was added 2 hours post-infection it gave 80-85% protection. In vivo: as little as 5% propolis prevented the appearance and development of symptoms of local and i.p. HSV-1 infection in rats and of corneal HSV-1 infection in rabbits. There were no cytotoxic effects at a concentration of 10% in vitro or 20% in vivo. CONCLUSIONS: The potent antiviral activity of propolis against HSV-1 infection in vitro and In vivo is probably due to prevention of virus absorption into the host cells and/or inhibition of an internal step(s) during the viral replication cycle.

PMID: 12455181 [PubMed - indexed for MEDLINE]

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Comment in:

·       Isr Med Assoc J. 2002 Nov;4(11 Suppl):944-6.

The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines.

Barak V, Birkenfeld S, Halperin T, Kalickman I.

Immunology Laboratory for Tumor Diagnosis, Department of Oncology, Hadassah University Hospital, Jerusalem, Israel. barak845@yahoo.com

BACKGROUND: Some herbal remedies are sold as food additives and are believed to have immune-enhancing properties. OBJECTIVES: To study the effect of five herbal remedies--Sambucol Black Elderberry Extract, Sambucol Active Defense Formula and Sambucol for Kids (with known antiviral properties), Protec and Chizukit N (containing propolis and Echinacea, claimed to be immune enhancers)--on the production of cytokines, one of the main components of the immune system. METHODS: The production of four inflammatory cytokines (interleukin-1 beta, tumor necrosis factor alpha, and IL-6 and IL-8) and one anti-inflammatory cytokine (IL-10) was tested using blood-derived monocytes from 12 healthy donors. RESULTS: The Sambucol preparations increased the production of five cytokines (1.3-6.2 fold) compared to the control. Protec induced only a moderate production of IL-8 (1.6 fold) and IL-10 (2.3 fold) while Chizukit N caused only a moderate increase in IL-10 production (1.4 fold). Both Protec and Chizukit N caused moderate decreases in IL-1 beta, TNF alpha and IL-6 production. Lipopolysaccharide, a known activator of monocytes, induced the highest levels of cytokine production (3.6-10.7 fold). CONCLUSIONS: The three Sambucol formulations activate the healthy immune system by increasing inflammatory and anti-inflammatory cytokines production, while the effect of Protec and Chizukit N is much less. Sambucol could therefore have immunostimulatory properties when administered to patients suffering from influenza (as shown before), or immunodepressed cancer or AIDS patients who are receiving chemotherapy or other treatments.

PMID: 12455180 [PubMed - indexed for MEDLINE]

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Egyptian propolis: 2. Chemical composition, antiviral and antimicrobial activities of East Nile Delta propolis.

Abd El Hady FK, Hegazi AG.

Department of Chemistry of Natural Products, National Research Center, Dokki, Giza, Egypt.

Three propolis samples from East Nile Delta, Egypt were collected. Propolis samples were investigated by GC/MS,103 compounds were identified, 20 being new for propolis. Dakahlia propolis was a typical poplar propolis but it contained two new caffeate esters and two new triterpenoids. Ismailia propolis was characterized by the presence of new triterpenic acid methyl esters and it did not contain any aromatic acids, esters and flavonoids. Sharkia propolis was characterized by the presence of caffeate esters only, some di- and triterpenoids. The antiviral (Infectious Bursal Disease Virus and Reo-Virus) and antimicrobial (Staphylococcus aureus; Escherichia coli and Candida albicans) activities of propolis samples were investigated. Dakahlia propolis showed the highest antiviral activity against Infectious Bursal Disease Virus (IBDV) and the highest antibacterial activity against Escherichia coli and the highest antifungal activity against Candida albicans. While Ismailia propolis had the highest antiviral activity against Reo-virus. Sharkia propolis showed the highest antibacterial activity against Staphylococcus aureus and moderate antiviral activity against infectious bursal disease virus and reovirus.

PMID: 12064745 [PubMed - indexed for MEDLINE]

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PM-3, a benzo-gamma-pyran derivative isolated from propolis, inhibits growth of MCF-7 human breast cancer cells.

