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.

PMID: 16055186 [PubMed - indexed for MEDLINE]


22: Int Immunopharmacol. 2005 Oct;5(11):1652-7.

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Effects of Turkish pollen and propolis extracts on respiratory burst for K-562 cell lines.

Aliyazicioglu Y, Deger O, Ovali E, Barlak Y, Hosver I, Tekelioglu Y, Karahan SC.

Department of Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, 55139, Turkey.

Bee-collected pollen and propolis are apicultural products which are composed of nutritionally valuable substances and contain considerable amounts of polyphenol substances which may act as potent antioxidants. We wanted to show if respiratory burst within a cancer cell lines could be influenced when incubated with pollen and propolis extracts or not. Pollen and propolis extracts at concentrations of 50, 25, 12.5 and 0 mg/ml were prepared by dimethyl sulfoxide (DMSO). K-562 cell cultures and mononuclear cell (MNC) cultures prepared from a peripheral blood sample to serve as control cells were incubated with extracts for 24 h. Determination of respiratory burst was carried out by intracellular dichlorofluorescein (DCFH) test by using flow-cytometric fluorescence analysis. While about 90% and 66% fluorescence was detected at zero concentrations for both K-562 and MNC cultures, fluorescence positivity decreased (between 3.8% and 11.8%) as concentrations of both propolis and pollen extracts increased for K-562 cell culture, but unchanged (between 20% and 83%) for MNC culture. It was concluded that pollen and propolis extracts inhibit respiratory burst within cancer cell lines probably by their antioxidant potentials.

PMID: 16039555 [PubMed - indexed for MEDLINE]


23: Exp Lung Res. 2005 Jun;31(5):483-96.

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Oleic acid-induced lung injury in rats and effects of caffeic acid phenethyl ester.

Koksel O, Kaplan MB, Ozdulger A, Tamer L, Degirmenci U, Cinel L, Basturk M, Kanik A.

Department of Thoracic Surgery, Mersin University, School of Medicine, 33079 Mersin, Turkey. oguzkoksel@mersin.edu.tr

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant and is an active anti-inflammatory component of honeybee propolis. The authors evaluated the effects of CAPE on oxidative stress and lung damage in an oleic acid (OA)-induced lung-injury model. Rats were divided into 5 groups as sham, OA, CAPE, pre-OA-CAPE, and post-OA-CAPE. Acute lung injury was induced by intravenous administration of 100 mg/kg of OA. Pre-OA-CAPE group received CAPE (10 micromol/kg. intravenously) 15 minutes before OA infusion and post-OA-CAPE group received CAPE 2 hours after OA administration. Malondialdehyde (MDA) level of plasma, bronchoalveolar lavage fluid (BALF), and lung tissue; myeloperoxidase activity of BALF and lung tissue; Na(+)-K(+) ATPase activity of lung tissue; and total protein content of BALF were measured. Light microscopic analyses of lung specimens were performed. The increased MDA levels in lung homogenates (47.98+/-13.75 nmol/mL), BALF (31.12+/-3.07 nmol/mL), and plasma (61.84+/-15.34 nmol/mL) decreased significantly to 24.33+/-3.09 nmol/mL (P = 0.000), 23.19+/-4.97 nmol/mL (P = 0.002), and 27.36+/-5.37 nmol/mL (P = 0.000), respectively, following CAPE administration in pre-OA-CAPE group. Another important finding was the restoration of the enzymatic activity of Na(+)-K(+) ATPase from a value of 203.89+/-32.18 nmol Pi/mg Protein/h in OA group, to a value of 302.17+/-51.90 nmol Pi/mg Protein/h (P = 0.012) in pre-OA-CAPE group with CAPE treatment. CAPE has been shown to have a clear attenuating effect on oxidative damage in experimental animal studies. However, further investigations are necessary to suggest CAPE as a treatment agent in critically ill patients with lung injury.

PMID: 16019983 [PubMed - indexed for MEDLINE]


24: Toxicology. 2005 Sep 1;212(2-3):155-64.

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The protective effect of caffeic acid phenethyl ester against cyclosporine A-induced cardiotoxicity in rats.

Rezzani R, Giugno L, Buffoli B, Bonomini F, Bianchi R.

Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy. rezzani@med.unibs.it

Cyclosporine A (CsA) is the immunosuppressor, which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been considered as one of the possible mechanisms of CsA-induced cardiotoxicity. The present investigation examines the ability of caffeic acid phenethyl ester (CAPE), which is an active component of propolis extracts, as a natural antioxidant to protect against CsA-induced oxidative stress and cardiotoxicity. CsA cardiotoxicity was induced by subcutaneous injection of CsA at a dose of 15 mg/kg/body weight daily for 21 days in rats. Cardiotoxicity was evaluated by morphological and biochemical studies. CsA treated rats showed degenerative changes with cardiac fibrosis localized around the fibers. These latters were disorganised and the network was disappeared. The ROS production was increased whereas cytochrome-c-oxidase decreased. The expression and levels of matrix metalloproteinase 2 (MMP2) were increased whereas those of its inhibitor were downregulated. CAPE subcutaneous administration (15 micromol/kg/day) improved cardiac cytoarchitecture, decreased the levels and the expression of MMP2, and increased those of TIMP2 proteins. Moreover, it increased cytochrome-c-oxidase activity and decreased ROS production. These results suggest that CAPE could have protective effect against CsA-induced cardiotoxicity.

PMID: 15967562 [PubMed - indexed for MEDLINE]


25: 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]


26: J Pharm Biomed Anal. 2005 Sep 15;39(3-4):455-62.

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Assessment of the antioxidant activities of Brazilian extracts of propolis alone and in topical pharmaceutical formulations.

Marquele FD, Di Mambro VM, Georgetti SR, Casagrande R, Valim YM, Fonseca MJ.

Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirao Preto-USP, Av. do Cafe s/n 14049, 903 Ribeirao Preto, SP, Brazil. frandm@fcfrp.usp.br

The antioxidant activity of extracts of propolis and of formulations added with these extracts were measured by scavenging different radicals in different systems. For the ethanolic extract of propolis (EEP) and the glycolic extract of propolis (GEP) the IC50 observed were respectively of 0.024 and 0.035 microL/mL in scavenging hydroxyl radical, 0.016 and 0.012 microL/mL in inhibiting lipid peroxidation, 0.22 and 0.24 microL/mL in inhibiting chemiluminescence produced in the H2O2/luminol/horseradish peroxide (HRP) system and about 0.005 microL/mL for both extracts in inhibiting chemiluminescence produced in the xanthine/luminol/xanthine oxidase (XOD) system. The antioxidant activity of extracts of propolis in the formulations was not able to be assessed neither using the deoxyribose assay, since the formulation components interfered in the assay measurements, nor using chemiluminescence in the H2O2/luminol/HRP system, since this method did not show to be sensitive for the extract of propolis evaluation. However, the antioxidant activity of extracts of propolis could be successfully evaluated in the formulations using both lipid peroxidation and chemiluminescence generated in the xanthine/luminol/XOD system inhibitions.

PMID: 15908158 [PubMed - indexed for MEDLINE]


27: 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]


28: Biochem Pharmacol. 2005 Jun 15;69(12):1815-27.

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Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1 expression: involvement of p38 mitogen-activated protein kinase.

Weng MS, Ho YS, Lin JK.

Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 10018, Taiwan.

Flavonoids are a broadly distributed class of plant pigments, universally present in plants. They are strong anti-oxidants that can inhibit carcinogenesis in rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound extracted from many plants, honey, and propolis. It possesses potent anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing cell cycle progression. However, the mechanism by which chrysin inhibits cancer cell growth remains poorly understood. Therefore, we developed an interest in the relationship between MAPK signaling pathways and cell growth inhibition after chrysin treatment in rat C6 glioma cells. Cell viability assay and flow cytometric analysis suggested that chrysin exhibited a dose-dependent and time-dependent ability to block rat C6 glioma cell line cell cycle progression at the G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation in C6 glioma cells exposed to 30 microM chrysin for 24h decreased significantly. We demonstrated the expression of cyclin-dependent kinase inhibitor, p21(Waf1/Cip1), to be significantly increased, but the p53 protein level did not change in chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) kinase activities were reduced by chrysin in a dose-dependent manner. Furthermore, chrysin also inhibited proteasome activity. We further showed that chrysin induced p38-MAPK activation, and using a specific p38-MAPK inhibitor, SB203580, attenuated chrysin-induced p21(Waf1/Cip1) expression. These results suggest that chrysin exerts its growth-inhibitory effects either through activating p38-MAPK leading to the accumulation of p21(Waf1/Cip1) protein or mediating the inhibition of proteasome activity.

PMID: 15869744 [PubMed - indexed for MEDLINE]


29: 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]


30: Biol Pharm Bull. 2005 Apr;28(4):694-700.

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Synergistic antitumor effect of polyphenolic components of water soluble derivative of propolis against Ehrlich ascites tumour.

Orsolic N, Kosalec I, Basic I.

Department of Animal Physiology, Faculty of Science, University of Zagreb, Croatia.

Effect of two preparation (Croatian and Brazilian) of water-soluble derivative of propolis (WSDP), caffeic acid, quercetin, chrysin, naringenin (components present in WSDP) on the development of Ehrlich ascites tumour (EAT) was evaluated. Test components (50 mg/kg) were given perorally or intraperitoneally 2 h prior the intraperitonel injection of EAT (2 x 10(6)) cells. It was observed that all test compounds effectively inhibited tumour growth and the proliferation of EAT. The volume of ascitic fluid induced by EAT cells and total number of cells present in the peritoneal cavity was markedly reduced in EAT-bearing mice treated with test components. In treated mice the number of polymorphonuclear (PMN) cells in the peritoneal cavity was increased while the number of macrophages was decreased. The macrophage spreading activity revealed that WSDP and all test compounds affected the functional state of macrophages increasing their tumorcidal activity; the effect of WSDP was most pronounced indicating synergistic effect of components present in WSDP. Antitumor activity of WSDP may be the result of different specific mechanism(s) of flavonoids present as compared to individual flavonoid given alone. It is likely that the part of antitumor efficacy of test components against EAT cells was the results of increased activity of macrophages.

PMID: 15802812 [PubMed - indexed for MEDLINE]


31: Acta Med Croatica. 2004;58(5):373-6.

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[Antioxidative activity of propolis from Dalmatia (Croatia)]

[Article in Croatian]

Katalinic V, Radic S, Ropac D, Mulic R, Katalinic A.

Odjel sanitarne kemije i toksikologije, Institut pomorske medicine HRM, Split, Hrvatska.

AIM: The aim of this study was to determine the antioxidative activity of propolis from ecologically clean parts of Dalmatia. METHODS: Phenol concentration in ethanolic propolis extracts was determined by Folin-Ciocalteu reagent using gallic acid as the standard. Flavonoid phenolic compounds were analyzed after precipitation with formaldehyde. The residual non-flavonoid phenolics were also determined by Folin-Ciocalteu method. By determining the change of peroxide number (PN), of tiobarbiture acid reactive species (TBARS), and of DPPH-radical activity, antioxidative efficiency of propolis was tested and compared with well known and widely used synthetic antioxidants. Values of PN and TBARS were determined at 60 degrees C in samples of trigyceride substrate (lard) without and with the addition of antioxidants. Compared was the efficiency of three antioxidants: propolis (alcoholic extract), vitamin E, and (+)-catechin in a concentration of 1%. PN was monitored during 50 days. By the method of Sedlacek, TBARS were measured during 30 days. Antioxidative activity of propolis extract was also measured in terms of hydrogen donating ability using stable radical alpha,alpha-diphenyl-beta-picril hidrazyl (DPPH*) and compared with commercial synthetic antioxidants of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and (+)-cathecin. Inhibition degree of DPPH* was calculated by the formula of Yen and Duh. RESULTS: Total phenol content, expressed as gallic acid, in propolis extracts varied from 75.2 to 90.2 g/kg propolis. The proportion of flavonoids in total phenols ranged from 62% to 65%. Values of TBARS were not increased only in samples with added propolis. The inhibition of DPPH-radical by propolis extracts ranged from 93% to 96%, by catechin 95%, by BHT 49%, and by BHA 64%. Compared to BHT and BHA, propolis extracts showed greater reducing activity against DPPH-radical. DISCUSSION: The chemical composition of propolis, and thus its biological activity depend on the plant from which it has been collected, and on the macro- and microclimatic conditions. Many compounds in propolis exert antioxidative activity. A belief was expressed that the biological activity of propolis is very probably based mostly on its antioxidative efficiency. Dalmatian propolis showed high efficiency in the prevention of oxidative processes. This could be explained by the high proportion of polyphenol constituents, especially flavonoids. A very low and equal degree of increase of PN, as a measure of oxidative processes, was noticed in the samples of triglyceride substrate with the addition of propolis and (+)-catechin. The greatest rise of TBARS was measured in the samples of pure lard. There was no increase of TBARS only in the samples with added propolis. Propolis and (+)-catechin showed great efficiency in the inhibition of DPPH-radical, greater than BHT and BHA, which are widely used in food industry. CONCLUSION: The results indicate that Dalmatian propolis could be an efficient protective agent against oxidative processes in food. The high antioxidative activity of propolis, its natural origin, and present knowledge about its biological properties, make it a very promising nutritional additive for human diet.

PMID: 15756802 [PubMed - indexed for MEDLINE]


32: Yakugaku Zasshi. 2005 Mar;125(3):315-21.

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[Xanthine oxidase inhibitory activity and hypouricemia effect of propolis in rats]

[Article in Japanese]

Yoshizumi K, Nishioka N, Tsuji T.

Fancl Corporation Central Research Laboratory, Yokohama 244-0806, Japan. kayoshizu@fancl.co.jp

The xanthine oxidase (XOD) inhibitory activity of propolis from China and Brazil was measured. The propolis from both place were seen to have XOD inhibitory activity. However, a stronger tendency was shown in the propolis from China. The compounds in each the propolis were measured quantitatively. A great deal of chrysin, galangin, and caffeic acid phenetyl ester were found in the propolis from China, an abundance of p-coumaric acid and artepillin C in the propolis from Brazil. Therefore it was revealed that the propolis compounds are very different depending on their place of origin. The XOD inhibitory activity of these five compounds was measured. Caffeic acid phenetyl ester had the strongest activity, with chrysin and galangin next; p-coumaric acid and artepillin C showed weak XOD inhibitory activity. We evaluated the hypouricemic effect of propolis from China on hyperuricemia induced by the uricase inhibitor, oxonic acid (500 mg/kg p.o., 1 h before the test drugs), and measured plasma uric acid values in rats. Oral propolis had a hypouricemic effect 2 h after its administration to oxonate-pretreated rats. These results suggested that a continuous intake of propolis may be effective for the prevention and the treatment of gout and hyperuricemia.

