segunda-feira, 4 de maio de 2009

Própolis - Trabalhos Acadêmicos (PubMed e outros)


Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis.
Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan.Artepillin C was extracted from Brazilian propolis. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) has a molecular weight of 300.40 and possesses antibacterial activity. When artepillin C was applied to human and murine malignant tumor cells in vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth of tumor cells was clearly inhibited. The artepillin C was found to cause significant damage to solid tumor and leukemic cells by the MTT assay, DNA synthesis assay, and morphological observation in vitro. When xenografts of human tumor cells were transplanted into nude mice, the cytotoxic effects of artepillin C were most noticeable in carcinoma and malignant melanoma. Apoptosis, abortive mitosis, and massive necrosis combined were identified by histological observation after intratumor injection of 500 microg of artepillin C three times a week. In addition to suppression of tumor growth, there was an increase in the ratio of CD4/CD8 T cells, and in the total number of helper T cells. These findings indicate that artepillin C activates the immune system, and possesses direct antitumor activity.PMID: 9824373 [PubMed - indexed for MEDLINE]

Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient of Brazilian propolis.
Kimoto T, Aga M, Hino K, Koya-Miyata S, Yamamoto Y, Micallef MJ, Hanaya T, Arai S, Ikeda M, Kurimoto M.
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Fujisaki 675-1, Okayama 702-8006, Japan. C (3,5-diprenyl-4-hydroxycinnamic acid) is an active ingredient of Brazilian propolis that possesses anti-tumor activity. When Artepillin C was applied to human leukemia cell lines of different phenotypes, namely, lymphocytic leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), myeloid and monocytic leukemia and non-lymphoid non-myeloid leukemia cell lines in vitro, Artepillin C exhibited potent cytocidal effects and induced marked levels of apoptosis in all the cell lines. The most potent effects were observed in the T-cell lines. Apoptotic bodies and DNA fragmentation were induced in the cell lines after exposure to Artepillin C. DNA synthesis in the leukemia cells was clearly inhibited and disintegration of the cells was confirmed microscopically. Apoptosis of the leukemia cells may be partially associated with enhanced Fas antigen expression and loss of mitochondrial membrane potential. In contrast, although Artepillin C inhibited the growth of pokeweed mitogen (PWM)-stimulated normal blood lymphocytes, it was not cytocidal to normal unstimulated lymphocytes. These results suggested that Artepillin C, an active ingredient of Brazilian propolis, has anti-leukemic effects with limited inhibitory effects on normal lymphocytes.PMID: 11299738 [PubMed - indexed for MEDLINE]

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.Publication Types: PMID: 11734336 [PubMed - indexed for MEDLINE]

Immune activation and radioprotection by propolis.
Takagi Y, Choi IS, Yamashita T, Nakamura T, Suzuki I, Hasegawa T, Oshima M, Gu YH.
Graduate School of Health Science, Suzuka University of Medical Science 1001-1 Kishioka-cho, Suzuka-shi, Mie 510-0293, Japan.In this study, we focused on immune stimulation by Propolis, and examined changes in the effect of irradiation after Propolis administration. We also examined the radioprotective effect of Propolis by observing its effect on the immune system. The effect of immune activation by Propolis was investigated by measuring the total immunoglobulin (Ig) G and IgM. The radioprotective effect of immune activation by Propolis was investigated by measuring the T-lymphocyte subsets in the peripheral blood of mice following whole body irradiation. Compared with the control group, the IgG was significantly reduced in the Propolis group, indicating that Propolis suppressed IgG production. ELISA revealed that the amount of IgM in mouse serum was significantly higher in the Propolis group as compared with the control group, indicating that Propolis increased IgM production. The number of CD4-positive cells was increased only in the Propolis group. Likewise, the number of CD4-positive cells increased by 81% in the Propolis with irradiation group compared with the irradiation group alone. Compared with the control group, the Propolis group increased CD8-positive cells. Compared with the irradiation alone group, CD8-positive cells were decreased by Propolis with irradiation group. Propolis activated macrophages to stimulate interferon (IFN)-gamma production in association with the secondary activation of T-lymphocytes, resulting in a decrease in IgG and IgM production. Cytokines released from macrophages in mouse peripheral blood after Propolis administration activated helper T-cells to proliferate. In addition, activated macrophages in association with the secondary T-lymphocyte activation increased IFN-gamma production and stimulated proliferation of cytotoxic T-cells and suppressor T-cells, indicating the activation of cell-mediated immune responses.PMID: 15974482 [PubMed - indexed for MEDLINE]