Luo J, Soh JW, Xing WQ, Mao Y, Matsuno T, Weinstein IB.

Herbert Irving Comprehensive Cancer Center, Columbia Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties. Several components isolated from propolis have been shown to have anticancer activity. This study demonstrates that the compound PM-3 (3-[2-dimethyl-8-(3-methyl-2-butenyl)benzopyran]-6-propenoic acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7 human breast cancer cells. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Treatment of MCF-7 cells with PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein levels of cyclin D1 and cyclin E. PM-3 also inhibited the expression of cyclin D1 at the transcriptional level when examined in cyclin D1 promoter luciferase assays. Induction of apoptosis by PM-3 occurred within 48 hours after treatment of MCF-7 cells. The MCF-7 treated cells also displayed a decrease in the level of the estrogen receptor (ER) protein and inhibition of estrogen response element (ERE) promoter activity. Therefore, PM-3 merits further investigation with respect to breast cancer chemoprevention or therapy.

PMID: 11497245 [PubMed - indexed for MEDLINE]

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A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV).

Vynograd N, Vynograd I, Sosnowski Z.

Institute of Epidemiology, Lvov State Medical University, Ukraine.

Ninety men and women with recurrent genital HSV type 2 participated in a randomized, single-blind, masked investigator, controlled multi-centre study comparing the efficacy of ointment of Canadian propolis containing natural flavonoids with ointments of acyclovir and placebo (vehicle) on healing ability and capacity to remedy symptoms. Thirty individuals were randomized to each group. Treatment was intended to start in the blister phase. All participants had HSV type 2 isolated, confirmed by serum immunoglobulin levels. The participants were examined on the 3rd, 7th and 10th days of treatment by gynaecologists, dermatovenerologists or urologists at seven different medical centres. Apart from clinical symptoms the number and size of the herpetic lesions were noted. At each examination the lesions were classified into four stages: vesicular, ulcerated, crusted and healed. The study ointments were applied to affected areas four times daily. In women with vaginal or cervical lesions a tampon with the appropriate ointment was inserted four times daily for 10 days. Endpoint variables were healing time and time until loss of symptoms. RESULTS: On Day 10, 24 out of 30 individuals in the propolis group had healed. In the acyclovir group 14 out of 30 and in the placebo group 12 out of 30 had healed. (p = 0.0015). The healing process appeared to be faster in the propolis group. In the propolis group 15 individuals had crusted lesions on Day 3 compared to 8 individuals in the acyclovir group and none in the placebo group (p = 0.0006). On Day 7, 10 participants in the propolis group, 4 in the acyclovir group and 3 in the placebo group had healed. At the initial examination all patients had local symptoms and 28% general symptoms. At Day 3, 3 patients in the propolis group had local symptoms compared to 8 and 9 in the acyclovir and placebo groups respectively. Of the women, 66% had vaginal superinfections of microbial pathogens at the initial examination. In the acyclovir and placebo groups no change in the vaginal flora was found following treatment whereas in the propolis group the incidence of superinfection was reduced by 55%. (p = 0.10 n.s.). CONCLUSION: An ointment containing flavonoids appeared to be more effective than both acyclovir and placebo ointments in healing genital herpetic lesions, and in reducing local symptoms.

Publication Types:

·       Clinical Trial

·       Multicenter Study

·       Randomized Controlled Trial

PMID: 10782483 [PubMed - indexed for MEDLINE]

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In vitro antimicrobial activity of propolis and Arnica montana against oral pathogens.

Koo H, Gomes BP, Rosalen PL, Ambrosano GM, Park YK, Cury JA.

School of Dentistry of Piracicaba, State University of Canipinas, Areiao, S.P., Brazil.