PMID: 15738631 [PubMed - indexed for MEDLINE]


33: J Ethnopharmacol. 2005 Feb 28;97(2):273-80. Epub 2005 Jan 12.

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Caffeic acid phenethyl ester protects kidneys against carbon tetrachloride toxicity in rats.

Ogeturk M, Kus I, Colakoglu N, Zararsiz I, Ilhan N, Sarsilmaz M.

Department of Anatomy, Faculty of Medicine, Firat University, 23119 Elazig, Turkey.

Caffeic acid phenethyl ester (CAPE), an active component of propolis produced by honeybees, exhibits antioxidant and anti-inflammatory properties. The aim of this study was to investigate possible protective effects of CAPE on carbon tetrachloride (CCl4)-induced renal damage in rats. A total of 24 animals were divided into three equal groups: the control rats received pure olive oil subcutaneously, rats in the second group were injected with CCl4 (0.5 ml/kg, s.c. in olive oil) and rats in the third group were injected with CCl4 (0.5 ml/kg) plus CAPE (10 micromol/kg, i.p.) every other day for one month. At the end of the experimental period, the animals were sacrificed and blood samples were collected. Serum urea and creatinine levels and renal malondialdehyde (MDA) contents were determined. Histopathological examination of the kidney was also performed using light microscopic methods. It was found that kidney MDA levels were increased significantly following CCl4 exposure and this increase was significantly inhibited by CAPE treatment, while no significant changes were observed in serum urea and creatinine levels. CCl4 administration alone also caused histopathologically prominent damage in the kidney compared to the control group. Glomerular and tubular degeneration, interstitial mononuclear cell infiltration and fibrosis, and vascular congestion in the peritubular blood vessels were observed in the renal cortex. With exception of rare vascular congestions, these histopathological changes were disappeared in rats treated with CCl4 plus CAPE. In view of the present findings, it is suggested that CAPE protects kidneys against CCl4 toxicity.

PMID: 15707765 [PubMed - indexed for MEDLINE]


34: 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]


35: 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]


36: Fitoterapia. 2004 Dec;75(7-8):683-9.

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New polyisoprenylated benzophenones from Venezuelan propolis.

Trusheva B, Popova M, Naydenski H, Tsvetkova I, Gregorio Rodriguez J, Bankova V.

Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

Two new polyisoprenylated benzophenones, 18-ethyloxy-17-hydroxy-17,18-dihydroscrobiculatone A and 18-ethyloxy-17-hydroxy-17,18-dihydroscrobiculatone B, together with the known scrobiculatones A and B, were isolated from Venezuelan propolis. The scrobiculatones A and B showed significant antibacterial activity and moderate toxicity to Artemia salina nauplii.

PMID: 15567244 [PubMed - indexed for MEDLINE]


37: J Agric Food Chem. 2004 Dec 1;52(24):7286-92.

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Antioxidant activity and constituents of propolis collected in various areas of Korea.

Ahn MR, Kumazawa S, Hamasaka T, Bang KS, Nakayama T.

Laboratory of Functional Food Science and COE Program in the 21st Century, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.

Propolis is a resinous substance collected by honeybees from various plant sources. The composition of propolis depends on time, vegetation, and the area of collection. This study examined the antioxidant activity of propolis from various areas of Korea: Chilgok, Cheongju, Geochang, Muju, Pocheon, and Sangju. Ethanol extracts of propolis (EEP) were prepared and evaluated for their antioxidant activity by beta-carotene bleaching, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assays. Furthermore, the major constituents in EEP were identified by high-performance liquid chromatography analysis with a photodiode array and mass spectrometric detection, and each component was quantitatively analyzed. EEP from Cheongju and Muju had relatively strong antioxidant activity accompanied by high total polyphenol contents. Propolis from Cheongju contained large amounts of antioxidative compounds, such as caffeic acid, kaempferol, and phenethyl caffeate. On the other hand, propolis from Pocheon had compounds not seen in propolis from other areas.

PMID: 15563208 [PubMed - indexed for MEDLINE]


38: Life Sci. 2004 Dec 17;76(5):545-58.

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Chilean propolis: antioxidant activity and antiproliferative action in human tumor cell lines.

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

Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, v.le A. Doria 6, 95125 Catania-Italy. alrusso@unict.it

Propolis, a natural product derived from plant resins collected by honeybees, has been used for thousands of years in traditional medicine all over the world. The composition of the propolis depends upon the vegetation of the area from where it was collected and on the bee species. In this study, we investigated the antioxidant activity of a propolis sample, provided by NATURANDES-CHILE, collected in a temperate region of central Chile. In addition, this natural compound was tested for its antiproliferative capacity on KB (human mouth epidermoid carcinoma cells), Caco-2 (colon adenocarcinoma cells) and DU-145 (androgen-insensitive prostate cancer cells) human tumor cell lines. Results showed that this Chilean propolis sample exhibits interesting biological properties, correlated with its chemical composition and expressed by its capacity to scavenge free radicals and to inhibit tumor cell growth.

PMID: 15556167 [PubMed - indexed for MEDLINE]


39: Yakugaku Zasshi. 2004 Nov;124(11):847-50.

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[Assessment of antioxidant activity of natural compound by water- and lipid-soluble antioxidant factor]

[Article in Japanese]

Usami E, Kusano G, Katayose T, Wachi H, Seyama Y.

Chigasaki Municipal Hospital, Chigasaki 253-0042, Japan. kusuri@mqi.biglobe.ne.jp

We evaluated the antioxidant activity of natural compounds in water-soluble and lipid-soluble phases and found that ferulic acid, quercetin and caffeic acid showed stronger activity in the water-soluble phase. Various fractions isolated from Bidens pilosa showed this activity mainly in the water-soluble phase. Antioxidant activity in the lipid-soluble phase of propolis depended on the lipophilic extraction.

PMID: 15516812 [PubMed - indexed for MEDLINE]


40: Indian J Exp Biol. 2004 Oct;42(10):993-7.

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Effect of propolis extract on acute carbon tetrachloride induced hepatotoxicity.

Shukla S, Bhadauria M, Jadon A.

School of Studies in Zoology, Jiwaji University, Gwalior, India. dr_sshukla@hotmail.com

Ethanolic extract of propolis was administered to rats intoxicated by carbon tetrachloride. Administration of bolus dose of CCl4 (1.5 ml/kg, ip) resulted in elevation of serum transaminases and serum alkaline phosphatase activities. Levels of hepatic lipid peroxidation were significantly increased. On the contrary, there was significant decrease in hepatic reduced glutathione level. The propolis extract (100 and 200 mg/kg, po) exhibited recoupment in both pre- and post-treatment (prophylactic and curative studies) of biochemical changes induced by CCl4. The post treatment of 200 mg/kg, po extract showed most significant hepatoprotective effect. Histopathological studies showed damage in hepatocytes and disturbed chord arrangement after toxicant administration. Propolis extract (200 mg/kg, po) was found to be more effective in restoring CCl4 induced histopathological alterations.

PMID: 15511003 [PubMed - indexed for MEDLINE]


41: Oncol Res. 2004;14(9):415-26.

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Resveratrol and propolis as necrosis or apoptosis inducers in human prostate carcinoma cells.

Scifo C, Cardile V, Russo A, Consoli R, Vancheri C, Capasso F, Vanella A, Renis M.

Department of Biological Chemistry, Medicinal Chemistry and Molecular Biology, University of Catania, Viale Andrea Doria, 6, 95125 Catania, Italy.

Vegetables and fruit help the prevention and the therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects of resveratrol (100 and 200 microM), a phytoalexin found in grapes, and of the ethanolic extract of propolis (50 and 100 microg/ml), a natural honeybee hive product, were tested in androgen-resistant prostate cancer cells (DU145), a cell line resembling the last stage of prostate carcinoma. A comparison between the activity of these micronutrients and vinorelbine bitartrate (Navelbine), a semi-synthetic drug normally used in the therapy of prostate cancer, was conducted. Several biochemical parameters were tested, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), cell redox status (nitric oxide formation, reactive oxygen species production, reduced glutathione levels), genomic DNA fragmentation (COMET assay) with special attention on the presence of apoptotic DNA damage (TUNEL test), and possible mitochondrial transmembrane potential alteration (deltapsi). Our results point out the anticancer activity of resveratrol and propolis extract in human prostate cancer, exerting their cytotoxicity through two different types of cell death: necrosis and apoptosis, respectively. The data obtained suggest the possible use of these micronutrients both in alternative to classic chemotherapy, and in combination with very low dosage of vinorelbine (5 microM).

PMID: 15490973 [PubMed - indexed for MEDLINE]


42: Evid Based Complement Alternat Med. 2004 Sep 1;1(2):175-185.

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Comparison of Radical Scavenging Activity, Cytotoxic Effects and Apoptosis Induction in Human Melanoma Cells by Taiwanese Propolis from Different Sources.

Chen CN, Weng MS, Wu CL, Lin JK.

Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Section 1, Jen-Ai Road, Taipei 100, Taiwan.

Propolis is a sticky substance that is collected from plants by honeybees. We previously demonstrated that propolins A, B, C, D, E and F, isolated from Taiwanese propolis (TP), could effectively induce human melanoma cell apoptosis and were strong antioxidant agents. In this study, we evaluated TP for free radical scavenging activity by DPPH (1,2-diphenyl-2-picrylhydrazyl). The phenolic concentrations were quantified by the Folin-Ciocalteu method. The apoptosis trigger activity in human melanoma cells was evaluated. TP contained a higher level of phenolic compounds and showed strong capability to scavenge free radicals. Additionally, TP1g, TP3, TP4 and TP7 exhibited a cytotoxic effect on human melanoma cells, with an IC(50) of approximately 2.3, 2.0, 3.3 and 3.3 mug/ml, respectively. Flow cytometric analysis for DNA fragmentation indicated that TP1g, TP2, TP3 and TP7 could induce apoptosis in human melanoma cells and there is a marked loss of cells from the G2/M phase of the cell cycle. To address the mechanism of the apoptosis effect of TP, we evaluated its effects on induction of apoptosis-related proteins in human melanoma cells. The levels of procaspase-3 and PARP [poly(ADP-ribose) polymerase] were markedly decreased. Furthermore, propolins A, B, C, D, E and F in TP were determined using HPLC. The results indicate that TP is a rich source of these compounds. The findings suggest that TP induces apoptosis in human melanoma cells due to its high level of propolins.

PMID: 15480443 [PubMed - as supplied by publisher]


43: Cell Biochem Funct. 2004 Sep-Oct;22(5):287-90.

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The effects of the caffeic acid phenethyl ester (CAPE) on erythrocyte membrane damage after hind limb ischaemia-reperfusion.

Tamer L, Sucu N, Ercan B, Unlu A, Calikoglu M, Bilgin R, Degirmenci U, Atik U.

Department of Biochemistry, Medical Faculty, Mersin University, 33079 Mersin, Turkey. lutamer@yahoo.com

Reactive oxygen species have been implicated in pathogenesis injury after ischaemia-reperfusion (I/R). Caffeic Acid Phenethyl Ester (CAPE), an active component of honeybee propolis extract, exhibits antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of CAPE on erythrocyte membrane damage after hind limb I/R. Rats were divided into two groups: I/R and I/R with CAPE pre-treatment. They were anaesthetized with intramuscular ketamine 100 mg kg(-1). A 4-h I/R period was performed on the right hind limb of all animals. In the CAPE-treated group, animals received CAPE 10 microm by intraperitoneal injection 1 h before the reperfusion. At the end of the reperfusion period, a midsternotomy was performed. A 5-ml blood sample was withdrawn from the ascending aorta for biochemical assays. Serum and erythrocyte membrane MDA levels were significantly lower in the CAPE-treated group when compared to the I/R group ( p = 0.001 and p<0.001, respectively). Erythrocyte membrane Na(+)-K(+) ATPases activity in the CAPE-treated group was significantly higher than the I/R group ( p<0.001). In conclusion, CAPE seems to be effective in protecting against oxidative stress. Therefore, we suggest that in order to decrease I/R injury, pre-administration of CAPE may be a promising agent for a variety of conditions associated with I/R.

PMID: 15338467 [PubMed - indexed for MEDLINE]


44: J Chemother. 2004 Aug;16(4):381-7.

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Caffeic acid phenethyl ester ameliorated ototoxicity induced by cisplatin in rats.

Kizilay A, Kalcioglu MT, Ozerol E, Iraz M, Gulec M, Akyol O, Ozturan O.

Department of Otorhinolaryngology, Inonu University Medical School, Malatya, Turkey. akizilay@inonu.edu.tr

Caffeic acid phenethyl ester (CAPE), an active component of propolis, exhibits antioxidant properties. This experimental study was designed to determine the effect of CAPE on ototoxicity induced with cisplatin. Twenty-four adult Wistar albino rats were divided into four groups: cisplatin (n=6), saline (n=6), CAPE (n=6), and cisplatin plus CAPE (n=6). Rats were tested before and 5 days after cisplatin treatment with or without chemo protection. The Distortion Product Otoacoustic Emissions (DPOAEs) were elicited from the control and experimental animals utilizing the standard commercial Otoacoustic Emission (OAEs) apparatus. The animals in all groups were sacrificed under general anesthesia on the fifth day following last OAE measurements. For biochemical investigations, the blood samples were drawn from inferior vena cava. On day 0, the initial baseline DPOAEs measurement results presented similar values while comparing the groups in drug free phase (p>0.05). On day 5, intrasubject measurement parameters of DPgrams and I/O functions of cisplatin group were significantly deteriorated (p<0.05). The second measurements of the other groups revealed no significant differences between their DPgrams and I/O functions in all frequencies (p>0.05). Among the biochemical parameters, plasma xanthine oxidase (XO) activity was found to be more elevated in the cisplatin group than the saline group (p<0.05). CAPE led to more decreased XO activity than cisplatin (p<0.05). The results of this study show that prophylactic administration of CAPE for cisplatin ototoxicity ameliorated hearing deterioration in rats.

PMID: 15332714 [PubMed - indexed for MEDLINE]


45: Clin Biochem. 2004 Aug;37(8):702-5.

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Reduction of ischemia--reperfusion induced myocardial infarct size in rats by caffeic acid phenethyl ester (CAPE).

Ozer MK, Parlakpinar H, Acet A.