Anti-AIDS agents. 48.(1) Anti-HIV activity of moronic acid derivatives and the new melliferone-related triterpenoid isolated from Brazilian propolis
Ito J, Chang FR, Wang HK, Park YK, Ikegaki M, Kilgore N, Lee KH.
Natural Products Laboratory, School of Pharmacy, University of North Carolina, NC 27599, USA.A new triterpenoid named melliferone (1), three known triterpenoids, moronic acid (2), anwuweizonic acid (3), and betulonic acid (4), and four known aromatic compounds (5-8) were isolated from Brazilian propolis and tested for anti-HIV activity in H9 lymphocytes. Moronic acid (2) showed significant anti-HIV activity (EC(50) <0.1>186) and was modified to develop more potent anti-AIDS agents.Publication Types:
PMID: 11678650 [PubMed - indexed for MEDLINE]

PM-3, a benzo-gamma-pyran derivative isolated from propolis, inhibits growth of MCF-7 human breast cancer cells.
Luo J, Soh JW, Xing WQ, Mao Y, Matsuno T, Weinstein IB.
Herbert Irving Comprehensive Cancer Center, Columbia Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties. Several components isolated from propolis have been shown to have anticancer activity. This study demonstrates that the compound PM-3 (3-[2-dimethyl-8-(3-methyl-2-butenyl)benzopyran]-6-propenoic acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7 human breast cancer cells. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Treatment of MCF-7 cells with PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein levels of cyclin D1 and cyclin E. PM-3 also inhibited the expression of cyclin D1 at the transcriptional level when examined in cyclin D1 promoter luciferase assays. Induction of apoptosis by PM-3 occurred within 48 hours after treatment of MCF-7 cells. The MCF-7 treated cells also displayed a decrease in the level of the estrogen receptor (ER) protein and inhibition of estrogen response element (ERE) promoter activity. Therefore, PM-3 merits further investigation with respect to breast cancer chemoprevention or therapy.Publication Types: PMID: 11497245 [PubMed - indexed for MEDLINE]

Protective action of propolis on the rat colon carcinogenesis.
Bazo AP, Rodrigues MA, Sforcin JM, de Camargo JL, Ribeiro LR, Salvadori DM.
Departamento de Patologia, Faculdade de Medicina, UNESP, Botucatu, São Paulo, Brazil.Propolis is a honeybee product with several biological and therapeutical properties. Its effect on the process of colon carcinogenesis and DNA damage were evaluated in the male Wistar rats using the aberrant crypt foci (ACF) assay and the comet assay, respectively. For both tests, animals were treated with the colon carcinogen 1,2 dimethylhydrazine (DMH, 40 mg/kg, s.c.) for 2 weeks (two injections/week) in order to induce both DNA damage and ACF. The animals were divided into groups that received propolis (ethanolic extract) at three different doses (10, 30, and 90 mg/kg b.w., by gavage), either simultaneously or after DMH treatment. For the comet assay, peripheral blood samples were collected 4 h after the last DMH treatment. All animals were sacrificed at the 5th week for evaluation of ACF. The results show that only the intermediate dose (30 mg/kg) of propolis, administered after DMH initiation, is significantly associated to a smaller number of aberrant crypts in the distal colon. No effect on DNA damage in peripheral blood cells, however, was verified by the comet assay. These data suggest that propolis has a protective influence on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, and probably exerts no protection against the initiation of carcinogenesis. Copyright 2002 Wiley-Liss, Inc.Publication Types:
PMID: 11948629 [PubMed - indexed for MEDLINE]

