Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.

Detalhes bibliográficos
Autor(a) principal: Gadelha, Francisco Allysson Assis Ferreira
Data de Publicação: 2024
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/31388
Resumo: Acute lung injury (ALI) is an inflammatory disease with high mortality that affects patients in intensive care and has become a global health problem during the COVID-19 pandemic. Musa paradisiaca L. (banana) is a cosmopolitan plant, and its inflorescence is used in many countries to treat inflammation, however, in Brazil, it is discarded in most cultures. The objective of this study was to evaluate the anti-inflammatory and immunomodulatory activities of the inflorescence extract and its fractions through in vitro and in vivo tests, in the experimental model of ALI induced with lipopolysaccharide (LPS). Optical and immunofluorescence microscopy, flow cytometry, immunoenzymatic and colorimetric assays (ELISA) and histology were used to evaluate anti-inflammatory parameters. The hydroalcoholic extract of Musa (HEM) (100 μg/mL) and its fractions ethyl acetate (FA), n-butanol (FNB), hexane (FH) and dichloromethane (FD) (25 and 50 μg/mL) did not present toxicity in peritoneal macrophages. In in vitro screening, HEM and FA and FH decreased NO production and expression of TLR4 and CD18 receptors. In addition, HEM increased IL-10 production. In in vivo experiments, HEM and FH were evaluated. In animals with ALI treated with HEM, a decrease in migration was observed, mainly of neutrophils in the BALF, in the alveolar region and in the blood, correlating with the decrease in CD18 expression, however, FH (100 mg/kg) did not decrease the migration of cells to the lung cavity as well as edema, cellular infiltration and hemorrhage in the tissue. Treatment with HEM reduced the protein content in BALF, edema, activation of NF-κB dependent on the TLR4 signaling pathway and decreased the production of IL-1β and TNF-α, reduced the amount of free DNA and myeloperoxidase activity (MPO). Corroborating the in vitro findings, treatment with HEM favored the production of IL-10 in BALF. Therefore, the M. paradisiaca inflorescence extract demonstrated anti-inflammatory and immunomodulatory activities in macrophages via decreased NO, increased IL-10 and, in mice with ALI, decreased lung inflammation via TLR4-NF-κB, reduced production of cytokines, as well as the decrease in CD18 expression, release of free DNA and MPO activity. Thus, this study presents scientific data that support the use of banana inflorescences in folk medicine and suggests the development of a pharmaceutical formulation to assist in the treatment of lung inflammation.
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spelling Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.FarmacologiaBananaNeutrófilosAtividade imunomoduladoraVia TLR4/NF-kBPharmacologyNeutrophilsImmunomodulatory activityTLR4/NF-κB pathwayCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAAcute lung injury (ALI) is an inflammatory disease with high mortality that affects patients in intensive care and has become a global health problem during the COVID-19 pandemic. Musa paradisiaca L. (banana) is a cosmopolitan plant, and its inflorescence is used in many countries to treat inflammation, however, in Brazil, it is discarded in most cultures. The objective of this study was to evaluate the anti-inflammatory and immunomodulatory activities of the inflorescence extract and its fractions through in vitro and in vivo tests, in the experimental model of ALI induced with lipopolysaccharide (LPS). Optical and immunofluorescence microscopy, flow cytometry, immunoenzymatic and colorimetric assays (ELISA) and histology were used to evaluate anti-inflammatory parameters. The hydroalcoholic extract of Musa (HEM) (100 μg/mL) and its fractions ethyl acetate (FA), n-butanol (FNB), hexane (FH) and dichloromethane (FD) (25 and 50 μg/mL) did not present toxicity in peritoneal macrophages. In in vitro screening, HEM and FA and FH decreased NO production and expression of TLR4 and CD18 receptors. In addition, HEM increased IL-10 production. In in vivo experiments, HEM and FH were evaluated. In animals with ALI treated with HEM, a decrease in migration was observed, mainly of