Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo

Detalhes bibliográficos
Autor(a) principal: Mostardeiro, Vitor Bastianello
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/23603
Resumo: Neuroinflammation is a process associated with various neurodegenerative diseases, especially Parkinson’s and Alzheimer’s Disease. In the Central Nervous System (CNS), microglial cells are the most important macrophages and their activation is closely related to the inflammatory process seen in neurodegenerative diseases. The purinergic sysem also has a very intimate relationship with the inflammatory process and its components might be modulating inflammatory responses in the CNS. Chlorogenic Acid (CGA) is a natural product known for its antioxidant and anti-inflammatory activities that would be able to modulate the responses of the purinergic system, interfering with the neuroinflammatory process. Thus, this study aimed to investigate the possible in vitro therapeutic effects of CGA in a model involving the purinergic system and microglial cells (BV-2) exposed to lipopolysaccharide (LPS) (1 ug/mL) and treatment with an increasing concentration effect curve of CGA (0.5 to 300 uM), for 24 and 96 hours. Results show that CGA is able to modulate purinergic activity by restoring ATP hydrolysis levels to those of the control, and increasing the Adenosine breakdown. CGA also acted on the expression of purinergic receptors P2X7 and A2A, and greatly reducing the releases of the pro-inflammatory cytokine IL-1β. It was also verified that this compound reduced the ratio of migrated cells after LPS challenge at both times. Therefore, despite the restrictions of in vitro protocols, this work highlights the therapeutic potential of this natural product in the possible treatment of inflammation in the CNS.
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spelling 2022-01-25T11:57:57Z2022-01-25T11:57:57Z2021-09-16http://repositorio.ufsm.br/handle/1/23603Neuroinflammation is a process associated with various neurodegenerative diseases, especially Parkinson’s and Alzheimer’s Disease. In the Central Nervous System (CNS), microglial cells are the most important macrophages and their activation is closely related to the inflammatory process seen in neurodegenerative diseases. The purinergic sysem also has a very intimate relationship with the inflammatory process and its components might be modulating inflammatory responses in the CNS. Chlorogenic Acid (CGA) is a natural product known for its antioxidant and anti-inflammatory activities that would be able to modulate the responses of the purinergic system, interfering with the neuroinflammatory process. Thus, this study aimed to investigate the possible in vitro therapeutic effects of CGA in a model involving the purinergic system and microglial cells (BV-2) exposed to lipopolysaccharide (LPS) (1 ug/mL) and treatment with an increasing concentration effect curve of CGA (0.5 to 300 uM), for 24 and 96 hours. Results show that CGA is able to modulate purinergic activity by restoring ATP hydrolysis levels to those of the control, and increasing the Adenosine breakdown. CGA also acted on the expression of purinergic receptors P2X7 and A2A, and greatly reducing the releases of the pro-inflammatory cytokine IL-1β. It was also verified that this compound reduced the ratio of migrated cells after LPS challenge at both times. Therefore, despite the restrictions of in vitro protocols, this work highlights the therapeutic potential of this natural product in the possible treatment of inflammation in the CNS.A neuroinflamação é um processo associado à várias doenças neurodegenerativas, especialmente as doenças de Parkinson e Alzheimer (DA). No caso do Sistema Nervoso Central, as células da micróglia são importantes macrófagos e a sua ativação está muito relacionada com os processos inflamatórios verificados em doenças neurodegenerativas. O sistema purinérgico também tem relação direta com o processo inflamatório e seus componentes podem estar modulando respostas inflamatórias em células do SNC. O Ácido Clorogênico (CGA) é um produto natural conhecido pela sua atividade antioxidante e anti-inflamatória que seria capaz de modular as respostas do sistema purinérgico, interferindo no processo neuroinflamatório. Dessa forma, buscou-se investigar os possíveis efeitos terapêuticos in vitro do ácido clorogênico em um modelo envolvendo o sistema purinérgico e linhagem celular de micróglia (BV-2) exposta ao lipopolissacarídeo (LPS) (1 ug/mL) e tratamento com uma curva de CGA (0,5 a 300 uM), por 24 e 96 horas. Os resultados demonstram que o CGA consegue modular a atividade de enzimas purinérgicas, restaurando os níveis de hidrólise de ATP aos do controle e aumentando a degradação de Adenosina. O CGA também atuou na expressão dos receptores purinérgicos P2X7 e A2A, também reduzindo muito a liberação da citocina pró inflamatória IL-1β. Também foi verificado que esse composto ameniza a migração microglial induzida por LPS em ambos os tempos. Sendo assim, apesar das restrições de protocolos in vitro, o presente trabalho evidenciou o potencial terapêutico desse produto natural no possível tratamento de inflamações no SNC.