PROPOLEOS ANTIOXIDANTE

1: Life Sci. 2006 Jan 30; [Epub ahead of print]

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Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and exogenous reactive oxygen species.

Russo A, Troncoso N, Sanchez F, Garbarino JA, Vanella A.

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

Many environmental, physiological and genetic factors have been implicated in defective sperm function, the most common cause of infertility. In addition, sperm preparation techniques such as centrifugation, used prior to in vitro fertilization, are associated with the generation of reactive oxygen species (ROS) and an increase in the level of DNA damage. Factors that can offer spermatozoa protection are, therefore, of great importance. This study was designed to examine in vitro the effect of a Chilean propolis ethanolic extract on human spermatozoa treated with benzo[a]pyrene and exogenous reactive oxygen species. Our experimental evidence demonstrated that the natural drug under investigation is able to protect genomic DNA by damage induced by benzo[a]pyrene, hydrogen peroxide (H(2)O(2)) and hydrogen peroxide in combination with adenosine 5'-diphosphate (ADP) and ferrous sulfate (FeSO(4)), determining a significant reduction of the intracellular oxidants. An increase in membrane damage, measured by monitoring the formation of thiobarbituric acid-reactive substances (TBARS) and lactic dehydrogenase (LDH) release, was observed only in sperm treated with H(2)O(2), ADP and FeSO(4). The propolis extract was shown to possess the capacity to protect sperm membrane from the deleterious action of oxidative attack, reducing TBARS formation and LDH release. In summary, our results evidence that the protective effect exhibited by this natural compound in human spermatozoa is correlated, at least in part, to the antioxidant capacity of its active components, and suggest that propolis may have a role in protection against male infertility.

PMID: 16457855 [PubMed - as supplied by publisher]

2: Life Sci. 2005 Dec 20; [Epub ahead of print]

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Therapeutic effect of paclitaxel and propolis on lipid peroxidation and antioxidant system in 7,12 dimethyl benz(a)anthracene-induced breast cancer in female Sprague Dawley rats.

Padmavathi R, Senthilnathan P, Chodon D, Sakthisekaran D.

Department of Medical Biochemistry, University of Madras, Taramani campus, Chennai-600 113, Tamilnadu, India.

Breast cancer is one of the most common cancers in women of developed and developing countries. The optimum management of which requires a multidisciplinary approach including the use of certain biochemical and molecular markers. The effect of propolis along with paclitaxel on 7,12 dimethyl benz(a)anthracene (DMBA) induced experimental breast cancer was investigated in female Sprague Dawley rats. Female Sprague Dawley rats were divided into five groups of six animals each. Group I served as normal control animal. Group II animals received DMBA (20 mg in 0.5 ml sunflower oil and 0.5 ml of saline) i.p. to develop mammary tumor by the end of 90 days. Group III were breast cancer animals treated with 33 mg paclitaxel/kg body weight (bw) weekly once for 4 weeks. Group IV were breast cancer-bearing animals treated with 50 mg propolis/kg bw for 30 days. Group V were breast cancer-bearing animals treated with both paclitaxel and propolis as mentioned above. Administration of paclitaxel and propolis effectively suppressed breast cancer, which is revealed by the decrease in the extent of lipid peroxidation (LPO) with concomitant increase in the activities of enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) and non-enzymic antioxidants (reduced glutathione (GSH), Vitamin C and Vitamin E) levels when compared to breast cancer-bearing animals treated with either paclitaxel or propolis alone. From our results, we conclude that propolis is a potent antioxidant and, when given in combination with paclitaxel, offers maximum protection against DMBA induced mammary carcinogenesis.

PMID: 16375927 [PubMed - as supplied by publisher]

3: J Agric Food Chem. 2005 Dec 28;53(26):10306-9.

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Suppressive effects of ethanolic extracts from propolis and its main botanical origin on dioxin toxicity.

Park YK, Fukuda I, Ashida H, Nishiumi S, Yoshida K, Daugsch A, Sato HH, Pastore GM.

