Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/230935 |
Resumo: | Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions. |
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Dourado, Naiara SilvaSouza, Cleide Santos deCarneiro, Monique Marylin Alves de AlmeidaSilva, Alessandra Bispo daSantos, Balbino Lino dosSilva, Victor Diogenes Amaral daAssis, Adriano Martimbianco deSilva, Jussemara Souza daSouza, Diogo Onofre Gomes deCosta, Maria de Fátima DiasButt, Arthur MorganCosta, Silvia Lima2021-10-20T04:22:32Z20201663-4365http://hdl.handle.net/10183/230935001132036Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions.application/pdfengFrontiers in aging neuroscience. Lausanne. Vol. 12 (May 2020), 119, 14 p.NeuroimunomodulaçãoMicrogliaNeuroproteçãoApigeninaDoença de AlzheimerNeuroinflammationNeuroprotectionAnti-inflammatoryMicrogliaFlavonoidsNeuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's diseaseEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001132036.pdf.txt001132036.pdf.txtExtracted Texttext/plain75002http://www.lume.ufrgs.br/bitstream/10183/230935/2/001132036.pdf.txt2575648f898a7ab5ab4d0bc44510f56fMD52ORIGINAL001132036.pdfTexto completo (inglês)application/pdf6175851http://www.lume.ufrgs.br/bitstream/10183/230935/1/001132036.pdfca52d9b54e4ebb56b7c1dc2c6a85bee0MD5110183/2309352021-11-20 05:50:08.805927oai:www.lume.ufrgs.br:10183/230935Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-11-20T07:50:08Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
title |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
spellingShingle |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease Dourado, Naiara Silva Neuroimunomodulação Microglia Neuroproteção Apigenina Doença de Alzheimer Neuroinflammation Neuroprotection Anti-inflammatory Microglia Flavonoids |
title_short |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
title_full |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
title_fullStr |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
title_full_unstemmed |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
title_sort |
Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease |
author |
Dourado, Naiara Silva |
author_facet |
Dourado, Naiara Silva Souza, Cleide Santos de Carneiro, Monique Marylin Alves de Almeida Silva, Alessandra Bispo da Santos, Balbino Lino dos Silva, Victor Diogenes Amaral da Assis, Adriano Martimbianco de Silva, Jussemara Souza da Souza, Diogo Onofre Gomes de Costa, Maria de Fátima Dias Butt, Arthur Morgan Costa, Silvia Lima |
author_role |
author |
author2 |
Souza, Cleide Santos de Carneiro, Monique Marylin Alves de Almeida Silva, Alessandra Bispo da Santos, Balbino Lino dos Silva, Victor Diogenes Amaral da Assis, Adriano Martimbianco de Silva, Jussemara Souza da Souza, Diogo Onofre Gomes de Costa, Maria de Fátima Dias Butt, Arthur Morgan Costa, Silvia Lima |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Dourado, Naiara Silva Souza, Cleide Santos de Carneiro, Monique Marylin Alves de Almeida Silva, Alessandra Bispo da Santos, Balbino Lino dos Silva, Victor Diogenes Amaral da Assis, Adriano Martimbianco de Silva, Jussemara Souza da Souza, Diogo Onofre Gomes de Costa, Maria de Fátima Dias Butt, Arthur Morgan Costa, Silvia Lima |
dc.subject.por.fl_str_mv |
Neuroimunomodulação Microglia Neuroproteção Apigenina Doença de Alzheimer |
topic |
Neuroimunomodulação Microglia Neuroproteção Apigenina Doença de Alzheimer Neuroinflammation Neuroprotection Anti-inflammatory Microglia Flavonoids |
dc.subject.eng.fl_str_mv |
Neuroinflammation Neuroprotection Anti-inflammatory Microglia Flavonoids |
description |
Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2021-10-20T04:22:32Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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eng |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in aging neuroscience. Lausanne. Vol. 12 (May 2020), 119, 14 p. |
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openAccess |
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