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESConselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade 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/openAccessDoença de AlzheimerCélulas microgliaisNeuroinflamaçãoNeurodegeneraçãoSistema purinérgicoAlzheimer’s diseaseMicroglial cellsNeuroinflammationNeurodegenerationPurinergic systemCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeoEffects of chlorogenic acid in modulation of purinergic signalling and inflammatory markers of LPS-exposed microglial cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMorsch, Vera Maria Melchiorshttp://lattes.cnpq.br/1519648219507868Baldissarelli, JucimaraSpanevello, Roselia Mariahttp://lattes.cnpq.br/8324737313856194Mostardeiro, Vitor Bastianello200800000002600600600600600b9bc6912-392b-4d80-ac50-8a56c12e490257b26653-e684-4339-913e-dc4aca8ddc1592291d22-7125-46e7-bdd1-5933edec5881da7d65ae-3939-4ddc-8509-095f11925052reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2021_MOSTARDEIRO_VITOR.pdfDIS_PPGCBBT_2021_MOSTARDEIRO_VITOR.pdfDissertaçãoapplication/pdf2840515http://repositorio.ufsm.br/bitstream/1/23603/1/DIS_PPGCBBT_2021_MOSTARDEIRO_VITOR.pdf9240c1c34a8f528a39a244a04c54f9ebMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
dc.title.alternative.eng.fl_str_mv Effects of chlorogenic acid in modulation of purinergic signalling and inflammatory markers of LPS-exposed microglial cells
title Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
spellingShingle Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
Mostardeiro, Vitor Bastianello
Doença de Alzheimer
Células microgliais
Neuroinflamação
Neurodegeneração
Sistema purinérgico
Alzheimer’s disease
Microglial cells
Neuroinflammation
Neurodegeneration
Purinergic system
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
title_full Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
title_fullStr Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
title_full_unstemmed Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
title_sort Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
author Mostardeiro, Vitor Bastianello
author_facet Mostardeiro, Vitor Bastianello
author_role author
dc.contributor.advisor1.fl_str_mv Morsch, Vera Maria Melchiors
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1519648219507868
dc.contributor.referee1.fl_str_mv Baldissarelli, Jucimara
dc.contributor.referee2.fl_str_mv Spanevello, Roselia Maria
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8324737313856194
dc.contributor.author.fl_str_mv Mostardeiro, Vitor Bastianello
contributor_str_mv Morsch, Vera Maria Melchiors
Baldissarelli, Jucimara
Spanevello, Roselia Maria
dc.subject.por.fl_str_mv Doença de Alzheimer
Células microgliais
Neuroinflamação
Neurodegeneração
Sistema purinérgico
topic Doença de Alzheimer
Células microgliais
Neuroinflamação
Neurodegeneração
Sistema purinérgico
Alzheimer’s disease
Microglial cells
Neuroinflammation
Neurodegeneration
Purinergic system
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv Alzheimer’s disease
Microglial cells
Neuroinflammation
Neurodegeneration
Purinergic system
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Neuroinflammation is a process associated with various neurodegenerative diseases, especially Parkinson’s and Alzheimer’s Disease. In the Central Nervous System (CNS), microglial cells are the most important macrophages and their activation is closely related to the inflammatory process seen in neurodegenerative diseases. The purinergic sysem also has a very intimate relationship with the inflammatory process and its components might be modulating inflammatory responses in the CNS. Chlorogenic Acid (CGA) is a natural product known for its antioxidant and anti-inflammatory activities that would be able to modulate the responses of the purinergic system, interfering with the neuroinflammatory process. Thus, this study aimed to investigate the possible in vitro therapeutic effects of CGA in a model involving the purinergic system and microglial cells (BV-2) exposed to lipopolysaccharide (LPS) (1 ug/mL) and treatment with an increasing concentration effect curve of CGA (0.5 to 300 uM), for 24 and 96 hours. Results show that CGA is able to modulate purinergic activity by restoring ATP hydrolysis levels to those of the control, and increasing the Adenosine breakdown. CGA also acted on the expression of purinergic receptors P2X7 and A2A, and greatly reducing the releases of the pro-inflammatory cytokine IL-1β. It was also verified that this compound reduced the ratio of migrated cells after LPS challenge at both times. Therefore, despite the restrictions of in vitro protocols, this work highlights the therapeutic potential of this natural product in the possible treatment of inflammation in the CNS.
publishDate 2021
dc.date.issued.fl_str_mv 2021-09-16
dc.date.accessioned.fl_str_mv 2022-01-25T11:57:57Z
dc.date.available.fl_str_mv 2022-01-25T11:57:57Z
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dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
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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
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