Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/22054 |
Resumo: | Ilex paraguariensis is a plant widely consumed in South America, used to prepare a tea-like beverage, called mate, rich in caffeine and polyphenols, with multiple biological activities including antioxidant, anti-obesity and neuroprotective proprieties. Nevertheless, studies about the Ilex paraguariensis biological properties are restricted, and its effects over the central nervous system are not well elucidated. Caffeine is a thermogenic agent that acts through the adenosine receptor, and its consumption is associated with a lower risk of age-associated neuropathologies. Alzheimer's disease is a progressive neurodegenerative disorder characterized by the presence of amyloid plaques in the brain formed by the deposition of insoluble β-amyloid peptides. Since several plants that have antioxidant proprieties are known to be neuroprotective, and also caffeine have thermogenic and neuroprotective proprieties, and oxidative stress correlates with Aβ-toxicity, the present study aims to investigate the effects of chronic treatment with Ilex paraguariensis extract in vivo on lipid metabolism and Aβ-induced toxicity model, and compare the effects of this last one with caffeine using Caenorhabditis elegans. Ilex paraguariensis-dependent modulation of fat metabolism in C. elegans was first investigated. Overall, Ilex paraguariensis decreased fat storage and increased body energy expenditure of worms. These effects depend on the purinergic system (ADOR-1) and nuclear hormone receptor (NHR-49), a key regulator gene of fat oxidation. Ilex paraguariensis also upregulated the expression of adipocyte triglyceride lipase 1 (ATGL-1), to modulate fat metabolism. After, the neuroprotective effects of Ilex paraguariensis and caffeine were analyzed. Ilex paraguariensis and caffeine increased the C. elegans lifespan and appeared to act directly as a reactive oxygen species scavenger, also delayed Aβ-induced paralysis and decreased AChE activity in C. elegans. The protective effect of Ilex paraguariensis against Aβ-induced paralysis was found to be dependent on heat shock factor (HSF-1) and FOXO-family transcription factor (DAF-16), which are respectively involved in aging-related processes and chaperone synthesis – responsible for the protein homeostasis; while that of caffeine was dependent only on DAF-16. The results were overall better when C. elegans was treated with Ilex paraguariensis than with caffeine. Due to a large number of constituents in the Ilex paraguariensis extract, it is difficult to identify the precise compound responsible for the beneficial effects. Synergistic interactions are important in phytomedicines, therefore the effects of Ilex paraguariensis extract can be less when a single compound is isolated and used at low concentrations, as in the case of caffeine. |
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2021-08-24T21:13:02Z2021-08-24T21:13:02Z2020-03-25http://repositorio.ufsm.br/handle/1/22054Ilex paraguariensis is a plant widely consumed in South America, used to prepare a tea-like beverage, called mate, rich in caffeine and polyphenols, with multiple biological activities including antioxidant, anti-obesity and neuroprotective proprieties. Nevertheless, studies about the Ilex paraguariensis biological properties are restricted, and its effects over the central nervous system are not well elucidated. Caffeine is a thermogenic agent that acts through the adenosine receptor, and its consumption is associated with a lower risk of age-associated neuropathologies. Alzheimer's disease is a progressive neurodegenerative disorder characterized by the presence of amyloid plaques in the brain formed by the deposition of insoluble β-amyloid peptides. Since several plants that have antioxidant proprieties are known to be neuroprotective, and also caffeine have thermogenic and neuroprotective proprieties, and oxidative stress correlates with Aβ-toxicity, the present study aims to investigate the effects of chronic treatment with Ilex paraguariensis extract in vivo on lipid metabolism and Aβ-induced toxicity model, and compare the effects of this last one with caffeine using Caenorhabditis elegans. Ilex paraguariensis-dependent modulation of fat metabolism in C. elegans was first investigated. Overall, Ilex paraguariensis decreased fat storage and increased body energy expenditure of worms. These effects depend on the purinergic system (ADOR-1) and nuclear hormone receptor (NHR-49), a key regulator gene of fat oxidation. Ilex paraguariensis also upregulated the expression of adipocyte triglyceride lipase 1 (ATGL-1), to modulate fat metabolism. After, the neuroprotective effects of Ilex paraguariensis and caffeine were analyzed. Ilex paraguariensis and caffeine increased the C. elegans lifespan and appeared to act directly as a reactive oxygen species scavenger, also delayed Aβ-induced paralysis and decreased AChE activity in C. elegans. The protective effect of Ilex paraguariensis against Aβ-induced paralysis was found to be dependent on heat shock factor (HSF-1) and FOXO-family transcription factor (DAF-16), which are respectively