Avaliação in vitro e in vivo da atividade imunomoduladora do extrato e frações da inflorescência de Musa paradisiaca L.
Autor(a) principal: | |
---|---|
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. |
id |
UFPB_b374e7588592b9ce1610d428b30d7656 |
---|---|
oai_identifier_str |
oai:repositorio.ufpb.br:123456789/31388 |
network_acronym_str |
UFPB |
network_name_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository_id_str |
|
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 |
_version_ |
1815449726355505152 |