Department of Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey. mkozer1971@yahoo.com

Myocardial ischemia--reperfusion (MI/R) represents a clinically relevant problem associated with thrombolysis, angioplasty, and coronary bypass surgery. MI/R injury is known to occur on restoration of coronary flow after a period of myocardial ischemia. Injury of myocardium caused by I/R includes cardiac contractile dysfunction, arrhythmias, as well as irreversible myocyte damage. Prevention of myocardial death in acute coronary syndromes is the immediate goal of therapy. The main factor concerned with the experimental generation of reperfusion damage is oxygen-derived free radicals. This MI/R injury has been shown to be salvaged by supplementing antioxidants to diseased hearts. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has antioxidant and anti-inflammatory properties, and may function in cardiac protection against I/R-induced damage. To test this hypothesis, we randomly assigned 14 male Wistar rats for necrosis experiments. To produce myocardial necrosis, the left main coronary artery was occluded for 30 min, followed by 120 min of reperfusion in anesthetized rats. CAPE (50 microM kg-1) was given intravenously 10 min before occlusion and continued during ischemia by infusion pump. The volume of infarct and the risk zone was determined by planimentry of each tracing and multiplying by the slice thickness. Infarct was normalized by expressing it as a percentage of the area at risk. Compared to control group, CAPE administration statistically reduced the myocardial infarct size/area of risk zone (50 +/- 4% and 32 +/- 6%, respectively) and the myocardial infarct size (23 +/- 3% and 9 +/- 4%, respectively) in rat model of ischemia-reperfusion. In conclusion, this result shows that CAPE is important in reducing I/R-induced myocardial damage.

PMID: 15302615 [PubMed - indexed for MEDLINE]


46: Nahrung. 2004 Jun;48(3):226-9.

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Preparation and functional properties of extracts from bee bread.

Nagai T, Nagashima T, Myoda T, Inoue R.

Department of Food Science and Technology, Tokyo University of Agriculture, Hokkaido 0992493, Japan. t1nagai@seibutu.bioindustry.nodai.ac.jp

Three extracts, namely hot-water fraction (HWF), water-soluble fraction (WSF), and ethanol-soluble fraction (ESF), were prepared from fresh bee bread imported from Lithuania. The protein and total phenolic contents of these samples were very high. Among them, WSF at 100% concentration showed the highest antioxidative ability and scavenging ability. On the other hand, ESF at 10% concentration possessed the highest ability against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. Bee bread will apply more and more as health food and medicine due to its functional properties such as antioxidative ability and scavenging activities of reactive oxygen species.

PMID: 15285117 [PubMed - indexed for MEDLINE]


47: Free Radic Biol Med. 2004 Aug 1;37(3):386-94.

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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]


48: Arch Biochem Biophys. 2004 Apr 15;424(2):181-8.

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Antioxidative bioavailability of artepillin C in Brazilian propolis.

Shimizu K, Ashida H, Matsuura Y, Kanazawa K.

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

Propolis has strong antioxidative activity. We investigated here whether this activity was available in intestinal Caco-2 and hepatic HepG2 cells. Phenolics in Brazilian propolis, extracted with ethyl acetate after the removal of resin and wax with 90% methanol, included artepillin C at 21 mmol/100 g, p-coumaric acid and cinnamic acid relatives 24mmol, kaempferol and its derivatives 9.4 mmol, naringenin 2.8 mmol, isosakuranetin 0.9 mmol, chrysin at 0.8 mmol/100 g, and several minor components. When the extract was added to the apical side of Caco-2 monolayers, artepillin C was specifically incorporated into the cells and released to the basolateral side mostly without conjugation. Then, artepillin C was added to HepG2 cells and exposed to reactive oxygens. Artepillin C prevented oxidative damage dose-dependently, and suppressed lipid peroxidation evaluated with thiobarbituric acid reactive substances by 16% and the formation of 8-hydroxy-2'-deoxyguanosine in DNA by 36% at a concentration of 20microM. Artepillin C is a bioavailable antioxidant.

PMID: 15047190 [PubMed - indexed for MEDLINE]


49: J Biol Chem. 2004 Jun 25;279(26):26885-92. Epub 2004 Mar 23.

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Stimulatory actions of caffeic acid phenethyl ester, a known inhibitor of NF-kappaB activation, on Ca2+-activated K+ current in pituitary GH3 cells.

Lin MW, Yang SR, Huang MH, Wu SN.

Institute of Basic Medical Sciences, National Cheng-Kung University Medical College, Tainan 701, Taiwan.

Caffeic acid phenethyl ester (CAPE), a phenolic antioxidant derived from the propolis of honeybee hives, is known to be an inhibitor of activation of nuclear transcript factor NF-kappaB. Its effects on ion currents have been investigated in pituitary GH(3) cells. This compound increased Ca(2+)-activated K(+) current (I(K(Ca))) in a concentration-dependent manner with an EC(50) value of 14 +/- 2 microm. However, the magnitude of CAPE-induced stimulation of I(K(Ca)) was attenuated in GH(3) cells preincubated with 2,2'-azo-bis-(2-amidinopropane) hydrochloride (100 microm) or t-butyl hydroperoxide (1 mm). CAPE (50 microm) slightly suppressed voltage-dependent L-type Ca(2+) current. In inside-out configuration, CAPE (20 microm) applied to the intracellular face of the detached patch enhanced the activity of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels with no modification in single-channel conductance. After BK(Ca) channel activity was increased by CAPE (20 microm), subsequent application of nordihydroguaiaretic acid (20 microm) did not further increase the channel activity. CAPE-stimulated channel activity was dependent on membrane potential. CAPE could also increase Ca(2+) sensitivity of BK(Ca) channels in these cells. Its increase in the open probability could primarily involve a decrease in the mean closed time. In current-clamp conditions, CAPE hyperpolarized the membrane potential and reduced the firing of action potentials. The stimulatory effects on these channels may partly contribute to the underlying mechanisms through which this compound influences the functional activities of neurons or neuroendocrine cells. Caution has to be used in attributing its response in the activation of NF-kappaB.

PMID: 15039450 [PubMed - indexed for MEDLINE]


50: Toxicology. 2004 Mar 1;196(1-2):87-93.

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Antioxidative natural product protect against econazole-induced liver injuries.

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

National Taipei College of Nursing, Taipei 112, Taiwan.

The study objective of this research is in order to investigate the hepatoprotective and therapeutic effects of propolis ethanol extract (PEE) on acute econazole-induced liver injury. Positive control of various concentrations of PEE on liver function and the dose-response relationship of liver injury induced by various doses of econazole were firstly observed from biochemical assay of serum level of aspartate transaminase (SGOT) and serum alanine transaminase (SGPT) and histopathological microscopic examination. The hepatoprotective effects of various concentration of PEE on liver damage induced by hepatotoxic dose (300 mg/kg) of econazole were observed by the obvious decrement of SGOT and SGPT level and further confirmed by hepatohistological microscopic examination. The inhibitory effects of PEE on FeCl(2)-induced (in vitro) or econazole-induced (in vivo) lipid peroxidation were investigated from the measurement of the formed malonic dialdehyde (MDA) level in the rat liver homogenate. The IC(50) (microM) of various concentrations of PEE in the superoxide scavenging activity in econazole (300 mg/kg)-damaged rat liver homogenate were assessed by cytochrome c reduction method and compared with that of (+)-alpha-tocopherol. It could be postulated that the hepatoprotective effect of PEE may be, at least in part, due to their inhibitory ability on membrane lipid peroxidation and free radical formation or due to their free radical scavenging ability.

PMID: 15036759 [PubMed - indexed for MEDLINE]


51: Burns. 2004 Mar;30(2):121-5.

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The effect of CAPE on lipid peroxidation and nitric oxide levels in the plasma of rats following thermal injury.

Hosnuter M, Gurel A, Babuccu O, Armutcu F, Kargi E, Isikdemir A.

Department of Plastic and Reconstructive Surgery, Zonguldak Karaelmas University School of Medicine, Kozlu-Zonguldak 67600, Turkey. hosnuter@karaelmas.edu.tr

Both experimental and clinical studies have shown that oxygen-derived free radicals rise in the plasma after thermal injury and participate in the pathogenesis of tissue damage. Hence, various antioxidant molecules have been used in treatment of burn injury both experimentally and clinically. Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have potent antioxidant property. The purpose of the present study was to investigate the effects of CAPE on oxidative stress in plasma of burned rats. Experiment was designed in three groups of rats with 20% full-thickness burn: (a) sham burn (n = 7); (b) burn only (n = 22); (c) burn + treatment with CAPE (n = 22). Plasma levels of malondialdehyde (MDA), nitric oxide (NO) and the activities of xanthine oxidase (XO), and superoxide dismutase (SOD) were used as both bio-indicators of oxidant status and determinant of antioxidant effect of CAPE. They were assessed by biochemical methods at 1st, 3rd, 7th, and 14th post-burn days. In conclusion, CAPE was shown to possess antioxidant activity by saving SOD activity, preventing XO activity and decreasing the levels of MDA, and NO. Our study showed that CAPE may be beneficial in burn injury.

PMID: 15019118 [PubMed - indexed for MEDLINE]


52: Arch Pediatr Adolesc Med. 2004 Mar;158(3):222-4.

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Comment on:

       Arch Pediatr Adolesc Med. 2004 Mar;158(3):217-21.


Can an herbal preparation of echinacea, propolis, and vitamin C reduce respiratory illnesses in children?

Sangvai S, Chianese J, Morone N, Bogen DL, Voigt L, Shaikh N.

General Academic Pediatrics, Children's Hospital of Pittsburgh, PA 15213, USA. shilpa.sangvai@chp.edu

Publication Types:

       Comment


PMID: 14993079 [PubMed - indexed for MEDLINE]


53: Arch Pediatr Adolesc Med. 2004 Mar;158(3):217-21.

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Comment in:

       Arch Pediatr Adolesc Med. 2004 Mar;158(3):222-4.


Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study.

Cohen HA, Varsano I, Kahan E, Sarrell EM, Uziel Y.

Pediatric and Adolescent Ambulatory Community Clinic, Petach Tikva, Israel. hermanc@post.tau.ac.il

OBJECTIVE: To evaluate the effectiveness and safety of a preparation containing echinacea, propolis, and vitamin C in the prevention of respiratory tract infections in children during a 12-week winter period. DESIGN: Randomized, double-blind, placebo-controlled study. SUBJECTS: Four hundred thirty children, aged 1 to 5 years, were randomized to an herbal extract preparation (n = 215) or a placebo elixir (n = 215). INTERVENTION: Administration of an herbal preparation (Chizukit) containing 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C, or placebo (5.0 mL and 7.5 mL twice daily for ages 1 to 3 years and 4 to 5 years, respectively) for 12 weeks. RESULTS: Significant mean +/- SD reductions of illnesses were seen in the Chizukit group in the number of illness episodes, 138 vs 308 (55% reduction); number of episodes per child, 0.9 +/- 1.1 vs 1.8 +/- 1.3 (50% reduction, P<.001); and number of days with fever per child, 2.1 +/- 2.9 vs 5.4 +/- 4.4) (62% reduction, P<.001). The total number of illness days and duration of individual episodes were also significantly lower in the Chizukit group. Adverse drug reactions were rare, mild, and transient. CONCLUSION: A preventive effect of a product containing echinacea, propolis, and vitamin C on the incidence of respiratory tract infections was observed.

Publication Types:

       Clinical Trial

       Multicenter Study

       Randomized Controlled Trial


PMID: 14993078 [PubMed - indexed for MEDLINE]


54: Bioresour Technol. 2004 May;93(1):43-8.

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Screening of poplar biomass for bio-active compounds: a simple method to assess antioxidant activity.

Warnant P, Mertens P, Marche C.

ISI, rue St. Victor 3, B-4500 Huy, Belgium. paul.warnant@infonie.be

Poplar bud resinoids are a potential source of natural antioxidants. As poplar culture today involves many hybrids, a simple screening test to assess antioxidant properties was proposed. This method used the second derivative of the UV spectra at 233 nm of the iron induced peroxidienes resulting from linoleic acid peroxidation. Kinetic data showed a lag period followed by a quadratic increase in peroxidienes. These two phases were more clearly separated using the square root of the data. An acceptable linear fitting of the length of the lag phase with antioxidant concentration was observed. Calibrating the experimental test with BHA therefore allowed an antioxidant assessment as "BHA equivalent". First results clustered well with taxonomic data, with typically 0.5, 0.15 and 0.08 "BHA equivalent" for P. nigra, P. X euramericana and P. X interamericana, respectively.

PMID: 14987719 [PubMed - indexed for MEDLINE]


55: J Med Food. 2003 Winter;6(4):387-90.

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Effects of chrysin on urinary testosterone levels in human males.

Gambelunghe C, Rossi R, Sommavilla M, Ferranti C, Rossi R, Ciculi C, Gizzi S, Micheletti A, Rufini S.

Department of Clinical and Experimental Medicine, Division of Sports Medicine-Laboratorio delle Attivita Motorie e Sportive, University of Perugia, Perugia, Italy. labsport@unipg.it

The equilibrium of sexual hormones in both sexes is controlled in vertebrates by the enzyme aromatase, a member of the cytochrome P450 superfamily, which catalyzes the conversion of androstenedione and testosterone into estrone and estradiol, respectively. Flavonoids are diphenolic compounds present in whole grains, legumes, fruits, and vegetables that are strongly implicated as protective in coronary heart disease, stroke, and cancer. One flavonoid, chrysin, found in high concentrations in honey and propolis, has been shown to be an inhibitor of aromatase enzyme activity. These foods are often used as supplements, particulary by sportsmen for their energetic and antioxidant properties. The aim of this study was to verify if daily treatment for 21 days with propolis and honey, containing chrysin, would modify urinary concentrations of testosterone in volunteer male subjects. In fact, aromatase inhibition by chrysin could block the conversion of androgens into estrogens with a consequent increase of testosterone, eventually measurable in urine samples. The obtained data did not show alterations of the levels of testosterone in the volunteers after 7, 14, and 21 days of treatment in comparison with baseline values and compared with measurements on the control subjects at the same time. In conclusion, the use of these foods for 21 days at the doses usually taken as oral supplementation does not have effects on the equilibrium of testosterone in human males.

PMID: 14977449 [PubMed - indexed for MEDLINE]


56: Mol Divers. 2004;8(1):21-33.

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Creating molecular diversity from antioxidants in Brazilian propolis. Combination of TOPS-MODE QSAR and virtual structure generation.

Estrada E, Quincoces JA, Patlewicz G.

Safety, and Environmental Assurance Centre (SEAC), Unilever Colworth, Sharnbrook, Bedford, UK. estrada66@yahoo.com

A QSAR model for antioxidative activity based on the Sub-Structural Molecular Design (TOPS-MODE) approach is developed for a series of compounds present in Brazilian propolis. This approach permitted the structural interpretation of the antioxidative activity of these compounds in terms of bond contributions. By these means we have identified the structural groups and regions that contribute to the antioxidative activity of the cinnamic acid and flavonoid derivatives present in the propolis. These results were then used to identify the positions and substituents to be used in a virtual compound generation experiment. Using this approach a total of 327 compounds were generated from which more than 70 are predicted to be more active than the most powerful antioxidants in the Brazilian propolis. From these 70 compounds less than 20 have been reported in the literature. Consequently, a high proportion of novel compounds with potential antioxidative activity has been identified by the current approach. This contributes to enhance the molecular diversity of the analogues of Brazilian propolis compounds with antioxidative properties.