neutrophils in the BALF, in the alveolar region and in the blood, correlating with the decrease in CD18 expression, however, FH (100 mg/kg) did not decrease the migration of cells to the lung cavity as well as edema, cellular infiltration and hemorrhage in the tissue. Treatment with HEM reduced the protein content in BALF, edema, activation of NF-κB dependent on the TLR4 signaling pathway and decreased the production of IL-1β and TNF-α, reduced the amount of free DNA and myeloperoxidase activity (MPO). Corroborating the in vitro findings, treatment with HEM favored the production of IL-10 in BALF. Therefore, the M. paradisiaca inflorescence extract demonstrated anti-inflammatory and immunomodulatory activities in macrophages via decreased NO, increased IL-10 and, in mice with ALI, decreased lung inflammation via TLR4-NF-κB, reduced production of cytokines, as well as the decrease in CD18 expression, release of free DNA and MPO activity. Thus, this study presents scientific data that support the use of banana inflorescences in folk medicine and suggests the development of a pharmaceutical formulation to assist in the treatment of lung inflammation.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA lesão pulmonar aguda (LPA) é uma doença inflamatória com alta mortalidade que afeta pacientes em terapia intensiva e se tornou um problema de saúde mundial durante a pandemia de COVID-19. A Musa paradisiaca L. (bananeira) é uma planta cosmopolita, e sua inflorescência é usada, em muitos países, no tratamento de inflamações, no entanto, no Brasil, é descartada na maioria das culturas. O objetivo deste estudo foi avaliar as atividades anti-inflamatória e imunomoduladora do extrato da inflorescência e de suas frações por meio de testes in vitro e in vivo, no modelo experimental de LPA induzido com lipopolissacarídeo (LPS). Microscopias óptica e de imunofluorescência, citometria de fluxo, ensaios imunoenzimáticos, colorimétricos (ELISA) e histologia foram utilizados para as avaliações dos parâmetros anti-inflamatórios. O extrato hidroalcoólico de Musa (HEM) (100 μg/mL) e suas frações acetato de etila (FA), n-butanólica (FNB), hexânica (FH) e diclorometano (FD) (25 e 50 μg/mL) não apresentaram toxicidade em macrófagos peritoneais. Na triagem in vitro, o HEM e as FA e FH diminuíram a produção de NO e expressão dos receptores TLR4 e CD18. Em adição, o HEM aumentou a produção de IL-10. Nos experimentos in vivo foram avaliados o HEM e a FH. Nos animais com LPA tratados com o HEM, observou-se diminuição na migração, principalmente, de neutrófilos no BALF, na região alveolar e no sangue correlacionando com a diminuição na expressão do CD18, entretanto, a FH (100 mg/kg) não diminuiu a migração de células para a cavidade pulmonar bem como edema, infiltrado celular e hemorragia no tecido. O tratamento com HEM reduziu o conteúdo proteico no BALF, o edema, a ativação do NF-κB dependente da via de sinalização TLR4 e diminuiu da produção de IL-1β e TNF-α, reduziu a quantidade de DNA livre e da atividade da mieloperoxidase (MPO). Corroborando com os achados in vitro, o tratamento com HEM favoreceu a produção de IL-10 no BALF. Portanto, o extrato da inflorescência de M. paradisiaca demonstrou atividades anti-inflamatória e imunomoduladora em macrófagos, via diminuição de NO, aumento de IL-10 e, em camundongos com LPA, pela diminuição da inflamação pulmonar via TLR4-NF-κB, redução da produção de citocinas, bem como pela diminuição da expressão de CD18, liberação de DNA livre e da atividade de MPO. Assim, este estudo apresenta dados científicos que apoiam o uso da inflorescência de bananeira na medicina popular e sugerindo-se o desenvolvimento de uma formulação farmacêutica para auxiliar no tratamento da inflamação pulmonar.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBPiuvezam, Marcia Reginahttp://lattes.cnpq.br/0961955935523938Dejani, Naiara Naianahttp://lattes.cnpq.br/3622954974849790Gadelha, Francisco Allysson Assis Ferreira2024-08-13T16:38:06Z2024-02-152024-08-13T16:38:06Z2024-02-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/31388porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2024-08-14T06:06:48Zoai:repositorio.ufpb.br:123456789/31388Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2024-08-14T06:06:48Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
title Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
spellingShingle Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
Gadelha, Francisco Allysson Assis Ferreira
Farmacologia
Banana
Neutrófilos
Atividade imunomoduladora
Via TLR4/NF-kB
Pharmacology
Neutrophils
Immunomodulatory activity
TLR4/NF-κB pathway
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
title_full Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
title_fullStr Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
title_full_unstemmed Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
title_sort Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
author Gadelha, Francisco Allysson Assis Ferreira
author_facet Gadelha, Francisco Allysson Assis Ferreira
author_role author
dc.contributor.none.fl_str_mv Piuvezam, Marcia Regina
http://lattes.cnpq.br/0961955935523938
Dejani, Naiara Naiana
http://lattes.cnpq.br/3622954974849790
dc.contributor.author.fl_str_mv Gadelha, Francisco Allysson Assis Ferreira
dc.subject.por.fl_str_mv Farmacologia
Banana
Neutrófilos
Atividade imunomoduladora
Via TLR4/NF-kB
Pharmacology
Neutrophils
Immunomodulatory activity
TLR4/NF-κB pathway
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Farmacologia
Banana
Neutrófilos
Atividade imunomoduladora
Via TLR4/NF-kB
Pharmacology
Neutrophils
Immunomodulatory activity
TLR4/NF-κB pathway
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Acute lung injury (ALI) is an inflammatory disease with high mortality that affects patients in intensive care and has become a global health problem during the COVID-19 pandemic. Musa paradisiaca L. (banana) is a cosmopolitan plant, and its inflorescence is used in many countries to treat inflammation, however, in Brazil, it is discarded in most cultures. The objective of this study was to evaluate the anti-inflammatory and immunomodulatory activities of the inflorescence extract and its fractions through in vitro and in vivo tests, in the experimental model of ALI induced with lipopolysaccharide (LPS). Optical and immunofluorescence microscopy, flow cytometry, immunoenzymatic and colorimetric assays (ELISA) and histology were used to evaluate anti-inflammatory parameters. The hydroalcoholic extract of Musa (HEM) (100 μg/mL) and its fractions ethyl acetate (FA), n-butanol (FNB), hexane (FH) and dichloromethane (FD) (25 and 50 μg/mL) did not present toxicity in peritoneal macrophages. In in vitro screening, HEM and FA and FH decreased NO production and expression of TLR4 and CD18 receptors. In addition, HEM increased IL-10 production. In in vivo experiments, HEM and FH were evaluated. In animals with ALI treated with HEM, a decrease in migration was observed, mainly of neutrophils in the BALF, in the alveolar region and in the blood, correlating with the decrease in CD18 expression, however, FH (100 mg/kg) did not decrease the migration of cells to the lung cavity as well as edema, cellular infiltration and hemorrhage in the tissue. Treatment with HEM reduced the protein content in BALF, edema, activation of NF-κB dependent on the TLR4 signaling pathway and decreased the production of IL-1β and TNF-α, reduced the amount of free DNA and myeloperoxidase activity (MPO). Corroborating the in vitro findings, treatment with HEM favored the production of IL-10 in BALF. Therefore, the M. paradisiaca inflorescence extract demonstrated anti-inflammatory and immunomodulatory activities in macrophages via decreased NO, increased IL-10 and, in mice with ALI, decreased lung inflammation via TLR4-NF-κB, reduced production of cytokines, as well as the decrease in CD18 expression, release of free DNA and MPO activity. Thus, this study presents scientific data that support the use of banana inflorescences in folk medicine and suggests the development of a pharmaceutical formulation to assist in the treatment of lung inflammation.
publishDate 2024
dc.date.none.fl_str_mv 2024-08-13T16:38:06Z
2024-02-15
2024-08-13T16:38:06Z
2024-02-05
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 https://repositorio.ufpb.br/jspui/handle/123456789/31388
url https://repositorio.ufpb.br/jspui/handle/123456789/31388
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
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