Department of Food Science, College of Food Engineering, State University of Campinas, P.O. Box 6177, Campinas, SP, Brazil. ykpark@fea.unicamp.br

Suppressive effects of ethanolic extracts prepared from propolis group 12 and its main botanical origin (leaf bud of Baccharis dracunculifolia) on transformation of the aryl hydrocarbon receptor (AhR), the initial action of dioxin toxicity, were investigated. It was found that suppressive effects of propolis on AhR transformation were relatively higher than those of resins of its botanical origin in cell-free system and in Hepa-1c1c7 cells. When the composition of chemical ingredients was measured, propolis contained slightly higher amounts of flavonoid aglycones as compared with its botanical origin with the same characteristics. Moreover, antiradical activity, one of the typical biological activities of flavonoids, in propolis was also slightly higher than that in its botanical origin. These results indicate that not only propolis but also its botanical origin contains high amounts of flavonoid aglycones and that both of them are useful dietary sources for flavonoids with a potency to prevent dioxin toxicity.

PMID: 16366731 [PubMed - indexed for MEDLINE]

4: Toxicol Ind Health. 2005 Oct;21(9):223-30.

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Mobile phone-induced myocardial oxidative stress: protection by a novel antioxidant agent caffeic acid phenethyl ester.

Ozguner F, Altinbas A, Ozaydin M, Dogan A, Vural H, Kisioglu AN, Cesur G, Yildirim NG.

Department of Physiology, School of Medicine, Suleyman Demirel University, Isparta, Turkey. drmfehmi@yahoo.com

Electromagnetic radiation (EMR) or radiofrequency fields of cellular mobile phones may affect biological systems by increasing free radicals, which appear mainly to enhance lipid peroxidation, and by changing the antioxidant defense systems of human tissues, thus leading to oxidative stress. Mobile phones are used in close proximity to the heart, therefore 900 MHz EMR emitting mobile phones may be absorbed by the heart. Caffeic acid phenethyl ester (CAPE), one of the major components of honeybee propolis, was recently found to be a potent free radical scavenger and antioxidant, and is used in folk medicine. The aim of this study was to examine 900 MHz mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and the role of CAPE on myocardial tissue against possible oxidative damage in rats. Thirty rats were used in the study. Animals were randomly grouped as follows: sham-operated control group (N: 10) and experimental groups: (a) group II: 900 MHz EMR exposed group (N: 10); and (b) group III: 900 MHz EMR exposed+CAPE-treated group (N: 10). A 900 MHz EMR radiation was applied to groups II and III 30 min/day, for 10 days using an experimental exposure device. Malondialdehyde (MDA, an index of lipid peroxidation), and nitric oxide (NO, a marker of oxidative stress) were used as markers of oxidative stress-induced heart impairment. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status. In the EMR exposed group, while tissue MDA and NO levels increased, SOD, CAT and GSH-Px activities were reduced. CAPE treatment in group III reversed these effects. In this study, the increased levels of MDA and NO and the decreased levels of myocardial SOD, CAT and GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced heart tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative heart injury. These results show that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative heart impairment in rats.

PMID: 16342473 [PubMed - indexed for MEDLINE]

5: Mol Cell Biochem. 2006 Jan;281(1-2):153-61.

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The protective role of topical propolis on experimental keratitis via nitric oxide levels in rabbits.

Duran N, Koc A, Oksuz H, Tamer C, Akaydin Y, Kozlu T, Celik M.

Department of Microbiology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey.

