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1: 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]

2: Phytother Res. 2003 Mar;17(3):250-3.

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The protective effects of Propolis on hepatic injury and its mechanism.

Seo KW, Park M, Song YJ, Kim SJ, Yoon KR.

Toxicology Department, National Institute of Toxicological Research, Korea Food and Drug Administration, 5 Nokbundong, Eunpyunggu, Seoul 122-020, Korea.

AbstractPropolis (PP) is a sticky substance that is collected from plants by honeybees. The purpose of this study was to investigate the protective effects of PP on hepatotoxicity induced by acetaminophen (AA, paracetamol) and the mechanism of its hepatoprotective effect. In rat hepatocyte culture, pretreatment with PP (1, 10, 100, 200 and 400 microg/mL, 24 h) significantly decreased the cytotoxicity of AA (0.5 mm) in a dose-dependent manner. In mice, pretreatment with PP (10 and 25 mg/kg, p.o., 7 days) also decreased the mortality and the incidence and severity of hepatic necrosis induced by AA (400 mg/kg, i.p.). After treatment with PP for 7 days, the hepatic enzyme activities of cytochrome P450 monooxygenases (P450s), UDP-glucuronyltransferase, phenolsulphotransferase (PST), glutathione S-transferase (GST) were measured in both rats and mice. In rats, PP (50 and 100 mg/kg, p.o.) decreased the activity of P4502E1, but significantly increased the activities of GST and PST. On the other hand, in mice treated with PP (10 and 25 mg/kg, p.o.), the activities of P4501A2, 2B1, 3A4 and 2E1 were dramatically inhibited, and the activity of PST was significantly enhanced. These results suggest that PP has a protective effect on hepatic injury, and that its effect may be explained by inhibition of phase I enzymes and induction of phase II enzymes. Copyright 2003 John Wiley & Sons, Ltd.

PMID: 12672155 [PubMed - indexed for MEDLINE]

3: 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]

4: Biol Pharm Bull. 1999 Nov;22(11):1237-9.

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Effect of propolis extract on D-galactosamine-induced hepatic injury in rats.

Sugimoto Y, Tarumi T, Kaneko Y, Isayama S, Kawai N, Sugimoto H, Yamada H, Kamei C.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.

The preventive effect of propolis extract on D-galactosamine-induced hepatic injury was examined in rats. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased at 24 h after intraperitoneal injection of D-galactosamine (400 mg/kg) in the animals. Propolis extract was administered orally three times in doses of 3 or 30 mg/kg at 18 h and 1 h before and 8 h after D-galactosamine injection. The extract itself and the vehicle alone (dextran) caused no significant changes in serum AST or ALT activities. Treatment with the extract dose-dependently prevented the increases in serum AST and ALT activities induced by D-galactosamine, and significant inhibition was observed at a dose of 30 mg/kg. These results suggested that propolis extract may have an ameliorating effect on hepatic dysfunction.

PMID: 10598035 [PubMed - indexed for MEDLINE]

5: 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]

6: 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]

7: Eksp Klin Farmakol. 1994 Jul-Aug;57(4):39-42.

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[The liver-protective properties of the pediatric drug form of propolis in animals of different age groups]

[Article in Russian]

Drogovoz SM, Tikhonov AI, Slyshkov VV, Sal'nikova SI.

The pharmacological activity of a pediatric formulation of the phenolic hydrophobic drug propolis was studied in the experiments on albino rats of various age with toxic liver damages of various duration and in acute hepatic ischemia. In all models of hepatic abnormalities, the drug was found to show antioxidative properties which were moderate (30-60%). In addition, there were improvements in hepatic secretion of bile, cholic acids, and cholesterol. On the other hand, the membrane-stabilizing effect of the drug was exerted in not all the tested models of hepatic damage.

PMID: 7950783 [PubMed - indexed for MEDLINE]

8: Virologie. 1980 Oct-Dec;31(4):273-8.

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Investigations concerning the action of serveral chemical and biological agents on HBsAg.

Morfei A, Burducea O, Neuman R, Cajal N, Copelovici Y, Crisan I.

Native and purified HBsAg preparations were subjected in vitro to the action of cetylpyridinium bromide (Bromocet), hibitan-chlorhexidine (Hibiscrub), chloramine B and propolis extract, at different concentrations and for various time intervals. The effect of these agents on the serological reactivity of HBsAg was tested by electroimmunodiffusion (EID) and radioimmunoassay (RIA). Chloramine B and the propolis extract had a significant inhibitory effect-ascertained by both EID and RIA - on purified HBsAg, but not on the native preparation. The inhibition exerted by Bromocet and Hibiscrub indicated by EID results was not confirmed by RIA.

PMID: 7257176 [PubMed - indexed for MEDLINE]