Efeitos do ácido clorogênico na modulação da sinalização purinérgica e perfil inflamatório em células microgliais expostas ao lipopolissacarídeo
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do 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. |
id |
UFSM_5032591fc770cc0bb4449315f577e2d9 |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/23603 |
network_acronym_str |
UFSM |
network_name_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
repository_id_str |
|
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:Biblioteca Digital de Teses e Dissertações do 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; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/23603/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/23603/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD531/236032022-07-26 12:29:19.368oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-07-26T15:29:19Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
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 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/23603 |
url |
http://repositorio.ufsm.br/handle/1/23603 |
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 |
dc.relation.authority.fl_str_mv |
b9bc6912-392b-4d80-ac50-8a56c12e4902 57b26653-e684-4339-913e-dc4aca8ddc15 92291d22-7125-46e7-bdd1-5933edec5881 da7d65ae-3939-4ddc-8509-095f11925052 |
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 |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/23603/1/DIS_PPGCBBT_2021_MOSTARDEIRO_VITOR.pdf http://repositorio.ufsm.br/bitstream/1/23603/2/license_rdf http://repositorio.ufsm.br/bitstream/1/23603/3/license.txt |
bitstream.checksum.fl_str_mv |
9240c1c34a8f528a39a244a04c54f9eb 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1801485180440936448 |