The aim of this study was to investigate antioxidant, anti-inflammatory, and antibacterial properties of propolis in the treatment of experimental Staphylococcus aureus keratitis. Twenty young New Zealand white rabbits were used in this experiment. Staphylococcus aureus were given by intrastromal injection to 16 rabbits and 4 rabbits were used as control group (Group 1). Group 2 was treated with phosphate-buffered solution drops; Group 3 was administered ethanolic extract of propolis drops; Group 4 received topical ciprofloxacin drops; Group 5 was treated with topical ciprofloxacin drops along with ethanolic extract of propolis drops. The eyes were examined by slit lamp to assess corneal opacity. And then, corneas were removed to determine nitric oxide (NO) levels and count bacteria. Corneas were also evaluated histologically. Corneal NO concentration in gruop 5, treated with a combination of propolis and ciprofloxacin was determined significantly lower (10.0+/- 1.8 mumol/g wet tissue) than in Group 4, treated with ciprofloxacin (24.0+/- 3.1 mumol/g wet tissue), from Group 3, treated with propolis (15.6+/- 1.8 mumol/g wet tissue), and treated with PBS (44.7+/- 7.8 mumol/g wet tissue). There were significantly fewer bacteria in eyes that received propolis plus ciprofloxacin than in eyes treated with ciprofloxacin (p = 0.0001) or propolis (p = 0.0001) or eyes treated with PBS (p = 0.0001). The light microscopic examination revealed that the control group showed normal corneal morphology. In the nontreated group, sections of the stromal infiltration revealed the presence of inflammatory cells, which were diffusely distributed (p < 0.05). Administrations of ciprofloxacin plus propolis resulted in a significantly reduced histological damage with fewer bacterial inoculation of the corneal stroma in comparison with the other groups (p < 0.05). Based on these findings, we suggest that ethanolic extract of propolis has antioxidant, anti-inflammatory, and antibacterial properties for S. aureus keratitis in rabbits.

PMID: 16328968 [PubMed - in process]

6: Mol Cell Biochem. 2006 Jan;282(1-2):83-8.

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Protective effects of melatonin and caffeic acid phenethyl ester against retinal oxidative stress in long-term use of mobile phone: A comparative study.

Ozguner F, Bardak Y, Comlekci S.

Department of Physiology, School of Medicine, Suleyman Demirel University, P. K. 13, Isparta, 32100, Turkey, drmfehmi@yahoo.com.

There are numerous reports on the effects of electromagnetic radiation (EMR) in various cellular systems. Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the efficacy of the protective effects of melatonin and CAPE against retinal oxidative stress due to long-term exposure to 900 MHz EMR emitting mobile phones. Melatonin and CAPE were administered daily for 60 days to the rats prior to their EMR exposure during our study. Nitric oxide (NO, an oxidant product) levels and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of retinal oxidative stress in rats following to use of EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in retinal tissue. Retinal levels of NO and MDA increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of NO and MDA. Likewise, retinal SOD, GSH-Px and CAT activities decreased in EMR exposed animals while melatonin and CAPE caused a significant increase in the activities of these antioxidant enzymes. Treatment of EMR exposed rats with melatonin or CAPE increased the activities of SOD, GSH-Px and CAT to higher levels than those of control rats. In conclusion, melatonin and CAPE reduce retinal oxidative stress after long-term exposure to 900 MHz emitting mobile phone. Nevertheless, there was no statistically significant difference between the efficacies of these two antioxidants against to EMR induced oxidative stress in rat retina. The difference was in only GSH-Px activity in rat retina. Melatonin stimulated the retinal GSH-Px activity more efficiently than CAPE did.

PMID: 16317515 [PubMed - in process]

7: Am J Kidney Dis. 2005 Dec;46(6):e125-9.

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Acute renal failure induced by a Brazilian variety of propolis.

Li YJ, Lin JL, Yang CW, Yu CC.

Department of Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan.

Propolis is a resinous substance collected by honeybees and used in hive construction and maintenance. Cumulative evidence suggests that propolis may have anti-inflammatory, antibiotic, antioxidant, antihepatotoxic, and antitumor properties. In addition to topical applications, products containing propolis have been used increasingly as dietary supplements. Although reports of allergic reactions are not uncommon, propolis is reputed to be relatively nontoxic. Its systemic toxicity is rarely reported and hence may be underestimated. This is the first report of propolis-induced acute renal failure. A 59-year-old man required hemodialysis for acute renal failure. The patient had cholangiocarcinoma and had ingested propolis for 2 weeks before presentation. Renal function improved after propolis withdrawal, deteriorated again after reexposure, and then returned to a normal level after the second propolis withdrawal. This case indicates that propolis can induce acute renal failure and emphasizes the need for vigilance and care when propolis is used as a medicine or dietary supplement.

Publication Types:

·       Case Reports

PMID: 16310564 [PubMed - indexed for MEDLINE]

8: Life Sci. 2005 Nov 19; [Epub ahead of print]

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Caffeic acid phenethyl ester ameliorates cerebral infarction in rats subjected to focal cerebral ischemia.