Arnica and propolis have been used for thousands of years in folk medicine for several purposes. They possess several biological activities such as anti-inflammatory, antifungal, antiviral and tissue regenerative, among others. Although the antibacterial activity of propolis has already been demonstrated, very few studies have been done on bacteria of clinical relevance in dentistry. Also, the antimicrobial activity of Arnica has not been extensively investigated. Therefore the aim here was to evaluate in vitro the antimicrobial activity, inhibition of adherence of mutans streptococci and inhibition of formation of water-insoluble glucan by Arnica and propolis extracts. Arnica montana (10%, w/v) and propolis (10%, w/v) extracts from Minas Gerais State were compared with controls. Fifteen microorganisms were used as follows: Candida albicans--NTCC 3736, F72; Staphylococcus aureus--ATCC 25923; Enterococcus faecalis--ATCC 29212; Streptococcus sobrinus 6715; Strep. sanguis--ATCC 10556; Strep. cricetus--HS-6; Strep. mutans--Ingbritt 1600; Strep. mutans--OMZ 175; Actinomyces naeslundii--ATCC 12104, W 1053; Act. viscosus OMZ 105; Porphyromonas gingivalis; Porph. endodontalis and Prevotella denticola (the last three were clinical isolates). Antimicrobial activity was determined by the agar diffusion method and the zones of growth inhibition were measured. To assess cell adherence to a glass surface, the organisms were grown for 18 h at 37 degrees C in test-tubes at a 30 degree angle. To assay water-insoluble glucan formation, a mixture of crude glucosyltransferase and 0.125 M sucrose was incubated for 18 h at 37 degrees C in test-tubes at a 30 degree angle. Arnica and propolis extracts (20 microl) were added to these tubes to evaluate the % of inhibition of cell adherence and water-insoluble glucan formation. The propolis extract significantly inhibited all the microorganisms tested (p < 0.05), showing the largest inhibitory zone for Actinomyces spp. The Arnica extract did not demonstrate significant antimicrobial activity. Cell adherence and water-insoluble glucan formation were almost completely inhibited by the propolis extract at a final concentration of 400 microg/ml and 500 microg/ml, respectively. The Arnica extract showed slight inhibition of the adherence of the growing cells (19% for Strep. mutans and 15% for Strep. sobrinus) and of water-insoluble glucan formation (29%) at these same concentrations. Thus, the propolis extract showed in vitro antibacterial activity, inhibition of cell adherence and inhibition of water-insoluble glucan formation, while the Arnica extract was only slightly active in those three conditions.

PMID: 10716618 [PubMed - indexed for MEDLINE]

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Synergism between ethanolic extract of propolis (EEP) and anti-tuberculosis drugs on growth of mycobacteria.

Scheller S, Dworniczak S, Waldemar-Klimmek K, Rajca M, Tomczyk A, Shani J.

Department of Microbiology and Immunology, Silesian Academy of Medicine, Zabrze-Rokitnica, Poland.

Ethanolic extract of propolis exerts a strong anti-bacterial activity, in addition to antifungal, antiviral and antiprotozoal properties. In previous studies from these laboratories we have demonstrated that the intensity of the bactericidal activity of EEP is correlated with the virulence of the mycobacteria tested, and that EEP has a synergistic effect with antibiotics on growth of staphylococcus aureus. In the present study we investigated whether the same synergism and correlation exists between EEP and some anti-tuberculosis drugs on tuberculosis mycobacteria with different degrees of virulence. Six standard strains and 11 wild strains of mycobacteria were exposed for 30 days to EEP, with or without streptomycin, rifamycin, isoniazid or ethambutol. Out of the 17 strains, 8 were resistant to at least two standard antibiotics, and were considered "multi-resistant strains". The rest were either susceptible or resistant to only one of the antimycobacterial drugs. Antagonism was recorded only in one case, when Staphylococcus aureus were treated with a mixture of EEP and ethambutol, suggesting that a chemical bond could have been formed between this anti-tuberculosis antibiotic and one of the active components of the ethanol extract of propolis.

PMID: 10488563 [PubMed - indexed for MEDLINE]

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Apoptosis induced by propolis in human hepatocellular carcinoma cell line.

Choi YH, Lee WY, Nam SY, Choi KC, Park YE.

Department of Pathology, Chun-Chon Sacred Heart Hospital, Hallym University, Chun-Chon city, Kang Won-Do 200-060, Korea.