PMID: 14964785 [PubMed - indexed for MEDLINE]


57: Acta Pharm. 2003 Dec;53(4):275-85.

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Analysis of propolis from the continental and Adriatic regions of Croatia.

Kosalec I, Bakmaz M, Pepeljnjak S.

Institute of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia. ivan.kosalec@zg.htnet.hr

Thin-layer chromatography of ethanolic extract of propolis (EEP) from the continental and Adriatic regions of Croatia showed that 72.2% of propolis samples contain galangin, 88.8% of samples contain kaempferol, naringenin and apigenin and 66.6% of samples contain caffeic acid. Caffeic acid, pinocembrin, galangin, chrysin and naringenin were analyzed by HPLC. In all samples, pinocembrin was the dominant flavonoid. In samples from the Adriatic region, concentration of pinocembrin ranged from 0.03 to 6.14% (x = 2.87%) and in the continental region samples from 0 to 4.74% (x = 2.84%). Chrysin was found in all propolis samples in a concentration ranging from 0.22 to 5.32% (x = 1.86%) in the continental region samples and from 0.03 to 3.64% (x = 1.96%) in samples from the Adriatic region. Chrysin was followed by naringenin, ranging from 0 to 1.14% (x = 0.42%) in samples from the Adriatic region and from 0.22 to 2.41% (x = 0.60%) in the continental region samples. Concentration of caffeic acid ranged from 0 to 10.11% (x = 2.69%) in the Adriatic region samples and from 0.27 to 2.67% (x = 1.37%) in samples from the continental region of Croatia. Results of HPLC analyses suggest that propolis samples collected from various parts of Croatia do not differ markedly in contents of chrysin, pinocembrin, naringenin and galangin but differ in the concentration of caffeic acid. All EEPs significantly inhibited the growth of Bacillus subtilis in comparison with the control (80% ethanol) (p < 0.05), showing inhibition zones of 16 +/- 2 mm for samples from the continental region, and of 18 +/- 3 mm for samples from the Adriatic region. There was no significant difference in antimicrobial activity of EEPs from the continental and Adriatic regions of Croatia, suggesting that bactericidal activity depends on synergism of all phenolic compounds.

PMID: 14769234 [PubMed - indexed for MEDLINE]


58: J Appl Toxicol. 2004 Jan-Feb;24(1):27-35.

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Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats.

Ozen S, Akyol O, Iraz M, Sogut S, Ozugurlu F, Ozyurt H, Odaci E, Yildirim Z.

Department of Pathology, Yuzuncu Yil University Medical School, Van, Turkey.

We have investigated the effect of caffeic acid phenethyl ester (CAPE) on cisplatin-induced nephrotoxicity in rats. Administration of a single dose of cisplatin resulted in the elevation of blood urea nitrogen and creatinine in serum, as well as nitric oxide in kidney tissue of rats. Cisplatin also caused reduction of catalase (P < 0.0001), superoxide dismutase (P = 0.149) and glutathrone peroxidase (P < 0.0001) activities in kidney tissue. Although cisplatin caused elevation in malondialdehyde levels and myeloperoxidase activities in kidney tissue, they were not statistically significant. Caffeic acid phenethyl ester was found to be protective against cisplatin-induced antioxidant enzyme reductions. Treatment with free-radical scavenger CAPE attenuated the increase in plasma blood urea nitrogen and kidney nitric oxide levels, and showed histopathological protection against cisplatin-induced acute renal failure. Extensive epithelial cell vacuolization, swelling, desquamation and necrosis were observed in the kidney of the cisplatin-treated rat. There were also larger tubular lumens in cisplatin-treated rats than those of the control and the CAPE groups. Caffeic acid phenethyl ester caused a marked reduction in the extent of tubular damage. It is concluded that administration of cisplatin imposes an oxidative stress to renal tissue and CAPE confers protection against the oxidative damage associated with cisplatin. This mechanism may be attributed to its free-oxygen-radical scavenging activity.
Copyright 2004 John Wiley & Sons, Ltd.

PMID: 14745844 [PubMed - indexed for MEDLINE]


59: Biosci Biotechnol Biochem. 2004 Jan;68(1):260-2.

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A new prenylated flavonoid from propolis collected in Okinawa, Japan.

Kumazawa S, Goto H, Hamasaka T, Fukumoto S, Fujimoto T, Nakayama T.

Laboratory of Functional Food Science and COE Program in the 21st Century, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan. kumazawa@smail.u-shizuoka-ken.ac.jp

The new prenylflavonoid, isonymphaeol-B (1), together with three known compounds, nymphaeol-A (2), nymphaeol-B (3), and nymphaeol-C (4), were isolated from propolis collected in Okinawa, the southern-most prefecture of Japan. The structure of each compound was determined by spectral methods, including mass spectrometry and 2D NMR. Each compound had 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging activity.

PMID: 14745198 [PubMed - indexed for MEDLINE]


60: Neurosci Lett. 2004 Jan 30;355(3):231-5.

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Antioxidant propolis attenuates kainate-induced neurotoxicity via adenosine A1 receptor modulation in the rat.

Kwon YS, Park DH, Shin EJ, Kwon MS, Ko KH, Kim WK, Jhoo JH, Jhoo WK, Wie MB, Jung BD, Kim HC.

Neurotoxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.

We examined the effects of the antioxidant propolis on seizures induced by kainic acid (KA). Sprague-Dawley rats received propolis (75 and 150 mg/kg, p.o.) five times at 12 h intervals. KA (10 mg/kg, i.p.) was injected 1 h after the last propolis treatment. Pretreatment with propolis significantly attenuated KA-induced seizures and KA-induced increases in hippocampal AP-1 DNA binding activity in a dose-dependent manner. KA induced increases in the levels of malondialdehyde and protein carbonyl, and a decrease in the ratio of GSH/GSSG. These oxidative stresses and neuronal degenerations were significantly attenuated by pretreatment with propolis. The neuroprotective effects of propolis appeared to be counteracted by adenosine receptor antagonists [A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (25 or 50 microg/kg); A2A antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1 mg/kg); and A2B antagonist, alloxazine (1.5 or 3.0 mg/kg)]. However, this counteraction was most pronounced in the presence of the A1 antagonist. Our results suggest that the protective effect of propolis against KA-induced neurotoxic oxidative damage is, at least in part, via adenosine A1 receptor modulation.

PMID: 14732473 [PubMed - indexed for MEDLINE]


61: Biochem Pharmacol. 2004 Jan 1;67(1):53-66.

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Propolin C from propolis induces apoptosis through activating caspases, Bid and cytochrome c release in human melanoma cells.

Chen CN, Wu CL, Lin JK.

Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Section 1, Jen-Ai Road, 100, ROC, Taipei, Taiwan.

We had demonstrated that two prenylflavanones, propolin A and propolin B, isolated and characterized from Taiwanese propolis, induced apoptosis in human melanoma cells and significantly inhibited xanthine oxidase activity. Here, we have isolated a third compound called propolin C. The chemical structure of propolin C has been characterized by NMR and HRMS spectra, and was identical to nymphaeol-A. However, no biological activities of this compound have ever been reported. In the present study, propolin C effectively induced a cytotoxic effect on human melanoma cells, with an IC(50) of about 8.5 microM. DNA flow cytometric analysis indicated that propolin C actively induced apoptosis in human melanoma cells and there is a marked loss of cells from the G2/M phase of the cell cycle. To address the mechanism of the apoptosis effect of propolin C, we evaluated the effect of propolin C on induction of apoptosis-related proteins in human melanoma cells. The levels of procaspase-8, Bid, procaspase-3, and poly(ADP-ribose) polymerase were decreased in dose- or time course-dependent manners. Moreover, propolin C was capable of releasing cytochrome c from mitochondria to cytosol. The findings suggest that propolin C may activate a mitochondria-mediated apoptosis pathway. On other hand, propolin C is a potential antioxidant agent and shows a strong capability to scavenge free radicals and inhibit on xanthine oxidase activity with IC(50) of about 17.0microM. In conclusion, the isolation and characterization of propolin C from bee propolis are described for the first time, and this compound is a powerful inducer of apoptosis in human melanoma cells.

PMID: 14667928 [PubMed - indexed for MEDLINE]


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

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

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

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

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

PMID: 14637186 [PubMed - indexed for MEDLINE]


63: Org Biomol Chem. 2003 May 7;1(9):1452-4.

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Efficient radical scavenging ability of artepillin C, a major component of Brazilian propolis, and the mechanism.

Nakanishi I, Uto Y, Ohkubo K, Miyazaki K, Yakumaru H, Urano S, Okuda H, Ueda J, Ozawa T, Fukuhara K, Fukuzumi S, Nagasawa H, Hori H, Ikota N.

Redox Regulation Research Group, Research Center for Radiation Safety, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan. nakanis@nirs.go.jp

Hydrogen transfer from artepillin C to cumylperoxyl radical proceeds via one-step hydrogen atom transfer rather than via electron transfer, the rate constant of which is comparable to that of (+)-catechin, indicating that artepillin C can act as an efficient antioxidant.

PMID: 12926271 [PubMed - indexed for MEDLINE]


64: Cell Biochem Funct. 2003 Sep;21(3):283-9.

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Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain.

Irmak MK, Fadillioglu E, Sogut S, Erdogan H, Gulec M, Ozer M, Yagmurca M, Gozukara ME.

Department of Histology and Embryology, Gulhane Military Medical Academy, Ankara, Turkey. mkirmak@gata.edu.tr

Oxygen-derived free radicals have been implicated in the pathogenesis of cerebral injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. The purpose of the present study was to investigate the effects of ischaemia and subsequent reperfusion on rat brain and to investigate the effects of two free radical scavengers, CAPE and alpha-tocopherol, on this in vivo model of cerebral injury. Ischaemia was induced by bilateral occlusion of the carotid arteries for 20 min and reperfusion was achieved by releasing the occlusion to restore the circulation for 20 min. Control rats underwent a sham operation. CAPE at 10 micromol kg(-1) or alpha-tocopherol at 25 micromol kg(-1) was administered intraperitoneally before reperfusion. Reperfusion led to significant increase in the activity of xanthine oxidase and higher malondialdehyde levels in the brain. Acute administration of both CAPE and alpha-tocopherol suppressed ischaemia-reperfusion-induced cerebral lipid peroxidation and injury, but CAPE seems to offer a better therapeutic advantage over alpha-tocopherol. Copyright 2003 John Wiley & Sons, Ltd.

PMID: 12910483 [PubMed - indexed for MEDLINE]


65: Brain Res Mol Brain Res. 2003 Jul 23;115(2):111-20.

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Caffeic acid phenethyl ester (CAPE) prevents inflammatory stress in organotypic hippocampal slice cultures.

Montpied P, de Bock F, Rondouin G, Niel G, Briant L, Courseau AS, Lerner-Natoli M, Bockaert J.

Faculte de Pharmacie, CNRS-UMR 5094, 15 Avenue Charles Flahault, 34060 Montpellier Cedex 2, France. pascale.montpied@ibph.pharma.univ-montp1.fr

Caffeic acid phenethyl ester (CAPE) is an antioxidant component of propolis, a natural product secreted by honeybee. Recent literature shows that CAPE inhibits nuclear factor kappa B (NFkappaB) activation in cell lines. Since NFkappaB was shown to be a crucial factor in neuroinflammation and to be associated with some neuropathologies, CAPE might reduce these disorders in brain too and have therapeutic applications. To test this hypothesis we used a model of endotoxic insult (interferon-gamma, followed by lipopolysaccharide) on rat organotypic hippocampal cultures. Cerebral inflammatory responses were strongly inhibited by CAPE (100 microM): reductions of NFkappaB nuclear activity, tumor necrosis factor alpha and nitric oxide productions were observed. At the dose of maximal effects (100 microM), an increase of cAMP-responsive element binding protein (CREB) activity, which anti-inflammatory role is well known, was seen. We compared CAPE effects with those of other drugs: anti-inflammatory as acetyl-salicylate and dexamethasone (glucocorticoid), antioxidant as pyrrolidine dithiocarbamate, or selective permeant inhibitor of NFkappaB as SN 50 peptide. These studies lead us to conclude that CAPE presents an interesting and original neuropharmacological profile compared to these drugs and might be helpful in the prevention of neurotoxic events due to excessive inflammatory reaction in brain. CAPE interferes with several effectors of neuroinflammation that might have complementary and synergic effects and allows a rather durable control since an acute treatment at the time of endotoxin exposure allows to control inflammatory factors for over 48 h.

PMID: 12877982 [PubMed - indexed for MEDLINE]


66: J Nat Prod. 2003 Apr;66(4):503-6.

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Cytotoxic prenylflavanones from Taiwanese propolis.

Chen CN, Wu CL, Shy HS, Lin JK.

Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-ai Road, Taipei, Taiwan 100, Republic of China.

Two new prenylflavanones, propolin A (2) and propolin B (3), were isolated and characterized from Taiwanese propolis. Both compounds were found to have cytotoxic properties against three cancer cell lines. DNA content analyses and DNA fragmentation indicated that propolin A (2) efficiently induced apoptosis in cancer cell lines, but had no effect on the cell cycle program. Furthermore, both propolin A (2) and B (3) are potential antioxidant agents and show strong scavenging effects against most types of free radicals.

PMID: 12713401 [PubMed - indexed for MEDLINE]


67: Redox Rep. 2002;7(5):347-50.

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Free radical scavenging activity of propolis.

Ichikawa H, Satoh K, Tobe T, Yasuda I, Ushio F, Matsumoto K, Endo K, Ookubo C.

Tokyo Metropolitan Research Laboratory of Public Health, Tokyo, Japan. ichikawa@tokyo-eiken.go.jp

We investigated the radical scavenging activity of propolis by ESR spectroscopy using spin trapping method. In addition, we examined the influence of a diet of 2% propolis on mice under oxidative stress. At low concentrations, the methanolic extract of propolis exhibited strong scavenging activity in vitro towards both the superoxide anion radical, generated by the hypoxanthine-xanthine oxidase reaction, and the NO radical, generated from the mixture of NOC-7 (NO generator) and carboxy-PTIO (spin trapping agent). An inhibitory effect of propolis on lipid peroxidation in vivo was observed, as determined by measurement of thiobarbituric acid-reactive substances in mouse liver homogenate. The level of vitamin C in the brain of mice under oxidative stress significantly increased compared with control mice under atmosphere, which was not observed in the mice given 2% propolis. The level of alpha-tocopherol in the brain of mice given 2% propolis significantly increased compared with control mice under atmosphere, which was not observed in mice under oxidative stress. SOD activity in the brain and plasma of mice given 2% propolis significantly decreased under atmosphere and oxidative stress compared with control mice. These results suggest that propolis possesses potent antioxidant activity in vitro and in vivo.