Tsai SK, Lin MJ, Liao PH, Yang CY, Lin SM, Liu SM, Lin RH, Chih CL, Huang SS.

Department of Anesthesiology, College of Medicine, Buddhist Tzu-Chi University and Hospital, National Taiwan University, Taipei Veterans General Hospital, Taipei, Taiwan.

The effects of caffeic acid phenethyl ester (CAPE), an antioxidant derived from propolis, on the infarct volume elicited by focal cerebral ischemia were studied on Long-Evans rats. Cerebral infarction was induced by microsurgical procedures with ligation of the right middle cerebral artery (MCA) and clipping of bilateral common carotid arteries (CCA) for 60 min. The rats were sacrificed 24 h later and serial brain slices of 2 mm thickness were taken and stained for the measurement of infarct area. CAPE was administered intravenously 15 min before MCA occlusion. Pretreatment of CAPE (0.1, 1 and 10 mug/kg) significantly reduced the total infarct volume from 169.6+/-14.5 mm(3) (control) to 61.0+/-24.1 mm(3) (0.1 mug/kg CAPE), 47.4+/-9.1 mm(3) (1 mug/kg CAPE), and 42.4+/-8.7 mm(3) (10 mug/kg CAPE), respectively. Plasma nitric oxide (NO) content was significantly increased in rats subjected to focal cerebral ischemia. It is concluded that CAPE possesses neuroprotective properties in focal cerebral ischemia injury in rats possibly through its antioxidant effect and/or via the upregulation of NO production.

PMID: 16303144 [PubMed - as supplied by publisher]

9: 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]

10: J Agric Food Chem. 2005 Nov 16;53(23):8957-62.

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Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity of propolis from Tucuman, Argentina.

Nieva Moreno MI, Zampini IC, Ordonez RM, Jaime GS, Vattuone MA, Isla MI.

Instituto de Estudios Vegetales Dr Antonio Rodolfo Sampietro, Facultad de Bioquimica, Quimica y Farmacia, Universidad Nacional de Tucuman, Ayacucho 461, 4000 San Miguel de Tucuman, Argentina.

This study evaluates the toxic, genotoxic/mutagenic, and antimutagenic effects of propolis extract from Amaicha del Valle, Tucuman, Argentina. The cytotoxicity assays carried out with the lethality test of Artemia salina revealed that the LD50 was around 100 microg/mL. Propolis extracts showed no toxicity to Salmonella typhimurium TA98 and TA100 strains and Allium cepa at concentrations that have antibiotic and antioxidant activities. Otherwise, for the testing doses, neither genotoxicity nor mutagenicity was found in any sample. The propolis extracts were able to inhibit the mutagenesis of isoquinoline (IQ) and 4-nitro o-phenylenediamine (NPD) with ID50 values of 40 and 20 microg/plate, respectively. From this result, the studied propolis may be inferred to contain some chemical compounds capable of inhibiting the mutagenicity of direct-acting and indirect-acting mutagens. A compound isolated from Amaicha del Valle propolis, 2',4'-dihydroxychalcone, showed cytotoxic activity (LC50 values of 0.5 microg/mL) but was not genotoxic or mutagenic. Furthermore, this compound was able to inhibit the mutagenicity of IQ (ID50 values of 1 microg/plate) but was unable to inhibit the mutagenicity of NPD. Our results suggest a potential anticarcinogenic activity of Amaicha del Valle propolis and the chalcone isolated from it.

PMID: 16277388 [PubMed - indexed for MEDLINE]

11: Am J Chin Med. 2005;33(5):779-86.

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Protective effect of propolis ethanol extract on ethanol-induced renal toxicity: an in-vivo study.

Liu CF, Lin CH, Lin CC, Lin YH, Chen CF, Lin SC.

National Taipei College of Nursing, Taipei, 112, Taiwan.

