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Mariana Laundry De ,mesquita - One of the best experts on this subject based on the ideXlab platform.

  • Potencial antitumoral de substâncias isoladas de plantas do Cerrado brasileiro : estudos preliminares do mecanismo de ação da atividade citotóxica
    2010
    Co-Authors: Mariana Laundry De ,mesquita
    Abstract:

    O Câncer é uma doença, que atinge mais ou menos 200 tipos de células, caracterizada pelo desvio no controle da proliferação, diferenciação e morte celular, com multiplicação desordenada das células, podendo invadir órgãos e tecidos. As dificuldades encontradas no seu tratamento são a resistência medicamentosa, toxicidade, baixa especificidade, além da maioria das formulações serem injetáveis, pois são moléculas insolúveis em água, causando edemas e necrose. As substâncias de plantas do Cerrado podem constituir modelos interessantes para o desenvolvimento de novas moléculas anticancerígenas. Neste estudo foi realizada uma triagem com quatrocentos e doze extratos de plantas do bioma Cerrado sobre três linhagens celulares de câncer humano: MDA-MB- 435 (melanoma), HCT-8 (cólon), e SF-295 (glioblastoma). Como resultados, 28 extratos inibiram significativamente as células, a uma concentração de 50 µ g/mL, e tiveram seus valores de CI50 (concentração inibitória para 50% das células) sobre as células MDA-MB- 435, HCT-8, SF-295 e HL-60 (leucemia promielocítica) determinados. Os extratos que apresentaram CI50 < 20 µ g/mL, em no mínimo três linhagens, foram considerados muito ativos, dentre eles os extratos hexânicos da casca da raiz de Kielmeyera coriacea e Simarouba versicolor e o extrato diclorometânico das folhas de Schinus terebinthifolius var. radiannus. Estes extratos foram submetidos a estudo químico biomonitorado, e substâncias com atividade anticancerígena foram isoladas. Do extrato hexânico da casca da raiz de Simarouba versicolor obteve-se a glaucarubinona substância com atividade anticancerígena importante. O fracionamento químico do extrato diclorometânico de Schinus terebinthifolius var. radiannus resultou no isolamento de cinco compostos, em fase de elucidação estrutural, além de um alquil resorcinol isolado pela primeira vez desta espécie, e do beta-sitosterol. Do extrato hexânico da casca da raiz de Kielmeyera coriacea foi obtida uma mistura contendo o derivado da vitamina E, δ-tocotrienol e seu peróxido-dímero. Estudos de mecanismo de ação com essa mistura sobre a linhagem HL-60 foram conduzidos. A mistura demonstrou possuir efeito citotóxico e antiproliferativo sobre essas células, causando alterações no ciclo celular como inibição na síntese de DNA e indução de morte por apoptose e necrose, sendo dessa forma uma amostra promissora para a investigação da relação estrutura-atividade. _________________________________________________________________________________________ ABSTRACTCancer is an ailment that affects more or less 200 different types of cells. Its major characteristic is the lack of proliferation control, differentiation and apoptosis, with an uncontrolled multiplication of cells, with the ability of invading organs and tissues. There are many difficulties in the cancer treatment, with the most frequent being the drug resistance, toxicity and low specificity. As most of the molecules are water insoluble, the administration of the drug in the blood stream may cause edema and necrosis. The substances obtained from the Brazilian Cerrado plants are interesting models for the development of new anticancer molecules. The present study investigated the cytotoxic potential of 412 Cerrado plant extracts against three human cancer cell lines: MDA-MB-435 (melanoma), HCT-8 (colon) and SF-295 (glioblastome). Of the tested extracts, 28 demonstrated a substantial antiproliferative effect, inhibiting significantly the tumor cell proliferation at 50 μg/ml. Complete dose-response curves were generated and IC50 values (concentration causing 50% inhibition of parasite growth) were calculated for these extracts against four cell lines MDA-MB-435, HCT-8, SF-295 and HL-60 (Promielocitic Leukemia). The extracts that showed IC50 values < 20 µg/ml, in at least three cell lines were considered very actives. Among them, the hexane extracts of Kielmeyera coriacea and Simarouba versicolor root bark, and the dichloromethane extract of Schinus terebinthifolius var. raddianus leaves. These extracts were submitted to a bioassay-guided fractionation and anticancer substances were isolated. From the hexane extract of Simarouba versicolor root bark we isolated the glaucarubinone, a substance with remarked anticancer activity. The bioassay-guided fractionation of the dichloromethane extract of Schinus terebinthifolius var. raddianus leaves resulted in the isolation of five compounds, including an alkyl resorcinol obtained for the first time from this species, and beta-sytosterol. From the hexane extract of Kielmeyera coriacea root bark were obtained a mixture of the vitamin E derivative, δ-tocotrienol and its peroxydimer. This mixture showed antiproliferative and cytotoxic effects against the cells, through DNA synthesis inhibition and induction of cell death by apoptosis and necrosis. It is a promising sample to have its structure-activity relationship investigated

  • Potencial antitumoral de substâncias isoladas de plantas do Cerrado brasileiro : estudos preliminares do mecanismo de ação da atividade citotóxica
    2009
    Co-Authors: Mariana Laundry De ,mesquita
    Abstract:

    Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2009.O Câncer é uma doença, que atinge mais ou menos 200 tipos de células, caracterizada pelo desvio no controle da proliferação, diferenciação e morte celular, com multiplicação desordenada das células, podendo invadir órgãos e tecidos. As dificuldades encontradas no seu tratamento são a resistência medicamentosa, toxicidade, baixa especificidade, além da maioria das formulações serem injetáveis, pois são moléculas insolúveis em água, causando edemas e necrose. As substâncias de plantas do Cerrado podem constituir modelos interessantes para o desenvolvimento de novas moléculas anticancerígenas. Neste estudo foi realizada uma triagem com quatrocentos e doze extratos de plantas do bioma Cerrado sobre três linhagens celulares de câncer humano: MDA-MB- 435 (melanoma), HCT-8 (cólon), e SF-295 (glioblastoma). Como resultados, 28 extratos inibiram significativamente as células, a uma concentração de 50 µ g/mL, e tiveram seus valores de CI50 (concentração inibitória para 50% das células) sobre as células MDA-MB- 435, HCT-8, SF-295 e HL-60 (leucemia promielocítica) determinados. Os extratos que apresentaram CI50 < 20 µ g/mL, em no mínimo três linhagens, foram considerados muito ativos, dentre eles os extratos hexânicos da casca da raiz de Kielmeyera coriacea e Simarouba versicolor e o extrato diclorometânico das folhas de Schinus terebinthifolius var. radiannus. Estes extratos foram submetidos a estudo químico biomonitorado, e substâncias com atividade anticancerígena foram isoladas. Do extrato hexânico da casca da raiz de Simarouba versicolor obteve-se a glaucarubinona substância com atividade anticancerígena importante. O fracionamento químico do extrato diclorometânico de Schinus terebinthifolius var. radiannus resultou no isolamento de cinco compostos, em fase de elucidação estrutural, além de um alquil resorcinol isolado pela primeira vez desta espécie, e do beta-sitosterol. Do extrato hexânico da casca da raiz de Kielmeyera coriacea foi obtida uma mistura contendo o derivado da vitamina E, δ-tocotrienol e seu peróxido-dímero. Estudos de mecanismo de ação com essa mistura sobre a linhagem HL-60 foram conduzidos. A mistura demonstrou possuir efeito citotóxico e antiproliferativo sobre essas células, causando alterações no ciclo celular como inibição na síntese de DNA e indução de morte por apoptose e necrose, sendo dessa forma uma amostra promissora para a investigação da relação estrutura-atividade. _________________________________________________________________________________________ ABSTRACTCancer is an ailment that affects more or less 200 different types of cells. Its major characteristic is the lack of proliferation control, differentiation and apoptosis, with an uncontrolled multiplication of cells, with the ability of invading organs and tissues. There are many difficulties in the cancer treatment, with the most frequent being the drug resistance, toxicity and low specificity. As most of the molecules are water insoluble, the administration of the drug in the blood stream may cause edema and necrosis. The substances obtained from the Brazilian Cerrado plants are interesting models for the development of new anticancer molecules. The present study investigated the cytotoxic potential of 412 Cerrado plant extracts against three human cancer cell lines: MDA-MB-435 (melanoma), HCT-8 (colon) and SF-295 (glioblastome). Of the tested extracts, 28 demonstrated a substantial antiproliferative effect, inhibiting significantly the tumor cell proliferation at 50 μg/ml. Complete dose-response curves were generated and IC50 values (concentration causing 50% inhibition of parasite growth) were calculated for these extracts against four cell lines MDA-MB-435, HCT-8, SF-295 and HL-60 (Promielocitic Leukemia). The extracts that showed IC50 values < 20 µg/ml, in at least three cell lines were considered very actives. Among them, the hexane extracts of Kielmeyera coriacea and Simarouba versicolor root bark, and the dichloromethane extract of Schinus terebinthifolius var. raddianus leaves. These extracts were submitted to a bioassay-guided fractionation and anticancer substances were isolated. From the hexane extract of Simarouba versicolor root bark we isolated the glaucarubinone, a substance with remarked anticancer activity. The bioassay-guided fractionation of the dichloromethane extract of Schinus terebinthifolius var. raddianus leaves resulted in the isolation of five compounds, including an alkyl resorcinol obtained for the first time from this species, and beta-sytosterol. From the hexane extract of Kielmeyera coriacea root bark were obtained a mixture of the vitamin E derivative, δ-tocotrienol and its peroxydimer. This mixture showed antiproliferative and cytotoxic effects against the cells, through DNA synthesis inhibition and induction of cell death by apoptosis and necrosis. It is a promising sample to have its structure-activity relationship investigated

Ronald P Mensink - One of the best experts on this subject based on the ideXlab platform.

  • effects on the human serum lipoprotein profile of β glucan soy protein and isoflavones plant sterols and stanols garlic and tocotrienols
    Journal of Nutrition, 2002
    Co-Authors: Danielle A J M Kerckhoffs, Fred Brouns, Gerard Hornstra, Ronald P Mensink
    Abstract:

    The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile.