PMID: 12688527 [PubMed - indexed for MEDLINE]


68: Arch Pharm Res. 2003 Jan;26(1):43-6.

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In vivo anti-oxidant activities of tectochrysin.

Lee S, Kim KS, Park Y, Shin KH, Kim BK.

College of Pharmacy, Seoul National University, Seoul 151-742, Korea.

The anti-oxidant activities of tectochrysin, a major compound of propolis, were investigated. Tectochrysin exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats. Tectochrysin tested exhibited a lipid peroxidation causing a significant decrease in MDA production in TBA-reactant assay. Tectochrysin was strong in the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase, catalase and glutathione peroxidase activities in CCl4-intoxicated rats. These results suggest that tectochrysin possess not only the anti-oxidant, but also the activities in CCl4-intoxicated rats. Especially, tectochrysin was found to cause significant increases in the rat liver cytosolic SOD, catalase, GSH-px activities as well as a significant decrease in the MDA production.

PMID: 12568357 [PubMed - indexed for MEDLINE]


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

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

Russo A, Longo R, Vanella A.

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


70: Pharmacol Ther. 2002 Nov-Dec;96(2-3):67-202.

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The biochemistry and medical significance of the flavonoids.

Havsteen BH.

Department of Biochemistry, University of Kiel, Olshausenstrasse 40, D-24098, Kiel, Germany. benthavs@worldonline.dk

Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells. The flavonoids are used by botanists for taxonomical classification. They regulate plant growth by inhibition of the exocytosis of the auxin indolyl acetic acid, as well as by induction of gene expression, and they influence other biological cells in numerous ways. Flavonoids inhibit or kill many bacterial strains, inhibit important viral enzymes, such as reverse transcriptase and protease, and destroy some pathogenic protozoans. Yet, their toxicity to animal cells is low. Flavonoids are major functional components of many herbal and insect preparations for medical use, e.g., propolis (bee's glue) and honey, which have been used since ancient times. The daily intake of flavonoids with normal food, especially fruit and vegetables, is 1-2 g. Modern authorised physicians are increasing their use of pure flavonoids to treat many important common diseases, due to their proven ability to inhibit specific enzymes, to simulate some hormones and neurotransmitters, and to scavenge free radicals.

Publication Types:

       Review


PMID: 12453566 [PubMed - indexed for MEDLINE]


71: Am J Chin Med. 2002;30(2-3):245-54.

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Cytoprotection by propolis ethanol extract of acute absolute ethanol-induced gastric mucosal lesions.

Liu CF, Lin CC, Lin MH, Lin YS, Lin SC.

National Taipei College of Nursing, Taiwan, ROC.

Acute p.o. administration of absolute ethanol (1.0 ml/kg) to fasted rats produced extensive necrosis of gastric mucosa. Pretreatment with p.o. administration of propolis ethanol extract (PEE) could effectively and dose-dependently prevent such necrosis. This protective effect is called "cytoprotection. "The maximal cytoprotective effect against absolute ethanol (AE)-induced gastric mucosal lesion was observed 1 hour after PEE administration. A gross examination of the gastric mucosa showed a marked improvement in groups receiving PEE. In order to further investigate the gastric protective mechanism of PEE, lipid peroxidation (LPO) levels in vivo and in vitro were estimated. PEE exhibited dose-dependent superoxide scavenging activity and antioxidant effects on AE-induced LPO in rat gastric mucosal homogenates. It was concluded that the gastric protective mechanism of PEE was due, at least in part, to its ability to inhibit LPO, and hence indirectly protect the gastric mucosa from oxidative stress.

PMID: 12230013 [PubMed - indexed for MEDLINE]


72: Free Radic Res. 2002 Jun;36(6):711-6.

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In vitro antioxidant profile of phenolic acid derivatives.

Cos P, Rajan P, Vedernikova I, Calomme M, Pieters L, Vlietinck AJ, Augustyns K, Haemers A, Vanden Berghe D.

Laboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

Several caffeic acid esters isolated from propolis exhibit interesting antioxidant properties, but their in vivo use is compromised by hydrolysis of the ester bond in the gastrointestinal tract. Therefore, a series of caffeic acid amides were synthesized and their in vitro antioxidant profile was determined. A series of hydroxybenzoic acids, hydroxycinnamic acids, and the synthesized caffeic acid amides were tested for both their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and microsomal lipid peroxidation-inhibiting activity. Some of the highly active antioxidants were further tested by means of electron paramagnetic resonance for their hydroxyl radical scavenging activity. Since a promising antioxidant compound should show a lipid peroxidation-inhibiting activity at micromolar level and a low cytotoxicity, the cytotoxicity of the phenolic compounds was also studied. In all the assays used, the caffeic acid anilides and the caffeic acid dopamine amide showed an interesting antioxidant activity.

PMID: 12180197 [PubMed - indexed for MEDLINE]


73: Phytother Res. 2002 Jun;16(4):340-7.

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Evaluation of antilipid peroxidative action of propolis ethanol extract.

Shinohara R, Ohta Y, Hayashi T, Ikeno T.

Department of Biochemistry, School of Health Sciences, Fujita Health University, Toyoake, Aichi 470-1192, Japan.

The antilipid peroxidative action of the ethanol extract of Brazilian propolis at a concentration of 47% (w/v) was evaluated by examining the inhibitory effect of the extract on the formation of hydroperoxide- and endoperoxide-type lipid peroxides during heating of authentic polyunsaturated fatty acids and on Fe(3+)-ADP/ascorbic acid- and Fe(3+)-ADP/NADPH-dependent lipid peroxidation reactions in rat liver microsomes. Hydroperoxide-type lipid peroxides were measured by the haemoglobin-methylene blue method and endoperoxide-type lipid peroxides by the thiobarbituric acid (TBA), Fe(3+)-TBA and LPO-586 methods. Propolis ethanol extract inhibited dose-dependently the formation of hydroperoxide- and endoperoxide-type lipid peroxides during heating of linoleic acid, linolenic acid or arachidonic acid and the amount of the extract causing a half inhibition of these lipid peroxide formations ranged between 20 and 75 microg. Propolis ethanol extract inhibited dose-dependently both Fe(3+)-ADP/ascorbic acid- and Fe(3+)-ADP/NADPH-dependent lipid peroxidation reactions in rat liver microsomes when lipid peroxides produced in both reactions were measured by the TBA method. The amount of propolis extract causing a half inhibition of the Fe(3+)-ADP/ascorbic acid-dependent lipid peroxidation was about 5 microg, while that of the extract causing a half inhibition of the Fe(3+)-ADP/NADPH-dependent lipid peroxidation was about 0.15 microg. These results indicate that the propolis ethanol extract exerts an antilipid peroxidative action at very low doses. Copyright 2002 John Wiley & Sons, Ltd.

PMID: 12112290 [PubMed - indexed for MEDLINE]


74: Z Naturforsch [C]. 2002 Mar-Apr;57(3-4):395-402.

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Egyptian propolis: 3. Antioxidant, antimicrobial activities and chemical composition of propolis from reclaimed lands.

Hegazi AG, Abd El Hady FK.

Department of Parasitology, National Research Center, Dokki, Giza, Egypt. ahmedgaffer@mailer.suc.eun.eg

The free radical scavenging effect of two propolis samples collected from reclaimed land, Egypt as well as of vitamin C and caffeic acid in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical system was determined. The antimicrobial (Staphylococcus aureus; Escherichia coli and Candida albicans) activity was also investigated. The results of the free radical scavenging effect of El-Saff and Ismailia propolis showed a concentration-dependent activity. The antioxidant activity was varied according to the examined material. It was obvious that caffeic acid and vitamin C showed the highest activity if compared with the propolis samples. El- Saff propolis had a higher antioxidant activity than Ismailia propolis, it showed a higher antibacterial activity against Staphylococcus aureus and a higher anti-fungal activity against Candida albicans. While the Ismailia propolis had a higher antibacterial activity against Escherichia coli, than El-Saff propolis. The chemical composition of propolis samples was investigated by GC/MS, where 75 compounds were identified, 22 being new for propolis. The Ismailia propolis was characterized by the presence of a highly significant amount of aromatic acid esters (47.3%) and triterpenoids (17.3%), while El-Saff propolis contained 3% and 1.9% respectively. The new esters belonged to 4-methoxyhydrocinnamic acid, hydroferulic acid and ferulic acid. El-Saff propolis had a very high significant amount (27%) of 2,6-bis-(pentanyloxy)-4-pentanylphenethanol, which is also a new compound for propolis.

PMID: 12064746 [PubMed - indexed for MEDLINE]


75: Z Naturforsch [C]. 2002 Mar-Apr;57(3-4):372-8.

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Polyisoprenylated benzophenones in cuban propolis; biological activity of nemorosone.

Cuesta-Rubio O, Frontana-Uribe BA, Ramirez-Apan T, Cardenas J.

Instituto de Farmacia y Alimentos, Universidad de la Habana, Cuba.

The Copey tree (Clusia rosea) has a large distribution in Cuba and its floral resin is a rich source of polyisoprenylated benzophenones. To determine the presence of these natural products, we carried out a study by HPLC of 21 propolis samples produced by honey bees (Apis mellifera) from different provinces of Cuba. Nemorosone resulted to be the most abundant polyisoprenylated benzophenone and the mixture of xanthochymol and guttiferone E was also observed, but in minor proportion. We studied the biological activity of the pure natural product nemorosone and its methyl derivatives. We found that nemorosone has cytotoxic activity against epitheloid carcinoma (HeLa), epidermoid carcinoma (Hep-2), prostate cancer (PC-3) and central nervous system cancer (U251). It also exhibited antioxidant capacity. Methylated nemorosone exhibited less biological activity than the natural product.

PMID: 12064743 [PubMed - indexed for MEDLINE]


76: J Nat Prod. 2002 May;65(5):673-6.

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Constituents of Chinese propolis and their antiproliferative activities.

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

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

Two new flavonoids, 3-O-[(S)-2-methylbutyroyl]pinobanksin (1) and 6-cinnamylchrysin (2), were isolated from the EtOAc-soluble fraction of the MeOH extract of Chinese propolis, along with 12 known compounds (3-14). The structures of the isolated compounds were elucidated on the basis of spectroscopic and chemical analyses. The isolated compounds were tested for their antiproliferative activity toward five different cancer cell lines. Benzyl caffeate (13) and phenethyl caffeate (14) showed potent antiproliferative activity toward tested cell lines with a selective activity toward colon 26-L5 carcinoma cell line (EC(50) values: 13, 1.01; 14, 0.30 microM).

PMID: 12027739 [PubMed - indexed for MEDLINE]


77: J Ethnopharmacol. 2002 Apr;80(1):67-73.

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Antiproliferative activity of the Netherlands propolis and its active principles in cancer cell lines.

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

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

The MeOH extract of the Netherlands propolis showed promising antiproliferative activity toward highly liver-metastatic murine colon 26-L5 carcinoma with an EC(50) value of 3.5 microg/ml. Further, antiproliferative activity-guided purification of the MeOH extract led us to isolate four flavonoids (1-4), seven cinnamic acid derivatives (5-11) and two new glycerol derivatives (12, 13), whose structures were elucidated on the basis of spectral analysis. The isolated compounds were tested for their antiproliferative activity against murine colon 26-L5, murine B16-BL6 melanoma, human HT-1080 fibrosarcoma and human lung A549 adenocarcinoma cell lines. The benzyl (9), phenethyl (10) and cinnamyl caffeates (11) possessed potent antiproliferative activities with EC(50) values of 0.288, 1.76 and 0.114 microM, respectively, toward colon 26-L5 carcinoma. These caffeates were considered to be active constituents of the Netherlands propolis in their antiproliferative activity. The antioxidative activity of these caffeates may play an important role in their antiproliferative activities.

PMID: 11891088 [PubMed - indexed for MEDLINE]


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

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

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

Department of Ophthalmology, Inonu University School of Medicine, Malatya, Turkey. ytotan@usa.net

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

PMID: 11852431 [PubMed - indexed for MEDLINE]


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

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Recent progress in pharmacological research of propolis.

Banskota AH, Tezuka Y, Kadota S.

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

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

Publication Types:

       Review


PMID: 11746834 [PubMed - indexed for MEDLINE]


80: Cell Biochem Funct. 2001 Dec;19(4):259-63.

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Caffeic acid phenethyl ester changes the indices of oxidative stress in serum of rats with renal ischaemia-reperfusion injury.

Ozyurt H, Irmak MK, Akyol O, Sogut S.

Department of Biochemistry, Faculty of Medicine, Inonu University, Malatya, Turkey.

Oxygen-derived free radicals have been implicated in the pathogenesis of renal injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. To investigate whether treatment with either CAPE or alpha-tocopherol modifies the levels of the endogenous indices of oxidant stress, we examined their effects on an in vivo model of renal ischaemia-reperfusion injury in rats. CAPE at 10 micromol kg(-1) or alpha-tocopherol at 10 mg kg(-1) was administered intraperitoneally before reperfusion. Acute administration of both CAPE and alpha-tocopherol altered the indices of oxidative stress differently in renal ischaemia-reperfusion injury. Copyright 2001 John Wiley & Sons, Ltd.

PMID: 11746206 [PubMed - indexed for MEDLINE]


81: Cancer Lett. 2002 Jan 10;175(1):53-61.

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Caffeic acid phenethyl ester inhibits nitric oxide synthase gene expression and enzyme activity.

Song YS, Park EH, Hur GM, Ryu YS, Lee YS, Lee JY, Kim YM, Jin C.

Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, 130-650, Seoul, South Korea.

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. Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, has been identified to show anti-inflammatory, anti-viral and anti-cancer activities. The present study, therefore, examined effects of CAPE on iNOS expression and activity of iNOS enzyme itself. Treatment of RAW 264.7 cells with CAPE significantly inhibited NO production and iNOS protein expression induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). CAPE 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 reporter gene, revealed that CAPE inhibited the iNOS promoter activity induced by LPS plus IFN-gamma through the NF-kappaB sites of the iNOS promoter. In addition, CAPE directly interfered with the catalytic activity of murine recombinant iNOS enzyme. These results suggest that CAPE may exert its anti-inflammatory effect by inhibiting the iNOS gene expression at the transcriptional level through the suppression of NF-kappaB activation, and by directly inhibiting the catalytic activity of iNOS.

PMID: 11734336 [PubMed - indexed for MEDLINE]


82: J Agric Food Chem. 2001 Nov;49(11):5615-9.

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Effect of caffeic acid phenethyl ester, an antioxidant from propolis, on inducing apoptosis in human leukemic HL-60 cells.

Chen YJ, Shiao MS, Hsu ML, Tsai TH, Wang SY.

Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan 11221.