Acute p.o. administration of absolute ethanol (10 ml/kg) to fasted mice would produce extensive renal failure. Pretreatment with p.o. administration of propolis ethanol extract (PEE) could prevent such renal failure effectively and dose dependently. This renal protective effect of PEE may be contributed, at least in part, to its antioxidative activity. The maximal antioxidative effect against absolute ethanol (AE)-induced renal failure could be observed 1 hour after PEE administration. In order to further investigate the renal protective mechanism of PEE, lipid peroxidation and superoxide scavenging activity were conducted in vivo. PEE exhibited dose-dependent antioxidative effects on lipid peroxidation in mice renal homogenate. Results indicated that mice with acute renal failure have higher malonic dialdehyde (MDA) levels compared with those in PEE administered mice. It was concluded that the renal protective mechanism of PEE could be contributed, at least in part, to its prominent superoxide scavenging effect; hence, it could protect, indirectly, the kidney from superoxide-induced renal damages.

PMID: 16265990 [PubMed - indexed for MEDLINE]

12: Ann Clin Lab Sci. 2005 Autumn;35(4):440-8.

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In vivo effects of caffeic acid phenethyl ester on myocardial ischemia-reperfusion injury and apoptotic changes in rats.

Cagli K, Bagci C, Gulec M, Cengiz B, Akyol O, Sari I, Cavdar S, Pence S, Dinckan H.

Division of Cardiovascular Surgery, Yuksek Ihtisas Hospital, Ankara, Turkey.

Ischemia/reperfusion (I/R) has been reported to induce apoptotic cellular death in myocardium. This study tested the hypothesis that caffeic acid phenethyl ester (CAPE), one of the active components of propolis, may ameliorate myocardial apoptosis and oxidative myocardial injury. Wistar rats were divided into 4 groups: (i) sham operated, (ii) I/R, (iii) I/R+CAPE, and (iv) I/R+glutathione (GSH). CAPE (10 micromol/kg) was infused iv 10 min before occlusion of the left anterior descending coronary artery (30 min) followed by reperfusion (120 min). GSH (5 mg/kg) was infused iv after the occlusion and immediately before reperfusion. The TdT-mediated in situ nick end-labeling (TUNEL) method was used to evaluate apoptotic activity. I/R resulted in myocardial apoptosis, alterations of antioxidant status, elevation of serum creatine kinase (CK) and aspartate aminotransferase (AST) activities, evidence of lipid peroxidation, and elevated nitric oxide levels, compared to the sham-operation group. No apoptotic cells were found in the myocardial tissue of sham-operated rats. The TUNEL-positive myocardial cells averaged 60%, 30%, and 40% in the I/R, I/R+CAPE, and I/R+GSH groups, respectively. This study demonstrates that pretreatment with CAPE provides cardio-protection from I/R injury. The I/R+CAPE group showed reduced apoptosis, attenuated NO production, elevated myocardial superoxide dismutase (SOD) activity, and diminished serum CK and AST activities, compared to the I/R group.

PMID: 16254262 [PubMed - in process]

13: Cancer Lett. 2005 Oct 15; [Epub ahead of print]

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Dietary artepillin C suppresses the formation of aberrant crypt foci induced by azoxymethane in mouse colon.

Shimizu K, Das SK, Baba M, Matsuura Y, Kanazawa K.

Department of Life Science, Graduate School of Science and Technology, Kobe University, Rokkodai, Nada-ku, Kobe 657-8501, Japan.

Artepillin C, a prenylated phenylpropanoid found specifically in Brazilian propolis, has been shown to be a bioavailable antioxidant. In this study, artepillin C was tested for colon cancer-preventing activity using azoxymethane-challenged ddY mice. Oral doses of 80 and 160mg/kg body weight of propolis or 10mg/kg of artepillin C (equi-amounts to 160mg propolis) reduced significantly the frequency of colonic aberrant crypt foci (ACF) by 39.2, 43.7 and 43.4%, respectively. In liver of the mice, glutathione S-transferase and NADPH:quinone reductase activity increased with the doses of propolis or artepillin C, and an antioxidant-responsive element (ARE) was found to be activated for binding DNA. Artepillin C is considered to suppress the formation of colonic ACF through the activation of ARE and induction of phase II enzymes in liver.

PMID: 16236434 [PubMed - as supplied by publisher]

14: Mol Carcinog. 2005 Dec;44(4):293-9.

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Artepillin C in Brazilian propolis induces G(0)/G(1) arrest via stimulation of Cip1/p21 expression in human colon cancer cells.