involved in aging-related processes and chaperone synthesis – responsible for the protein homeostasis; while that of caffeine was dependent only on DAF-16. The results were overall better when C. elegans was treated with Ilex paraguariensis than with caffeine. Due to a large number of constituents in the Ilex paraguariensis extract, it is difficult to identify the precise compound responsible for the beneficial effects. Synergistic interactions are important in phytomedicines, therefore the effects of Ilex paraguariensis extract can be less when a single compound is isolated and used at low concentrations, as in the case of caffeine.A Ilex paraguariensis é uma planta amplamente consumida na América do Sul, usada para preparar uma bebida semelhante ao chá, conhecida como mate, rica em cafeína e polifenóis, com múltiplas atividades biológicas, incluindo propriedades antioxidantes, antiobesidade e neuroprotetora. No entanto, estudos sobre as propriedades biológicas de Ilex paraguariensis são restritos e seus efeitos sobre o sistema nervoso central não são bem elucidados. A cafeína é um agente termogênico que atua através do receptor de adenosina e seu consumo está relacionado a um menor risco de neuropatologias associadas à idade. A doença de Alzheimer é uma doença neurodegenerativa progressiva caracterizada pela presença de placas amiloides no cérebro formada pela deposição de peptídeos β-amiloides insolúveis. Como várias plantas que possuem propriedades antioxidantes são conhecidas por serem neuroprotetoras, e também a cafeína possui propriedades termogênica e neuroprotetora, e o estresse oxidativo se correlaciona com a toxicidade do peptídeo β-amilóide, o presente estudo tem como objetivo investigar os efeitos do tratamento crônico com extrato de Ilex paraguariensis in vivo no metabolismo lipídico e no modelo de toxicidade induzida por βA, e comparar os efeitos deste último com a cafeína usando Caenorhabditis elegans. A modulação do metabolismo da gordura dependente de Ilex paraguariensis em C. elegans foi investigada pela primeira vez. No geral, Ilex paraguariensis diminuiu o armazenamento de lipídeos e aumentou o gasto de energia corporal nos animais. Esses efeitos dependem do sistema purinérgico (ADOR-1) e do receptor nuclear hormonal (NHR-49), um regulador chave da oxidação da gordura. Ilex paraguariensis também aumentou positivamente a expressão da lipase de triglicerídeos dos adipócitos tipo 1 (ATGL-1), para modular o metabolismo da gordura. Após, foram analisados os efeitos neuroprotetores de Ilex paraguariensis e cafeína. Ilex paraguariensis e cafeína aumentaram a sobrevivência de C. elegans e parecem atuar diretamente como sequestrador de espécies reativas de oxigênio, também atrasaram a paralisia induzida pelo peptídeo βA e diminuíram a atividade da enzima AChE em C. elegans. Verificou-se que o efeito protetor de Ilex paraguariensis contra a paralisia induzida pelo peptídeo βA foi depende do fator de choque térmico (HSF-1) e do fator de transcrição da família FOXO (DAF-16), que estão envolvidos respectivamente nos processos relacionados ao envelhecimento e na síntese de chaperonas – responsável pela homeostase proteica; enquanto o da cafeína dependia apenas da DAF-16. Os resultados foram melhores quando C. elegans foi tratado com Ilex paraguariensis do que com cafeína. Devido ao grande número de constituintes no extrato de Ilex paraguariensis, é difícil identificar o composto responsável pelos efeitos benéficos. Interações sinérgicas são importantes em fitomedicamentos, portanto os efeitos do extrato de Ilex paraguariensis podem ser menores quando um único composto é isolado e usado em baixas concentrações, como no caso da cafeína.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessProdutos naturaisErva mateMetabolismo de lipídiosConsumo de oxigênioDoenças neurodegenerativasDoença de AlzheimerBeta amilóideNatural productsYerba mateFat metabolismOxygen consumptionNeurodegenerative diseasesAlzheimer's diseaseAmyloid betaCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAvaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSoares, Félix Alexandre Antuneshttp://lattes.cnpq.br/8752453650114092Boeck, Carina RodriguesCharão, Mariele FeifferBarbosa, Nilda Berenice de VargasEmanuelli, Tatianahttp://lattes.cnpq.br/0382013676927848Machado, Marina Lopes2008000000026006006006006006006003aef53b7-b173-4c56-a944-bed2de5e5dda121a3386-f146-43dc-9b04-c78a9b47d7d4c5e16dd4-ecf7-401b-8735-9c3c3a6cc8fa0ee68c8e-662e-4cd4-8ad3-e575e1f38f160198eecb-263d-4159-82c5-3698b0253f4f22aa7bd2-5905-49f4-b5ac-e7167850124freponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2020_MACHADO_MARINA.pdfTES_PPGCBBT_2020_MACHADO_MARINA.pdfTeseapplication/pdf9848887http://repositorio.ufsm.br/bitstream/1/22054/1/TES_PPGCBBT_2020_MACHADO_MARINA.pdfab0f7900bf2eb8e1fe832767f780cc9bMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
title |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
spellingShingle |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans Machado, Marina Lopes Produtos naturais Erva mate Metabolismo de lipídios Consumo de oxigênio Doenças neurodegenerativas Doença de Alzheimer Beta amilóide Natural products Yerba mate Fat metabolism Oxygen consumption Neurodegenerative diseases Alzheimer's disease Amyloid beta CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