Caffeic acid phenethyl ester (CAPE) is an active component isolated from propolis. The aim of this study was to investigate the mechanism of CAPE-induced apoptosis in human leukemic HL-60 cells. It was found that CAPE entered HL-60 cells very quickly and then inhibited their survival in a concentration- and time-dependent manner. CAPE induced characteristic DNA fragmentation and morphological changes typical of apoptosis in these cells. Estimation of the apoptotic percentage showed a time-dependent increase after CAPE (6 microg/mL) treatment (up to 66.7 +/- 2.0% at 72 h). Treatment with CAPE caused rapid activation of caspase-3 after 4 h, down-regulation of Bcl-2 expression after 6 h, and up-regulation of Bax expression after 16 h. These results suggest that CAPE is a potent apoptosis-inducing agent; its action is accompanied by activation of caspase-3, down-regulation of Bcl-2, and up-regulation of Bax in human leukemic HL-60 cells.

PMID: 11714368 [PubMed - indexed for MEDLINE]


83: Z Naturforsch [C]. 2001 Jul-Aug;56(7-8):593-6.

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New bioactive chalcones in propolis from El Salvador.

Popova M, Bankova V, Spassov S, Tsvetkova I, Naydenski C, Silva MV, Tsartsarova M.

Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia.

2',3'-Dihydroxy-4,4'-dimethoxychalcone (1) and 2',3',4-trihydroxy-4'-methoxy-chalcone, two new chalcones, were isolated from propolis from El Salvador. The compounds showed significant antibacterial and antifungal activity and moderate toxicity to Artemia salina nauplii.

PMID: 11531095 [PubMed - indexed for MEDLINE]


84: Urol Res. 2001 Jun;29(3):190-3.

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The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with alpha-tocopherol in rat kidneys.

Irmak MK, Koltuksuz U, Kutlu NO, Yagmurca M, Ozyurt H, Karaman A, Akyol O.

Department of Biochemistry, Faculty of Medicine, Inonu University, Malatya, Turkey.

Oxygen-derived free radicals have been implicated in the pathogenesis of renal injury after ischemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant and anti-inflammatory properties. To determine whether CAPE offers any advantage over alpha-tocopherol, we compared their effects on an in vivo model of renal ischemia-reperfusion injury in rats. CAPE at 10 micromol/kg or alpha-tocopherol at 10 mg/kg was administered intraperitoneally before reperfusion. Acute administration of CAPE suppressed ischemia-reperfusion induced renal lipid peroxidation and tissue injury more than alpha-tocopherol. CAPE may therefore offer a therapeutic advantage in acute injury settings.

PMID: 11482445 [PubMed - indexed for MEDLINE]


85: J Ethnopharmacol. 2001 Jul;76(2):165-70.

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Antioxidant activity of Argentine propolis extracts.

Isla MI, Nieva Moreno MI, Sampietro AR, Vattuone MA.

Catedra de Fitoquimica, Instituto de Estudios Vegetales 'Dr Antonio Rodolfo Sampietro', Facultad de Bioquimica, Quimica y Farmacia, Universidad Nacional de Tucuman, Ayacucho 471, 4000, San Miguel de Tucuman, Argentina.

Propolis is used in Argentine folk medicine. We have examined its possible protective action against oxidative modification of lipid in unfractionated serum. The kinetics of copper-induced oxidation was continuously monitored by measuring the formation of conjugated dienes, as the increase in the absorbance at 234 nm. According to the kinetics of oxidation, the propolis were classified in three different groups. Group I (CE, CO, BO, MO, BE) inhibited lipid oxidation during the initiation and propagation phases even at low concentrations. Group II (SP, CA, AM) increased the lag-phase for conjugated diene formation. All propolis in groups I and II diminished the maximal rate of diene production and the maximal amount of dienes produced. Group III (PA, RA, FE, VR, TV) had no effect on the lipid oxidation. The extent of lipoprotein oxidation was measured by the thiobarbituric acid reactive substance assay. Generation of malondialdehyde-like substances was inhibited and delayed by the presence of propolis extracts from group I and II. Our results justify the use of propolis (groups I and II) as a source of natural antioxidants.

PMID: 11390131 [PubMed - indexed for MEDLINE]


86: Am J Contact Dermat. 2001 Jun;12(2):93-102.

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Contact allergy to balsam of Peru. II. Patch test results in 102 patients with selected balsam of Peru constituents.

Hausen BM.

Dermatologisches Zentrum Buxtehude, Germany.

BACKGROUND: In Switzerland, Germany, and Austria, allergic reactions to balsam of Peru (BP) have now made it the third most common contact allergen. OBJECTIVE: A series of 20 single BP constituents (including resorcinol monobenzoate), established in 1995, was used for patch tests in patients with a positive reaction to BP in the standard series. MATERIALS AND METHODS: Between 1995 and 1998, 2,273 patients were tested with the standard series, including BP, fragrance mix (FM), and propolis. Patients positive for BP were requested to participate in a further test using the 19 compounds of the BP constituents and resorcin monobenzoate (BP series); 102 patients agreed and were patch tested. The results of the 72-hour reading were used for the evaluation. RESULTS: A total of 93 patients reacted to 1 or more of the BP series compounds. Positive reactions were seen, in decreasing order, to cinnamic alcohol, cinnamic acid, coniferyl benzoate, benzoic acid, cinnamyl cinnamate, eugenol, resorcinol monobenzoate, coniferyl alcohol, and benzyl alcohol. There were no positive reactions to vanillin or ferulic acid. A correlation between skin lesions and frequent consumption of sweets was found in 7 patients with major positive test reactions to coniferyl benzoate and benzyl alcohol. Most of the reactions to eugenol and isoeugenol had less to do with BP itself than with a primary sensitization to fragrances. Although resorcin monobenzoate (RMB) has up to now not been detected in BP, 16 patients reacted distinctly to this compound. Eleven were strong smokers; the remaining ones had contact with plastic materials that have been reported to contain RMB. RMB is used frequently as an antioxidant in synthetic material. When these patients stopped smoking, the skin lesions cleared. However, consumption of sweets caused recurrences. CONCLUSION: The evaluation of reactions to single constituents of BP by testing with the special BP series facilitates understanding how sensitization may be acquired. The allergen may prove to be BP itself or 1 or more of its constituents. Testing for the constituents of this series may provide patients with a more specific allergen diagnosis and may facilitate improved therapy. BP may function as an important indicator for contact allergy to RMB. Copyright 2001 by W.B. Saunders Company.

PMID: 11381345 [PubMed - indexed for MEDLINE]


87: Z Naturforsch [C]. 2001 Mar-Apr;56(3-4):269-72.

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Propolis from Chilean matorral hives.

Munoz O, Pena RC, Ureta E, Montenegro G, Timmermann BN.

Faculty of Sciences, Universidad de Chile, Palmeras, Santiago de Chile. omunoz@abello.dic.uchile.cl

Viscidone (0.5%), vanillin, 3',4'-(methylendioxy)acetophenone, 3-ethoxy-4-methoxybenzaldehyde, cinnamic acid, 3-methoxy-4-hydroxymethyl ester were isolated from propolis of hives from Cuncumen. This is the first report on propolis composition of an arid and a Mediterranean type climate area.

PMID: 11371019 [PubMed - indexed for MEDLINE]


88: Mutat Res. 2001 May;488(2):135-50.

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Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate.

Heo MY, Sohn SJ, Au WW.

College of Pharmacy, Kangwon National University, Chunchon 200, South Korea. h0858my@hanmail.net

Flavonoids are polyphenolic compounds that are present in plants. They have been shown to possess a variety of biological activities at non-toxic concentrations in organisms. Galangin, a member of the flavonol class of flavonoid, is present in high concentrations in medicinal plants (e.g. Alpinia officinarum) and propolis, a natural beehive product. Results from in vitro and in vivo studies indicate that galangin with anti-oxidative and free radical scavenging activities is capable of modulating enzyme activities and suppressing the genotoxicity of chemicals. These activities will be discussed in this review. Based on our review, galangin may be a promising candidate for cancer chemoprevention.

Publication Types:

       Review


PMID: 11344041 [PubMed - indexed for MEDLINE]


89: In Vivo. 2001 Jan-Feb;15(1):17-23.

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Diverse biological activities of healthy foods.

Kobayashi N, Unten S, Kakuta H, Komatsu N, Fujimaki M, Satoh K, Aratsu C, Nakashima H, Kikuchi H, Ochiai K, Sakagami H.

Fujimi Bee House, Shiki, Saitama, Japan.

Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.

PMID: 11286123 [PubMed - indexed for MEDLINE]


90: Anticancer Drugs. 2001 Feb;12(2):143-9.

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The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells.

Chen YJ, Shiao MS, Wang SY.

Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidation and tumor cell cytotoxicity. We examined the type of cell death in human leukemic HL-60 cells after CAPE treatment in order to elucidate the relationship between CAPE-induced alterations of the redox state and apoptosis. CAPE treatment (6 microg/ml) resulted in marked growth inhibition up to 70.3+/-4.0% at day 2. This inhibition was partially blocked by pretreatment with N-acetyl-L-cycteine (NAC). Agarose gel electrophoresis showed evident DNA fragmentation after CAPE treatment. CAPE induced a significant decrease in mitochondrial transmembrane potential to about half of the untreated level after 6 h and a rapid depletion of intracellular glutathione (GSH) down to 41.7+/-6.0% after 1 h. Pretreatment of HL-60 cells with NAC reversed the GSH depletion and partially rescued cells from CAPE-induced apoptosis. With regard to intracellular reactive oxygen species, CAPE caused a fast and profound scavenging of H202 (19% of untreated cells after a 2-h treatment) but not of superoxide anion. These results suggest that apoptosis induced by CAPE is associated with mitochondrial dysfunction, GSH depletion and selective scavenging of H2O2 in human leukemic HL-60 cells.

PMID: 11261888 [PubMed - indexed for MEDLINE]


91: Urol Res. 2000 Dec;28(6):360-3.

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Testicular nitric oxide levels after unilateral testicular torsion/detorsion in rats pretreated with caffeic acid phenethyl ester.

Koltuksuz U, Irmak MK, Karaman A, Uz E, Var A, Ozyurt H, Akyol O.

Department of Pediatric Surgery, Inonu University, Faculty of Medicine, Malatya, Turkey. ukoltuksuz@inonu.edu.tr

Nitric oxide (NO) plays an important role in modulating blood flow in normal and in several pathological conditions, and its levels seem to change with ischemia-reperfusion injuries. Caffeic acid phenethyl ester (CAPE), an active component of propolis, exhibits antioxidant properties. This experimental study was designed to determine the changes in NO levels and the effect of CAPE on NO levels after testicular torsion/ detorsion in rats. Thirty-five adult male albino rats were divided into four groups: sham operation (n = 8), torsion (n = 9), saline/detorsion (n = 9), and CAPE/detorsion (n = 9). Rats in the sham operation group were killed after the testes were handled without torsion. Rats in the torsion group were killed after 720 degrees clockwise testicular torsion for 2 h. CAPE was administered 30 min before detorsion in the CAPE/detorsion group and saline was administered in the saline/detorsion group. After 4 h of testicular detorsion in both of these groups, the rats were killed and bilateral orchiectomy was performed to determine the tissue levels of NO. The level of NO in the torsion group (113.77 +/- 33.18 nmol/g protein) was significantly higher than that of the sham operation group (64.53 +/- 29.64 nmol/g protein). In the saline/detorsion group, the NO level (31.26 +/- 12.58 nmol/g protein) was significantly lower than in the torsion and sham operation groups. CAPE administration in the CAPE/detorsion group seemed to raise the NO level (72.63 +/- 23.87 nmol/g protein) above the level of the sham operation group. Contralateral testes were not affected by the torsion/detorsion processes performed on the ipsilateral testes. These results show that NO levels increase with torsion and decrease with detorsion. CAPE administration seems to increase tissue NO levels and this may be important for protecting the testes from torsion/detorsion injuries.

PMID: 11221913 [PubMed - indexed for MEDLINE]


92: J Ethnopharmacol. 2000 Sep;72(1-2):239-46.

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Cytotoxic, hepatoprotective and free radical scavenging effects of propolis from Brazil, Peru, the Netherlands and China.

Banskota AH, Tezuka Y, Adnyana IK, Midorikawa K, Matsushige K, Message D, Huertas AA, Kadota S.

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

Propolis is a resinous hive product collected by honeybees from various plant sources. The composition of the propolis depends upon the time, vegetation and the area of collection. Thus, quality evaluation of the propolis is important, before use in food and beverages. For this propose three different biological activities were carried out, i.e. 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, cytotoxicity and hepatoprotective activity, of MeOH and water extracts of nine different propolis from Brazil, Peru, the Netherlands and China. The results showed that water extracts of six Brazilian and a Chinese propolis possessed stronger DPPH free radical scavenging activity than the corresponding MeOH extract, whereas in the case of Netherlands and Peruvian propolis MeOH extract exhibited stronger DPPH free radical scavenging activity. The MeOH extracts of all propolis possessed stronger cytotoxicity than the corresponding water extract towards murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cells. The result of hepatoprotective activity of Brazilian propolis on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes were found in accordance with the grade set up by beekeepers in Brazil.

PMID: 10967477 [PubMed - indexed for MEDLINE]


93: J Ethnopharmacol. 2000 Jul;71(1-2):109-14.

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Comparison of the free radical-scavenging activity of propolis from several regions of Argentina.

Moreno MI, Isla MI, Sampietro AR, Vattuone MA.

Catedra de Fitoquimica, Instituto de Estudios Vegetales, Facultad de Bioquimica, Quimica y Farmacia, Universidad Nacional de Tucuman, Ayacucho 461, 4000, San Miguel de Tucuman, Argentina.

Propolis is extensively used in Argentine folk medicine. Alcoholic extracts of propolis from different regions of Argentina were prepared. The extracts were analysed for the determination of total flavonoid content (from 13.3 to 42.6 mg/g of propolis) by using the aluminum nitrate method, UV spectrophotometry and thin layer chromatography. All of them contained high total flavonoid content. It was also observed that all samples of ethanolic extracts of propolis showed free radical-scavenging activity in terms of scavenging of the radical DPPH but the highest activities were found for samples from Tucuman and Santiago del Estero. In all cases with 20 microg/ml of soluble principles, the percentage of DPPH degradation was different (Banda Oeste: 67.5%; Veronica: 45%; Forres: 35%; Saenz Pena: 20% and Juan Jose Castelli: 55%). These results may justify their use as a source of natural antioxidants.

PMID: 10904153 [PubMed - indexed for MEDLINE]


94: J Agric Food Chem. 2000 May;48(5):1462-5.

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In vivo antioxidative activity of propolis evaluated by the interaction with vitamins C and E and the level of lipid hydroperoxides in rats.

Sun F, Hayami S, Haruna S, Ogiri Y, Tanaka K, Yamada Y, Ikeda K, Yamada H, Sugimoto H, Kawai N, Kojo S.

Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.