  • effects on the human serum lipoprotein profile of β glucan soy protein and isoflavones plant sterols and stanols garlic and tocotrienols
    Journal of Nutrition, 2002
    Co-Authors: Danielle A J M Kerckhoffs, Fred Brouns, Gerard Hornstra, Ronald P Mensink
    Abstract:

    Department of Human Biology and. Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands. d.kerckhoffs@hb.unimass.nl The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile. Publication Types: Review Review, Academic

Danielle A J M Kerckhoffs - One of the best experts on this subject based on the ideXlab platform.

  • effects on the human serum lipoprotein profile of β glucan soy protein and isoflavones plant sterols and stanols garlic and tocotrienols
    Journal of Nutrition, 2002
    Co-Authors: Danielle A J M Kerckhoffs, Fred Brouns, Gerard Hornstra, Ronald P Mensink
    Abstract:

    The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile.

  • effects on the human serum lipoprotein profile of β glucan soy protein and isoflavones plant sterols and stanols garlic and tocotrienols
    Journal of Nutrition, 2002
    Co-Authors: Danielle A J M Kerckhoffs, Fred Brouns, Gerard Hornstra, Ronald P Mensink
    Abstract:

    Department of Human Biology and. Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands. d.kerckhoffs@hb.unimass.nl The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile. Publication Types: Review Review, Academic

Farooq Ahmad Khan - One of the best experts on this subject based on the ideXlab platform.

  • dose dependent suppression of serum cholesterol by tocotrienol rich fraction trf25 of rice bran in hypercholesterolemic humans
    Atherosclerosis, 2002
    Co-Authors: Asaf A Qureshi, Saeed A Sami, Winston Salser, Farooq Ahmad Khan
    Abstract:

    Tocotrienols are effective in lowering serum total and LDL-cholesterol levels by inhibiting the hepatic enzymic activity of beta-hydroxy-beta-methylglutaryl coenzymeA (HMG-CoA) reductase through the post-transcriptional mechanism. alpha-Tocopherol, however, has an opposite effect (induces) on this enzyme activity. Since tocotrienols are also converted to tocopherols in vivo, it is necessary not to exceed a certain dose, as this would be counter-productive. The present study demonstrates the effects of various doses of a tocotrienol-rich fraction (TRF25) of stabilized and heated rice bran in hypercholesterolemic human subjects on serum lipid parameters. Ninety (18/group) hypercholesterolemic human subjects participated in this study, which comprised three phases of 35 days each. The subjects were initially placed on the American Heart Association (AHA) Step-1 diet and the effects noted. They were then administered 25, 50, 100, and 200 mg/day of TRF25 while on the restricted (AHA) diet. The results show that a dose of 100 mg/day of TRF25 produce maximum decreases of 20, 25, 14 (P<0.05) and 12%, respectively, in serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides compared with the baseline values, suggesting that a dose of 100 mg/day TRF25 plus AHA Step-1 diet may be the optimal dose for controlling the risk of coronary heart disease in hypercholesterolemic human subjects.

Gerard Hornstra - One of the best experts on this subject based on the ideXlab platform.

  • effects on the human serum lipoprotein profile of β glucan soy protein and isoflavones plant sterols and stanols garlic and tocotrienols
    Journal of Nutrition, 2002
    Co-Authors: Danielle A J M Kerckhoffs, Fred Brouns, Gerard Hornstra, Ronald P Mensink
    Abstract:

    The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile.

  • effects on the human serum lipoprotein profile of β glucan soy protein and isoflavones plant sterols and stanols garlic and tocotrienols
    Journal of Nutrition, 2002
    Co-Authors: Danielle A J M Kerckhoffs, Fred Brouns, Gerard Hornstra, Ronald P Mensink
    Abstract:

    Department of Human Biology and. Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands. d.kerckhoffs@hb.unimass.nl The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols, garlic and tocotrienols on serum lipoproteins have been of great interest the last decade. From a critical review of the literature, it appeared that recent studies found positive as well as no effects of beta-glucan from oats on serum LDL cholesterol concentrations. These conflicting results may suggest that the cholesterol-lowering activity of products rich in oat beta-glucan depends on factors, such as its viscosity in the gastrointestinal tract, the food matrix and/or food processing. The effects of beta-glucan from barley or yeast on the lipoprotein profile are promising, but more human trials are needed to further substantiate these effects. It is still not clear whether the claimed hypocholesterolemic effects of soy can be attributed solely to the isoflavones. Several studies found no changes in serum LDL cholesterol concentrations after consumption of isolated soy isoflavones (without soy protein), indicating that a combination of soy protein and isoflavones may be needed for eliciting a cholesterol-lowering effect of soy. Therefore, the exact (combination of) active ingredients in soy products need to be identified. The daily consumption of 2-3 g of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It has been demonstrated that functional foods enriched with plant sterols and stanols are effective in various population groups, and in combination with cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be used as a lipid-lowering agent is still uncertain. It is important to characterize the active components in garlic and their bioavailability after ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil have favorable effects on the human serum lipoprotein profile. Publication Types: Review Review, Academic