title_full |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
title_fullStr |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
title_full_unstemmed |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
title_sort |
Avaliação do efeito do extrato aquoso de Ilex paraguariensis e cafeína sobre o metabolismo e a doença de Alzheimer em Caenorhabditis elegans |
author |
Machado, Marina Lopes |
author_facet |
Machado, Marina Lopes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8752453650114092 |
dc.contributor.referee1.fl_str_mv |
Boeck, Carina Rodrigues |
dc.contributor.referee2.fl_str_mv |
Charão, Mariele Feiffer |
dc.contributor.referee3.fl_str_mv |
Barbosa, Nilda Berenice de Vargas |
dc.contributor.referee4.fl_str_mv |
Emanuelli, Tatiana |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0382013676927848 |
dc.contributor.author.fl_str_mv |
Machado, Marina Lopes |
contributor_str_mv |
Soares, Félix Alexandre Antunes Boeck, Carina Rodrigues Charão, Mariele Feiffer Barbosa, Nilda Berenice de Vargas Emanuelli, Tatiana |
dc.subject.por.fl_str_mv |
Produtos naturais Erva mate Metabolismo de lipídios Consumo de oxigênio Doenças neurodegenerativas Doença de Alzheimer Beta amilóide |
topic |
Produtos naturais Erva mate Metabolismo de lipídios Consumo de oxigênio Doenças neurodegenerativas Doença de Alzheimer Beta amilóide Natural products Yerba mate Fat metabolism Oxygen consumption Neurodegenerative diseases Alzheimer's disease Amyloid beta CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Natural products Yerba mate Fat metabolism Oxygen consumption Neurodegenerative diseases Alzheimer's disease Amyloid beta |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Ilex paraguariensis is a plant widely consumed in South America, used to prepare a tea-like beverage, called mate, rich in caffeine and polyphenols, with multiple biological activities including antioxidant, anti-obesity and neuroprotective proprieties. Nevertheless, studies about the Ilex paraguariensis biological properties are restricted, and its effects over the central nervous system are not well elucidated. Caffeine is a thermogenic agent that acts through the adenosine receptor, and its consumption is associated with a lower risk of age-associated neuropathologies. Alzheimer's disease is a progressive neurodegenerative disorder characterized by the presence of amyloid plaques in the brain formed by the deposition of insoluble β-amyloid peptides. Since several plants that have antioxidant proprieties are known to be neuroprotective, and also caffeine have thermogenic and neuroprotective proprieties, and oxidative stress correlates with Aβ-toxicity, the present study aims to investigate the effects of chronic treatment with Ilex paraguariensis extract in vivo on lipid metabolism and Aβ-induced toxicity model, and compare the effects of this last one with caffeine using Caenorhabditis elegans. Ilex paraguariensis-dependent modulation of fat metabolism in C. elegans was first investigated. Overall, Ilex paraguariensis decreased fat storage and increased body energy expenditure of worms. These effects depend on the purinergic system (ADOR-1) and nuclear hormone receptor (NHR-49), a key regulator gene of fat oxidation. Ilex paraguariensis also upregulated the expression of adipocyte triglyceride lipase 1 (ATGL-1), to modulate fat metabolism. After, the neuroprotective effects of Ilex paraguariensis and caffeine were analyzed. Ilex paraguariensis and caffeine increased the C. elegans lifespan and appeared to act directly as a reactive oxygen species scavenger, also delayed Aβ-induced paralysis and decreased AChE activity in C. elegans. The protective effect of Ilex paraguariensis against Aβ-induced paralysis was found to be dependent on heat shock factor (HSF-1) and FOXO-family transcription factor (DAF-16), which are respectively involved in aging-related processes and chaperone synthesis – responsible for the protein homeostasis; while that of caffeine was dependent only on DAF-16. The results were overall better when C. elegans was treated with Ilex paraguariensis than with caffeine. Due to a large number of constituents in the Ilex paraguariensis extract, it is difficult to identify the precise compound responsible for the beneficial effects. Synergistic interactions are important in phytomedicines, therefore the effects of Ilex paraguariensis extract can be less when a single compound is isolated and used at low concentrations, as in the case of caffeine. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-03-25 |
dc.date.accessioned.fl_str_mv |
2021-08-24T21:13:02Z |
dc.date.available.fl_str_mv |
2021-08-24T21:13:02Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/22054 |
url |
http://repositorio.ufsm.br/handle/1/22054 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
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atendimento.sib@ufsm.br||tedebc@gmail.com |
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1801485180379070464 |