In vivo antioxidative activity of propolis was evaluated on the basis of ameliorative effects on the oxidative stress induced by vitamin E deficiency in rats. The control group was fed vitamin E-deficient diet, and the propolis group was fed vitamin E-deficient diet supplemented with 1% of propolis for 4 and 8 weeks. Comparisons were made in tissue concentrations of vitamin C, vitamin E, and lipid hydroperoxides between these groups. No significant difference was observed in tissue vitamin E concentration between these groups after both 4 and 8 weeks. After 4 weeks, the plasma vitamin C concentration of the propolis group was significantly higher than that of the control group. After 8 weeks, the tissue concentrations of vitamin C in the kidney, stomach, small intestine, and large intestine of the propolis group were significantly higher than those of the control group. These results suggest that some components of propolis are absorbed to circulate in the blood and behave as a hydrophilic antioxidant that saves vitamin C. The concentration of lipid hydroperoxides in the large intestine of the propolis group was significantly lower than that of the control group after 8 weeks. These results suggest that propolis exerts its antioxidative effect where it is assumed to accumulate, such as on the kidney, where it is excreted, and on the gastrointestinal tract, where propolis influences these tissues even from the outside of the cell.

PMID: 10820043 [PubMed - indexed for MEDLINE]


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

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

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

Institute of Pharmaceutical Chemistry, University of Heidelberg, Germany.

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

PMID: 10800636 [PubMed - indexed for MEDLINE]


96: Toxicology. 1999 Dec 6;139(3):219-32.

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Effects of some probable antioxidants on selenite-induced cataract formation and oxidative stress-related parameters in rats.

Orhan H, Marol S, Hepsen IF, Sahin G.

Toxicology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.

The effect of several natural and synthetic compounds on selenite-induced cataract was investigated in rat pups. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were carried out in the lens, erythrocyte and plasma. The results showed that propolis, diclofenac, vitamin C (Vit-C) and quercetin prevented cataract formation to the extent of 70, 60, 58.4, and 40%, respectively. Standardized extract of Ginkgo biloba (Egb 761) did not affect the cataract formation. Selenite treatment caused a significant decrease in the activity of erythrocyte SOD. This was accompanied by a simultaneous increase in the levels of MDA either in lens and in plasma. A significant increase was shown in erythrocyte GST (substrate ethacrynic acid; eaa), and GPx activities and lens GST (substrate chlorodinitro benzene; cdnb) activity. Antioxidant treatment caused significant changes in enzyme activities and MDA levels. There was no effect of selenite and antioxidants on total body weight increase during the course of the study. Blood parameters did not correlate to lens parameters following selenite treatment. Our results suggest that antioxidant supplementation following selenite exposure may prevent the cataract formation and may enhance antioxidant defence of blood and lens.

PMID: 10647922 [PubMed - indexed for MEDLINE]


97: Neoplasma. 1999;46(4):231-6.

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Separation of structurally related flavonoids by GC/MS technique and determination of their polarographic parameters and potential carcinogenicity.

Novotny L, Vachalkova A, Al-Nakib T, Mohanna N, Vesela D, Suchy V.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, Safat.

The present study deals with the investigation of the naturally occurring derivatives of the benzo[b]pyran-4-one - flavonoids - chrysin, tectochrysin and galangin, and with the effect of minor changes in their chemical structure on their separation using GC/MS. In the relation to their close chemical structure, their basic polarographic parameters were also investigated. Their potential carcinogenicity index tg alpha was determined by DC polarography experiments in the presence of alpha-lipoic acid. The tg alpha values for chrysin, tectochrysin and galangin were all under 0.180. This indicates a very minor carcinogenic potential that does not prevent the use of the investigated flavonoids in human.

PMID: 10613603 [PubMed - indexed for MEDLINE]


98: Eur J Cardiothorac Surg. 1999 Oct;16(4):458-63.

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The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits.

Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O.

Department of Neurology, Inonu University, Turgut Ozal Medical Center, Malatya, Turkey. atillai@hotmail.com

OBJECTIVE: Oxygen-derived free radicals have been implicated in the pathogenesis of spinal cord neuronal injury after both trauma and ischemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. This experimental study was designed to determine the effect of CAPE on ischemia-reperfusion of spinal cord in rabbits. METHODS: Forty-one New Zealand white rabbits were used in the study. The animals undergone aortic occlusion were divided into three groups each consisting of 11 rabbits: methylprednisolone (MP), CAPE, and control. CAPE 10 micromol/kg, methyl prednisolone (MP) 30 mg/kg or similar dose saline were injected intraperitoneally before surgical intervention. Animals were subjected to 21 min of cross-clamp time. At the end of occlusion time, the clamps were removed and restoration of the blood flow was verified visually. Animals in sham group (n = 8) underwent a surgical procedure similar to the other groups but the aorta was not occluded. Neurological status was scored by assessment of hindlimb motor function deficit. RESULTS: The scores in CAPE group was different from control groups at 48 h (3.91+/-0.5 vs. 2.91+/-0.7; P = 0.0013). Spinal cord specimens were obtained to determine the tissue levels of malondialdehyde, superoxide dismutase, catalase, and histological changes. Malondialdehyde levels in control group were increased significantly when compared to sham group (124.22+/-24.36 and 41.92+/-10.08 nmol/g wet tissue, P = 0.0003). MDA levels in the CAPE group were lower than MP group and differences between the two groups were statistically significant (56.77+/-15.265 and 107.74+/-19.31 nmol/g wet tissue, P = 0.0001). We did not observe additional tissue injury in CAPE group when compared to control group. SOD and CAT activities were not concordant in all the groups. CONCLUSIONS: These results suggest that CAPE may be an available agent to protect the spinal cord from ischemia-reperfusion injury.

PMID: 10571095 [PubMed - indexed for MEDLINE]


99: J Pediatr Surg. 1999 Oct;34(10):1458-62.

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Caffeic acid phenethyl ester prevents intestinal reperfusion injury in rats.

Koltuksuz U, Ozen S, Uz E, Aydinc M, Karaman A, Gultek A, Akyol O, Gursoy MH, Aydin E.

Department of Pediatric Surgery, Inonu University, Medical Faculty, Malatya, Turkey.

BACKGROUND/PURPOSE: Ischemia-reperfusion injury is encountered frequently in conditions that diminish intestinal blood flow. Caffeic acid phenethyl ester (CAPE), which is a specific component of the honeybee hive product propolis, exhibits potential antioxidant properties. This experimental study was designed to determine the effect of CAPE on ischemia-reperfusion injury in rat intestine. METHODS: Fifty rats were divided into 5 groups; sham (SH), saline ischemia (SI), saline reperfusion (SR), CAPE ischemia (CI), and CAPE reperfusion (CR). Either CAPE, 10 micromol/kg, or saline was administered intraperitoneally 30 minutes before ischemia. Intestinal ischemia for 30 minutes and reperfusion for 60 minutes were applied. Ileum specimens were obtained to determine the tissue levels of malondialdehyde, superoxide dismutase, catalase, and histological changes. RESULTS: Malondialdehyde levels in the CR group did not increase after reperfusion when compared with the CI group. However, statistically significant differences were observed between the SR and SI groups. Additional mucosal injury in the CR group when compared with the CI group was not observed. Whereas, there was a statistically significant increase in mucosal injury in the SR group. Reperfusion did not cause further injuries through both biochemical and histological parameters in the CR group. CONCLUSIONS: Results of this study showed that prophylactic administration of CAPE in ischemic condition prevents reperfusion injuries by eliminating oxygen radicals and inhibiting polymorphonuclear leukocyte infiltration. CAPE may be useful in combating the diseases of oxidative stress.

PMID: 10549747 [PubMed - indexed for MEDLINE]


100: Ophthalmic Res. 1999;31(6):426-31.

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Topically applied water extract of propolis to suppress corneal neovascularization in rabbits.

Hepsen IF, Er H, Cekic O.

Department of Ophthalmology, Turgut Ozal Medical Center, University of Inonu, Malatya, Turkey. ifh@aidata.com.tr

PURPOSE: Propolis, a natural honey bee hive product, has anti-inflammatory and antioxidative properties. We aimed to assess the possible contribution of topically applied propolis to the suppression of corneal neovascularization (CNV). METHODS: The effect of a water extract of propolis (WEP) 1% drops (group 1) in comparison with dexamethasone 0.1% (group 2) and saline (group 3) on CNV was tested in rabbit corneas injured by silver nitrate cauterization. The extent of CNV was quantitated as the area of CNV and the percent area of CNV for each cornea of the three groups (12 right eyes per group) in the first week of the treatment. The mean percent CNV was used for statistical analysis. RESULTS: The corneas treated with the topical WEP 1% had an almost equal percent CNV as compared with the corneas treated with topical dexamethasone 0.1% and had less percent CNV than the control eyes. The quantitative analysis in groups 1, 2 and 3 revealed that the mean percent CNV was 41.0 +/- 14.1, 39.4 +/- 11.0 and 56.9 +/- 18.4, respectively. The differences between both groups 1 and 3 as well as groups 2 and 3 were statistically significant (p = 0.02 and p = 0.01, respectively), whereas the difference between groups 1 and 2 was not significant (p = 0.86). CONCLUSIONS: The topical application of a WEP 1% has an inhibitory effect on CNV in the rabbit's cornea. The inhibitory effect of propolis was shown to be comparable to that of topical dexamethasone 0.1%, a potent inhibitor of angiogenesis. We suggest that the effect of propolis may partially be due to its inhibitory effect on the activity of both cyclo-oxygenase and lipo-oxygenase.

PMID: 10474071 [PubMed - indexed for MEDLINE]


101: Z Naturforsch [C]. 1997 Nov-Dec;52(11-12):828-33.

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Potent free radical scavenging activity of propol isolated from Brazilian propolis.

Basnet P, Matsuno T, Neidlein R.

Pharmazeutisch-Chemisches Institut, Universitat Heidelberg, Germany.

We evaluated free radical scavenging activity of the water, methanol and chloroform extracts of propolis in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and xanthine-xanthine oxidase (XOD) generated superoxide anion assay systems. The free radical scavenging activity guided fractionation and chemical analysis led to the isolation of a new compound, propol (3-[4-hydroxy-3-(3-oxo-but-1-enyl)-phenyl]-acrylic acid) from the water extract, which was more potent than most common antioxidants such as vitamin C and vitamin E (alpha-tocopherol) in these assay systems.

PMID: 9463940 [PubMed - indexed for MEDLINE]


102: Cancer Res. 1997 Feb 1;57(3):440-6.

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Caffeic acid phenethyl ester stimulates human antioxidant response element-mediated expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene.

Jaiswal AK, Venugopal R, Mucha J, Carothers AM, Grunberger D.

Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant derived from the propolis of honeybee hives. CAPE was shown to inhibit the formation of intracellular hydrogen peroxide and oxidized bases in DNA of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated HeLa cells and was also found to induce a redox change that correlated with differential growth effects in transformed cells but not the nontumorigenic parental ones. Mediated via the electrophile or human antioxidant response element (hARE), induction of the expression of NAD(P)H quinone oxidoreductase (NQO1) and glutathione S-transferase Ya subunit genes by certain phenolic antioxidants has been correlated with the chemopreventive properties of these agents. Here, we determined by Northern analysis that CAPE treatment of hepatoma cells stimulates NQO1 gene expression in cultured human hepatoma cells (HepG2), and we characterized the effects of CAPE treatment on the expression of a reporter gene either containing or lacking the hARE or carrying a mutant version of this element in rodent hepatoma (Hepa-1) transfectants. A dose-dependent transactivation of human hARE-mediated chloramphenicol acetyltransferase (cat) gene expression was observed upon treatments of the Hepa-1 transfectants with TPA, a known inducer, as well as with CAPE. The combined treatments resulted in an apparent additive stimulation of the reporter expression. To learn whether this activation of cat gene expression was effected by protein kinase C in CAPE-treated cells, a comparison was made of cat gene activity after addition of calphostin, a protein kinase C inhibitor. Calphostin reduced the cat gene induction by TPA but not by CAPE, suggesting that stimulation of gene expression in this system by these agents proceeds via distinct mechanisms. Band-shift experiments to examine binding of transactivator proteins from nuclear extracts of treated and untreated cells to a hARE DNA probe showed that TPA exposure increased the binding level. In contrast, binding of factors to this probe was inhibited after either in vivo treatment of cells with CAPE or in vitro addition of this compound to the nuclear extract. In view of the clear stimulation by CAPE of gene expression mediated by hARE, possible explanations of this result are discussed.

PMID: 9012471 [PubMed - indexed for MEDLINE]


103: Pharmacol Res. 1997 Jan;35(1):1-4.

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Effects of Cuban red propolis on galactosamine-induced hepatitis in rats.

Rodriguez S, Ancheta O, Ramos ME, Remirez D, Rojas E, Gonzalez R.

Electron Microscopy Laboratory, National Center for Scientific Research, Havana, Cuba.

Using transmission electron microscopy and biochemical analysis, the effect of cuban red propolis against hepatitis induced by 1,000 mg kg-1 of galactosamine in rats was studied. An ethanolic extract of propolis was prepared and it was given to rats at doses of 10, 50 and 100 mg kg-1, 30 min before the hepatotoxin. Propolis extract prevented hepatocytes alterations induced by galactosamine. It was mainly seen in rough endoplasmic reticulum, Golgi complex, nucleus and plasma membrane of hepatocytes. Propolis extract induced reversion of the increased activity of alanine aminotransferase and malondialdehyde concentration in the serum of rats treated with galactosamine. The probable role of antioxidant activity of propolis in the prevention of hepatitis is discussed in this paper.

PMID: 9149308 [PubMed - indexed for MEDLINE]


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

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

Mirzoeva OK, Calder PC.

Department of Biochemistry, University of Oxford, UK.

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

PMID: 9014224 [PubMed - indexed for MEDLINE]


105: Contact Dermatitis. 1996 Sep;35(3):184-5.

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Photodermatitis from plant derivatives in topical and oral medicaments.

Fernandez de Corres L, Diez JM, Audicana M, Garcia M, Munoz D, Fernandez E, Etxenagusia M.

Servicio de Alergologia, Hospital Santiago Apostol, Spain.

Publication Types:

       Case Reports


PMID: 8930489 [PubMed - indexed for MEDLINE]


106: Drugs Exp Clin Res. 1996;22(6):309-16.

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The protective effect of aqueous propolis extract on isolated rat hepatocytes against carbon tetrachloride toxicity.

Mahran LG, el-Khatib AS, Agha AM, Khayyal MT.