Propolis has been reported to exhibit a wide spectrum of activities including antibiotic, antiviral, anti-inflammatory, immunostimulatory and tumor carcinostatic properties. We showed propolis induced apoptosis in a human hepatoma cell line (SNU449) by FITC-Annexin V/PI staining. We also compared the apoptosis inducing effect between Korean and Commercial (Sigma # p-1010) propolis. There was no difference on apoptosis between them.

PMID: 10373633 [PubMed - indexed for MEDLINE]

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Antibacterial, antifungal and antiviral activity of propolis of different geographic origin.

Kujumgiev A, Tsvetkova I, Serkedjieva Y, Bankova V, Christov R, Popov S.

Institute of Microbiology, Bulgarian Academy of Sciences, Sofia.

Propolis samples from different geographic origins were investigated for their antibacterial (against Staphylococcus aureus and Escherichia coli), antifungal (against Candida albicans) and antiviral (against Avian influenza virus) activities. All samples were active against the fungal and Gram-positive bacterial test strains, and most showed antiviral activity. The activities of all samples were similar in spite of the differences in their chemical composition. In samples from the temperate zone, flavonoids and esters of phenolic acids are known to be responsible for the above mentioned activities of bee glue; tropical samples did not contain such substances but showed similar activities. Obviously, in different samples, different substance combinations are essential for the biological activity of the bee glue. It seems that propolis has general pharmacological value as a natural mixture and not as a source of new powerful antimicrobial, antifungal and antiviral compounds.

PMID: 10363838 [PubMed - indexed for MEDLINE]

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Correlation between virulence of various strains of mycobacteria and their susceptibility to ethanolic extract of propolis (EEP).

Scheller S, Kawalski H, Oklek K, Dworniczak S, Matsuno T, Waldemar-Klimmek K, Rajca M, Shani J.

Department of Microbiology and Immunology, Silesian Academy of Medicine, Zabrze-Rokitnica, Poland. mikroimm@friko3.onet.pl

Ethanol extract of propolis (EEP) has antibacterial, antiviral, antiprotozoal and antifungal properties, in addition to many biological effects. Our laboratory has demonstrated a synergistic effect of EEP and antibiotics on the growth of Staphylococcus aureus, and suggested that the bactericidal effect of EEP was expressed mainly on virulent mycobacteria rather than on non-virulent (attenuated) ones. The present study was designed to reconfirm the latter finding, by subjecting 17 different mycobacteria strains to EEP, and evaluating whether there is a correlation between the virulence of the mycobacteria strains studied and their susceptibility to EEP. Our findings demonstrate that while the four non-virulent strains studied are not susceptible to EEP, out of the 13 virulent strains studied seven are susceptible and six are resistant to it. These results suggest that while there is no full correlation between virulence of the mycobacteria tested and their susceptibility to EEP, the few strains that were resistant to EEP were non-virulent.

PMID: 9933968 [PubMed - indexed for MEDLINE]

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[Mechanism of the anti-herpetic activity of aqueous extract of propolis. II. Activity of lectins from the aqueous extract of propolis]

[Article in French]

Dumitrescu M, Crisan I, Esanu V.

Institut de Virologie Stefan S. Nicolau, Bucarest, Roumanie.

The report brings proofs of the presence of a lectin in the water propolis extract. It was detected in human fibroblast extracts previously treated with the propolis extract. Presence of the lectin was confirmed by polyacrylamide gel electrophoresis in the presence of SDS.

PMID: 9702248 [PubMed - indexed for MEDLINE]

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Review of the biological properties and toxicity of bee propolis (propolis).

Burdock GA.

Burdock and Associates, Vero Beach, FL 32963, USA.

Propolis is a multifunctional material used by bees in the construction and maintenance of their hives. Use of propolis by humans has a long history, predated only by the discovery of honey. Use of products containing propolis have resulted in extensive dermal contact and it is now increasingly being used a dietary supplement. Unlike many 'natural' remedies, there is a substantive database on the biological activity and toxicity of propolis indicating it may have many antibiotic, antifungal, antiviral and antitumour properties, among other attributes. Although reports of allergic reactions are not uncommon, propolis is relatively non-toxic, with a no-effect level (NOEL) in a 90-mouse study of 1400 mg/kg body weight/day.

PMID: 9651052 [PubMed - indexed for MEDLINE]

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