Effect of propolis extract on malignant cell transformation by moloney murine sarcoma virus.
Huleihel M, Ishano V.
The Institute for Applied Biosciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. aqueous extract of propolis was found to significantly inhibit NIH/3T3 cell malignant transformation by Moloney murine sarcoma virus (MuSV-124). The inhibitory effect of propolis extract was most effective when it was added 2 h before infection or at the time of infection. The continuous presence of propolis extract in the culture medium was essential for full prevention of malignant cell transformation. When treatment with propolis extract was terminated, five to ten days post-infection, there was a significant recovery in cell transformation. These results suggest that propolis extract inhibits a late step after provirus integration into the host genome. Addition of propolis extract after infection with MuSV significantly inhibited cell transformation. The inhibitory effect of propolis appeared to be the result of the inhibition of primary--not secondary--infections, since MuSV-124 yields a virus-nonproducing infection.PMID: 11676414 [PubMed - indexed for MEDLINE]

Preferential cytotoxicity to tumor cells of 3,5-diprenyl-4-hydroxycinnamic acid (artepillin C) isolated from propolis.
Matsuno T, Jung SK, Matsumoto Y, Saito M, Morikawa J.
National Institute of Health, Tokyo, Japan.A tumoricidal substance was isolated from Brazilian propolis as guided by cytotoxicity assay on HuH 13 (human hepatocellular carcinoma) cell and was characterized to be 3-[4-hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl]-2-propenoic acid (3,5-diprenyl-4-hydroxycinnamic acid (artepillin C)). It exhibited preferential cytotoxicity to tumor cells cultured in vitro. The cytotoxicity observed seemed to be partly attributable to apoptosis-like DNA fragmentation. The compound showed anti-tumor activity more effective than that of 5-fluorouracil to transplantable human tumor cell lines when tested on histoculture drug response assay system.PMID: 9413203 [PubMed - indexed for MEDLINE]

Hepatoprotective and anti-Helicobacter pylori activities of constituents from Brazilian propolis.
Banskota AH, Tezuka Y, Adnyana IK, Ishii E, Midorikawa K, Matsushige K, Kadota S.
Department of Natural Products Chemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.Propolis is a resinous hive product collected by honeybees from various plant sources. It is extensively used in food, beverage and in folk medicine for treating various ailments and reported to have broad spectrum of biological activities. The hepatoprotective activity of propolis and constituents from its MeOH extract belonging to various classes were tested on D-galactosamine (D-GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. The result indicated that hepatoprotective activity of alcoholic extract of tropical Brazilian propolis is mainly due to phenolic compounds including flavonoids. All the four isolated flavonoids possessed stronger inhibitory activity (IC50, < color="#ff0000">Link:

Effects of Apis mellifera propolis on the activities of streptococcal glucosyltransferases in solution and adsorbed onto saliva-coated hydroxyapatite. Koo H, Vacca Smith AM, Bowen WH, Rosalen PL, Cury JA, Park YK.
Faculty of Dentistry of Piracicaba, State University of Campinas, Piracicaba, Brazil. hyunkoobr@yahoo.comPropolis, a resinous hive product collected by Apis mellifera bees, has been used for thousands of years in folk medicine. Ethanolic extracts of propolis (EEP) have been shown to inhibit the activity of a mixture of crude glucosyltransferase (Gtf) enzymes in solution. These enzymes synthesize glucans from sucrose, which are important for the formation of pathogenic dental plaque. In the present study, the effects of propolis from two different regions of Brazil on the activity of separate, purified Gtf enzymes in solution and on the surface of saliva-coated hydroxyapatite (sHA) beads were evaluated. The EEP from Minas Gerais (MG; Southeastern Brazil) and Rio Grande do Sul (RS; Southern Brazil) were tested for their ability to inhibit the enzymes GtfB (synthesis of insoluble glucan), GtfC (insoluble/soluble glucan) and GtfD (soluble glucan). The effects of propolis on Gtf from Streptococcus sanguis (soluble glucan synthesis) was also explored. The EEP from both regions effectively inhibited the activity of all Gtfs in solution (75-95%) and on the surface of sHA beads (45-95%) at concentrations between 0.75 and 3.0 mg of propolis/ml. However, the two samples of propolis showed different levels of inhibition on each of the enzymes tested. In general, EEP RS demonstrated a significantly higher inhibitory activity on GtfB and C activities (both solution and surface assays) than EEP MG at concentrations between 0.047 and 0.187 mg/ml (p<0.05). color="#ff0000">Link:

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