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

The protective effect of honeybee aqueous propolis extract (APE) against the hepatotoxicity of carbon tetrachloride was investigated using isolated liver-cell suspensions as the experimental model. Various concentrations of the extract were preincubated with the hepatocyte suspensions for 30 min before being subjected to the hepatotoxin for a further 30 min. The hepatocyte toxicity was assessed using three parameters, namely, the release of lactate dehydrogenase, the formation of lipid peroxides and the depletion of intracellular reduced glutathione. It was found that a dose-related protection against the induced cell injury was conferred by APE as evidenced by its inhibitory influence on the changes induced by CCl4 on the measured parameters. The hepatocyte protective effect of APE is probably a result of its antioxidant and free-radical-scavenging properties which in turn help to maintain the intracellular level of reduced glutathione.

PMID: 9034757 [PubMed - indexed for MEDLINE]


107: Arch Med Res. 1996 Autumn;27(3):285-9.

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Histopathological evaluation on the effect of red propolis on liver damage induced by CCl4 in rats.

Merino N, Gonzalez R, Gonzalez A, Remirez D.

Departamento de Farmacologia y Toxicologia, Centro Nacional de Investigaciones Cientificas, Havana, Cuba.

A histopathological evaluation was performed on liver of rats treated with carbon tetrachloride (CCl4) and 25,50 and 100 mg/kg of Cuban red propolis (RP) extract. Additionally, alanine aminotransferase (ALT) in serum and liver triglycerides were determined in all animals. The morphometric study included the count of ballooned cells at the zone III of the Rappaport acini and the assessment of a software program to estimate the extension of steatosis area. A significant reduction of ballooned cells count in liver was observed at three dose levels of RP extract with respect to rats treated only with CCl4. Also, a certain reduction of steatosis degree as well as decreased concentration of liver triglycerides and ALT activity were found in three groups of rats treated with RP extract and CCl4 in relation to those treated with the hepatotoxin. Taken together, the histopathological and biochemical findings show hepatoprotective effects of RP extract in CCl4-induced liver damage in rats, probably due to the antioxidant effect of RP.

PMID: 8854383 [PubMed - indexed for MEDLINE]


108: Exp Mol Pathol. 1995 Jun;62(3):190-8.

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Propolis protects against doxorubicin-induced myocardiopathy in rats.

Chopra S, Pillai KK, Husain SZ, Giri DK.

Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India.

Propolis (bee glue) is one of the major hive products of bees and is rich in flavonoids, which are known for antioxidant activities. Doxorubicin-induced myocardiopathy is the consequence of oxidative stress through the mediation of free radicals. The effect of intraperitoneal administration of propolis (50 and 100 mg/kg) was studied on cardiomyopathy produced by doxorubicin (10 mg/kg, i.v.) in rats. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), blood and tissue glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in heart were estimated to assess the status of heart muscle. An elevation of the levels of CK, AST, GSH, and TBARS was observed following doxorubicin treatment. Parallel experiments with a pretreatment of propolis significantly reduced the levels of these parameters . Biochemical observations were supplemented by histopathological examination of heart sections. The protective effect of propolis was compared with that of rutin, a known cardioprotective flavonoid. The study demonstrates the cardioprotective effect of propolis in doxorubicin-induced experimental cardiotoxicity.

PMID: 8612723 [PubMed - indexed for MEDLINE]


109: Free Radic Biol Med. 1995 May;18(5):901-8.

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Redox intermediates of flavonoids and caffeic acid esters from propolis: an EPR spectroscopy and cyclic voltammetry study.

Rapta P, Misik V, Stasko A, Vrabel I.

Faculty of Chemistry, Slovak Technical University, Bratislava, Slovak Republic.

The redox properties of flavonoids: chrysin (1), tectochrysin (2), galangin (3), isalpinin (4), pinostrobin (5), pinobanksin (6), pinobanksin-3-acetate (7), and of caffeic acid ester (8) and diacetylcaffeic acid ester (9), all isolated from propolis, were investigated by cyclic voltammetry in acetonitrile. The choice of aprotic solvent lowered the reactivity of the radical intermediates and made possible to identify redox steps and intermediates not detected so far. The oxidation potentials (vs. saturated calomel electrode) of the investigated compounds were in the region of 1.5 V for 3 and 4; 1.9 V for 1, 2, and 5; 2.0 V for 6 and 7; 1.29 V for 8; and 2.3 V for 9. These oxidation potentials were mainly influenced by the presence of a double bond in 2,3-position and substituent R1 in position 3. Comparison with our earlier data revealed that flavonoids, 1-4, and caffeic acid ester 8 with lower oxidation potentials showed the maximal lipid antioxidant activity, whereas those with higher potentials (5, 6, 7, and 9) are less active. On reduction of 1-9 several one-electron-steps were typically observed in the potential regions: -1.5 V, -1.8 V, and -2 V. where in simultaneous EPR experiments anion radicals of 1 and 3 were observed with the center of unpaired spin density on ring A. Upon oxidation of flavonoids 1-4 carbonyl carbon-centered radicals, .C(O)R, were identified as consecutive products using the EPR spin trapping technique.

PMID: 7797098 [PubMed - indexed for MEDLINE]


110: Bioorg Khim. 1995 Feb;21(2):143-51.

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[Lipophilic derivatives of caffeic acid as lipoxygenase inhibitors with antioxidant properties]

[Article in Russian]

Mirzoeva OK, Sud'ina GF, Pushkareva MA, Korshunova GA, Sumbatian NV, Varfolomeev SD.

We have prepared two lipophilic derivatives of caffeic acid at the carboxylic function--caffeic acid phenethyl ester, an active component of propolis, and N,N'-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)-isourea. Both substances inhibit barley 5-lipoxygenase and soybean 15-lipoxygenase at micromolar concentrations. The inhibition is uncompetitive, dose-dependent and reversible. The caffeic acid derivatives also exhibit antioxidant properties and at a concentration 5-10 microM completely block the production of the reactive oxygen species in human neutrophils and in the cell-free xanthine/xanthine oxidase system.

PMID: 7538294 [PubMed - indexed for MEDLINE]


111: Lik Sprava. 1995 Jan-Feb;(1-2):68-70.

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[The indices of the antioxidant system and the status of the cerebral blood supply in patients with an ischemic stroke on apitherapy]

[Article in Ukrainian]

Samoliuk VA.

It has been established that the use of apitherapy (pollen and propolis) to treat patients with ischemic insults leads to deeper positive shifts in indices of the antioxidant system and brain blood supply. This, in its turn, makes for rapid and complete restoration of disturbed and lost functions of the patients' organism.

PMID: 7483551 [PubMed - indexed for MEDLINE]


112: J Ethnopharmacol. 1994 Jan;41(1-2):9-13.

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Scavenging action of propolis extract against oxygen radicals.

Pascual C, Gonzalez R, Torricella RG.

National Center for Scientific Research, Clinical Biochemistry Department, Playa, La Habana, Cuba.

The ethanolic extracts of two types of cuban propolis (R and P) showed a similar manner of scavenging action against different species of oxygen radicals which were generated by specific chemical reactions. Chemiluminescence produced by superoxide generated from the xanthine-xanthine oxidase reaction was 50% inhibited by approximately 5 micrograms/ml of propolis R and 9.5 micrograms/ml of propolis P and by catechin (0.15 micrograms/ml) and superoxide dismutase (72 ng/ml). Alkoxy radical scavenging effect was similar to that produced by 0.11 micrograms/ml of alpha-tocopherol: inhibition of chemiluminescence by 50% was caused by approximately 0.6 micrograms/ml of both propolis preparations. The results indicate that the antioxidative properties of both propolis could be attributed to their free radical scavenging activity against alkoxy radicals and to a lesser degree against superoxide.

PMID: 8170165 [PubMed - indexed for MEDLINE]


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

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

Strehl E, Volpert R, Elstner EF.

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

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

PMID: 8148008 [PubMed - indexed for MEDLINE]


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

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Biochemical activities of propolis extracts. II. Photodynamic activities.

Volpert R, Elstner EF.

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

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

PMID: 8297423 [PubMed - indexed for MEDLINE]


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

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

Volpert R, Elstner EF.

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

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

PMID: 8297422 [PubMed - indexed for MEDLINE]


116: Cancer Res. 1993 Sep 15;53(18):4182-8.

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Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon.

Rao CV, Desai D, Simi B, Kulkarni N, Amin S, Reddy BS.

Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595.

Previous work from this laboratory established that caffeic acid esters, present in the propolis of honey bee hives, are potent inhibitors of human colon tumor cell growth, suggesting that these compounds may possess antitumor activity against colon carcinogenesis. The present study was designed to investigate (a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate (PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine protein kinase (TPK), and arachidonic acid metabolism in liver and colonic mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate (PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC, and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon of F344 rats. At 5 weeks of age, groups of animals were fed diets containing 600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF study). Two weeks later, all animals except the vehicle-treated groups were given s.c. injections of AOM, once weekly for 2 weeks. The animals intended for the biochemical study were sacrificed 5 days later and colonic mucosa and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites. The animals intended for the ACF study were sacrificed 9 weeks later and analyzed for ACF in the colon. The results indicate that the PEC diet significantly inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities in liver and colon. The PEC diet significantly (P < 0.001) suppressed the AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S)-HETEs and a significant (P < 0.001) effect on colonic TPK activity. However, the MC and PEC diets showed no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro study, caffeic acid and MC showed inhibitory effects on HETE formation only at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC (81%). The results of the present study indicate that PEC, PEMC, and PEDMC, present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC, TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis.

PMID: 8364913 [PubMed - indexed for MEDLINE]


117: FEBS Lett. 1993 Aug 23;329(1-2):21-4.

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Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties.

Sud'ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD.

A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russian Federation.

Caffeic acid phenethyl ester, an active component of propolis extract, inhibits 5-lipoxygenase in the micromolar concentration range. The inhibition is of an uncompetitive type, i.e. the inhibitor binds to the enzyme-substrate complex but not to the free enzyme. Caffeic acid phenethyl ester also exhibits antioxidant properties. At a concentration of 10 microM, it completely blocks production of reactive oxygen species in human neutrophils and the xanthine/xanthine oxidase system.

PMID: 7689063 [PubMed - indexed for MEDLINE]


118: Rev Roum Virol. 1992 Jul-Dec;43(3-4):165-73.

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[The mechanisms of the antiherpetic action of aqueous propolis extracts. I. The antioxidant action on human fibroblast cultures]

[Article in French]

Dumitrescu M, Esanu V, Crisan I.

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

A redox state modulation model was worked out in human fibroblast cultures treated with oxidation stress inducing agents and a redox agent, virtually protecting cell against the stress. Quantification of the global redox changes in fibroblasts was done using the hemoglobin electronic spectrum, in the presence and in the absence of H2O2.

PMID: 1339205 [PubMed - indexed for MEDLINE]


119: Int J Radiat Biol. 1990 Mar;57(3):461-5.

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Free radical scavenging by ethanol extract of propolis.

Scheller S, Wilczok T, Imielski S, Krol W, Gabrys J, Shani J.

Department of Microbiology, Silesian School of Medicine, Zabrze-Rokitnica, Poland.

The free radical scavenging ability of an ethanolic extract of propolis (EEP) was demonstrated by electron spin resonance spectroscopy, when 2,2-diphenyl-1-picrylhydrazyl (DPPH) was treated with increasing concentrations of EEP. It was shown that the DPPH signal intensity was inversely related to the EEP concentration and to the reaction time. It is assumed that the ability of components in EEP to donate a hydrogen atom is responsible for the lowering of the DPPH-EEP signal, and reflect the anti-oxidative nature of EEP.

PMID: 1968939 [PubMed - indexed for MEDLINE]


120: Biochem Int. 1990;21(4):593-7.

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Anti-oxidant property of ethanolic extract of propolis (EEP) as evaluated by inhibiting the chemiluminescence oxidation of luminol.

Krol W, Czuba Z, Scheller S, Gabrys J, Grabiec S, Shani J.

Department of Microbiology, Silesian School of Medicine, Zabrze-Rokitnica Poland.

Ethanolic extract of propolis (EEP) has remarkable medical properties, including protection of mice against gamma irradiation. Its anti-oxidative effect has been attributed to its radical scavenging ability. This manuscript demonstrates the ability of increasing amounts of EEP to inhibit luminol-H2O2 chemiluminescence in vitro, and suggests that its anti-oxidative capacity is partly due to its high content of flavonoids.

PMID: 2241984 [PubMed - indexed for MEDLINE]


121: Z Naturforsch [C]. 1989 Nov-Dec;44(11-12):1049-52.

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The ability of ethanolic extract of propolis (EEP) to protect mice against gamma irradiation.

Scheller S, Gazda G, Krol W, Czuba Z, Zajusz A, Gabrys J, Shani J.

Department of Microbiology, Silesian School of Medicine, Zabrze-Rokitnica, Poland.

Ethanolic extract of propolis (EEP) was tested as a protective agent against gamma irradiation in mice. The mice were exposed to 6 Gy gamma irradiation from a 60Co source, and were treated intraperitoneally with EEP, administered before and after their irradiation. While the non-treated mice expired within 12 weeks, the mice that received a series of EEP treatments survived the irradiation, and their leucocyte count as well as their spleens' plaque-forming activity returned to normal. It is suggested that an antioxidant and a free radical scavenger in the EEP are responsible for the radiation protective effect of the extract of this natural product.

PMID: 2698623 [PubMed - indexed for MEDLINE]


122: Vopr Pitan. 1988 Jul-Aug;(4):68-70.

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[Vitamin E and propolis as antioxidants after excessive administration of polyunsaturated fatty acids]

[Article in Russian]

Okonenko LB, Aidarkhanov BB, Rakhmetova AA, Zhakisheva SSh, Iksymbaeva ZhS.

Polyunsaturated fatty acids included into animals' ration (10% of linethol) intensified lipid peroxidation and increased the activity of cathepsin D, an enzyme responsible for protein and lipid degradation in the cell. Vitamin E stabilized the impaired processes. Biologically active complex of propolis produced a similar effect, however, decreased protein synthesis and a tendency to animals' body mass increment have evidenced a more pronounced antioxidative action as compared to that of vitamin E.

PMID: 3232343 [PubMed - indexed for MEDLINE]


123: Agressologie. 1987 Sep;28(8):831-2.

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Biochemical effects of standardized propolis extract (SPE) and of silymarin on the liver of ethyl alcohol intoxicated rats.

Giurgea R, Rusu MA, Coprean D, Popescu H, Polinicencu C.

PMID: 3425824 [PubMed - indexed for MEDLINE]


124: Vopr Med Khim. 1986 May-Jun;32(3):45-8.

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[Propolis as an inhibitor of free radical lipid oxidation in salmonellosis]

[Article in Russian]

Okonenko LB.

Lipid peroxidation was activated in salmonellosis. Content of hydroperoxides and malonic dialdehyde was increased in mice liver tissue. At the same time, the activity of antioxidative enzymes was altered. Continuous administration of propolis stabilized lipid peroxidation, thus suggesting that the substance could be used as a drug in medicine.

PMID: 3523990 [PubMed - indexed for MEDLINE]