Shimizu K, Das SK, Hashimoto T, Sowa Y, Yoshida T, Sakai T, Matsuura Y, Kanazawa K.

Department of Life Science, Graduate School of Science and Technology, Kobe University, Kobe, Japan.

Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis.

PMID: 16224795 [PubMed - indexed for MEDLINE]

15: Biomed Pharmacother. 2005 Dec;59(10):561-70. Epub 2005 Aug 10.

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Antitumor, hematostimulative and radioprotective action of water-soluble derivative of propolis (WSDP).

Orsolic N, Basic I.

Department of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, Croatia. norsolic@yahoo.com

Several studies suggest that dietary supplementation with antioxidant can influence the response to chemotherapy as well as the development of adverse side effects caused by treatment with chemotherapeutic agents. Using CBA mouse model, we investigated a clinically potential use of a water-soluble derivative of propolis (WSDP) in the treatment of various cytopenias induced by radiation and/or chemotherapy. Also, the antimetastatic efficiency of WSDP given intraperitoneally alone or in combination with chemotherapeutic agents and their effects on the blood leukocytes count as well as on hematopoiesis were studied. Tumor was a transplantable mammary carcinoma (MCa) of CBA mouse. Metastases in the lung were generated by injecting viable tumor cells intravenously (iv). WSDP (50 or 150 mg/kg) exerted a significant antimetastatic effect (P < 0.001) when given either before or after tumor cell inoculation. In combined treatment WSDP and Epirubicin profoundly inhibited metastasis formation; this synergistic effect is maximal when Epirubicin and WSDP were administrated after tumor cell inoculation. Positive outcome of combined treatment with WSDP and Epirubicin was also found regarding the number of red and white blood cells in peripheral blood while in mice treated with Epirubicin alone the significant drop in all hematological parameters was noticed on day 13 after tumor cell inoculation. Furthermore, when WSDP (50 mg/kg) was given perorally (po) for 20 consecutive days an increased number of exogenous CFUs was found in treated mice. WSDP given either for 20 or 40 days increased cellularity of hematopoietic tissue and the number of leucocytes in peripheral blood; prolonged treatment with WSDP also elevated myeloid and megakaryocytic types of CFUs. To conclude, these findings indicate that the combination of WSDP with chemotherapeutics could increase the antimetastatic potential of chemotherapeutic agents; these findings suggest the benefits of potential clinical trials using WSDP combined with chemotherapeutic agents in order to maximize their antitumor activity and minimize postchemotherapeutic or radiotherapeutic deteriorated reactions.

PMID: 16202559 [PubMed - indexed for MEDLINE]

16: Mol Cell Biochem. 2005 Sep;277(1-2):109-15.

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Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester.

Oktem F, Ozguner F, Sulak O, Olgar S, Akturk O, Yilmaz HR, Altuntas I.

Department of Pediatric Nephrology, School of Medicine, Suleyman Demirel University, P.K. 13, 32100, Isparta, Turkey. oktemfaruk@hotmail.com

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li2CO3 solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 microM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.

PMID: 16132721 [PubMed - indexed for MEDLINE]

17: Mol Cell Biochem. 2005 Sep;277(1-2):73-80.

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A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Prognostic value of malondialdehyde, N-acetyl-beta-D-glucosaminidase and nitric oxide determination.

Ozguner F, Oktem F, Ayata A, Koyu A, Yilmaz HR.

Department of Physiology, School of Medicine, Suleyman Demirel University, P. K. 13, Isparta, 32100, Turkey. drmfehmi@yahoo.com

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.

PMID: 16132717 [PubMed - indexed for MEDLINE]

18: Mol Cell Biochem. 2005 Aug;276(1-2):31-7.

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Comparative analysis of the protective effects of melatonin and caffeic acid phenethyl ester (CAPE) on mobile phone-induced renal impairment in rat.

Ozguner F, Oktem F, Armagan A, Yilmaz R, Koyu A, Demirel R, Vural H, Uz E.

Department of Physiology, School of Medicine, Suleyman Demirel University, P. K. 13 32100 Isparta, Turkey. drmfehmi@yahoo.com

Melatonin and caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, were recently found to be potent free radical scavengers and antioxidants. There are a number of reports on the effects induced by electromagnetic radiation (EMR) in various cellular systems. Mechanisms of adverse effects of EMR indicate that reactive oxygen species may play a role in the biological effects of this radiation. The present study was carried out to compare the protective effects of melatonin and CAPE against 900 MHz EMR emitted mobile phone-induced renal tubular injury. Melatonin was administered whereas CAPE was given for 10 days before the exposure. Urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in rats exposed to EMR. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Urinary NAG and renal MDA were increased in EMR exposed rats while both melatonin and CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD and GSH-Px activities were decreased in EMR exposed animals while melatonin caused a significant increase in the activities of these antioxidant enzymes but CAPE did not. Melatonin caused a significant decrease in urinary NAG activity and MDA levels which were increased because of EMR exposure. CAPE also reduced elevated MDA levels in EMR exposed renal tissue, but the effect of melatonin was more potent than that of CAPE. Furthermore, treatment of EMR exposed rats with melatonin increased activities of SOD and GSH-Px to higher levels than those of control rats. In conclusion, melatonin and CAPE prevent renal tubular injury by reducing oxidative stress and protect the kidney from oxidative damage induced by 900 MHz mobile phone. Nevertheless, melatonin seems to be a more potent antioxidant compared with CAPE in kidney. (Mol Cell Biochem 276: 31-37, 2005).

PMID: 16132682 [PubMed - indexed for MEDLINE]

19: Clin Biochem. 2005 Oct;38(10):943-7.

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Antiarrhythmic effect of caffeic acid phenethyl ester (CAPE) on myocardial ischemia/reperfusion injury in rats.

Huang SS, Liu SM, Lin SM, Liao PH, Lin RH, Chen YC, Chih CL, Tsai SK.

Department of Pharmacology and Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.

OBJECTIVES: The present study was designed to determine the antiarrhythmic effect of caffeic acid phenethyl ester (CAPE), an active component of propolis, which exhibits antioxidant properties, in rats subjected to myocardial ischemia and ischemia-reperfusion (I/R) injury. DESIGN AND METHODS: Rats were subjected to 30 min coronary artery occlusion for evaluating the effect of CAPE on the myocardial ischemia injury. While in the myocardial I/R injury study, the coronary artery was ligated for a 5-min period of ischemia followed by a 30-min period of reperfusion. Animals were pretreated with or without CAPE before coronary artery ligation and the severity of myocardial ischemia- and I/R-induced arrhythmias and mortality were compared. RESULTS: Pretreatment of CAPE (0.1 and 1 microg/kg) not only reduced both the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) but also decreased the mortality during the myocardial ischemia and I/R injury period. CONCLUSIONS: Our results suggest that CAPE is a potent antiarrhythmic agent with cardioprotective effects in myocardial ischemia and I/R injury rats.

PMID: 16098504 [PubMed - indexed for MEDLINE]

20: Nat Prod Res. 2005 Oct;19(7):673-8.

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Chemical composition of propolis from Canada, its antiradical activity and plant origin.

Christov R, Trusheva B, Popova M, Bankova V, Bertrand M.

Regional Center for Mass Spectrometry, Department of Chemistry, University of Montreal, Quebec, Canada.

The chemical composition of propolis from two regions in Canada was studied: Boreal forest and the Pacific coastal forest that lie outside the area of distribution of Aigeiros poplars, the usual propolis source plants. In the sample from Victoria, p-hydroxyacetophenone, benzyl hydroxybenzoate and cinnamic acid were the major components, accompanied by significant amounts of dihydrochalcones, which allowed the identification of its plant source: Populus trichocarpa of section Tacamahaca. Three dihydrochalcones were new for propolis. The sample from Richmond was characterized by large amounts of p-coumaric and cinnamic acid, typical for poplars of section Leuce, subsection Trepidae, its plant source was identified as P. tremuloides. Both samples showed a good radical scavenging activity against DPPH. Obviously, the Northern type propolis is a promising potential source of biologically active substances and deserves further investigation.

PMID: 16076637 [PubMed - indexed for MEDLINE]

21: 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.