A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos

Detalhes bibliográficos
Autor(a) principal: SANTIAGO, Luis Ângelo Macedo
Data de Publicação: 2023
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
Texto Completo: https://tedebc.ufma.br/jspui/handle/tede/tede/5280
Resumo: Osteoarthritis (OA) is a pathology characterized by the progressive erosion of articular cartilage, with concomitant structural and functional changes in the tissues around the joints. In this context, medicinal plants have become relevant tools in terms of their potential role in the prevention and treatment of OA, providing a safe and effective therapeutic or adjuvant approach. The aim of this study was to investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of monosodium iodoacetate (MIA)-induced OA in rats. From the plant material, we obtained the crude extract by maceration with 70% hydroalcoholic solvent (BoHE), followed by fractionation with solvents in order of increasing polarity, obtaining the ethyl acetate (BoEA) fraction. The compound ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-PDA) and analytical curve. MIA-induced OA was performed on the right knee with a maximum volume of 2 mg/25 μL at the tibiopatellar femur joint, through the patellar ligament. All animals were previously sedated with ketamine hydrochloride® 10% (90 mg/kg) and then anesthetized using xylazine hydrochloride® 2% (5 mg/kg) in the intraperitoneal region. The doses of BoEA and ElAc compounds, as well as Indomethacin and sorbitol were performed via 12/12 hour gavage. Gavages were performed by administering a volume of 1 mL and adjusted according to the animal's weighing performed before the procedure. We evaluate the animals through clinical and radiological tests every 7 days. On the 29th day, euthanasia was performed by deep intraperitoneal anesthesia at a dosage of 0.3 ml of Xylazine (80mL/kg) + 0.3 ml of Ketamine (10mg/kg). All biological material was removed by puncture of the aorta, totaling 08-10 mL of blood in tubes containing EDTA. The results demonstrated that doses of the compounds BoEA and ElAc administered in the long term were capable of inducing anti- inflammatory and antinociceptive action evidenced through clinical tests and proved to be decisive in this process, inhibition evidenced by the decrease in serum levels of TNF-α and increase in IL -10 detected after 28 days of treatment. In relation to the radiological and histopathological images of the present study, we observed in the untreated group the presence of exuberant marginal osteophytes, subchondral bone sclerosis, areas of cartilage erosion and medial patellar dislocation, a case very different from the animals that were treated with phytochemical compounds, where they showed reduced progression of joint damage evidenced with lower degrees of joint changes. We concluded that the effects of BoEA and ElAc were able to reduce pain, inhibit the activity of catabolic pathways and consequently, inflammation through regulation and reciprocal balance of anti-inflammatory and pro-inflammatory cytokines in MIA-induced OA, in addition to attenuating the cartilage degeneration evidenced by radiological and histological images.
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spelling SOUSA, Eduardo Martins dehttp://lattes.cnpq.br/4448263553675550SOUSA, Eduardo Martinshttp://lattes.cnpq.br/4448263553675550PESSOA, Débora Luana Ribeirohttp://lattes.cnpq.br/2537676284852975COSTA, Adeliane Castro dahttp://lattes.cnpq.br/9373163292240939COELHO, Marsen Garcia Pintohttp://lattes.cnpq.br/4468352500732645MACIEL, Márcia Cristina Gonçalveshttp://lattes.cnpq.br/0645092224285117http://lattes.cnpq.br/4779581184278191SANTIAGO, Luis Ângelo Macedo2024-05-13T12:39:26Z2023-10-31SANTIAGO, Luis Ângelo Macedo. A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos. 2023. 79 f. Tese (Programa de Pós-Graduação em Rede - Rede de Biodiversidade e Biotecnologia da Amazônia Legal/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.https://tedebc.ufma.br/jspui/handle/tede/tede/5280Osteoarthritis (OA) is a pathology characterized by the progressive erosion of articular cartilage, with concomitant structural and functional changes in the tissues around the joints. In this context, medicinal plants have become relevant tools in terms of their potential role in the prevention and treatment of OA, providing a safe and effective therapeutic or adjuvant approach. The aim of this study was to investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of monosodium iodoacetate (MIA)-induced OA in rats. From the plant material, we obtained the crude extract by maceration with 70% hydroalcoholic solvent (BoHE), followed by fractionation with solvents in order of increasing polarity, obtaining the ethyl acetate (BoEA) fraction. The compound ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-PDA) and analytical curve. MIA-induced OA was performed on the right knee with a maximum volume of 2 mg/25 μL at the tibiopatellar femur joint, through the patellar ligament. All animals were previously sedated with ketamine hydrochloride® 10% (90 mg/kg) and then anesthetized using xylazine hydrochloride® 2% (5 mg/kg) in the intraperitoneal region. The doses of BoEA and ElAc compounds, as well as Indomethacin and sorbitol were performed via 12/12 hour gavage. Gavages were performed by administering a volume of 1 mL and adjusted according to the animal's weighing performed before the procedure. We evaluate the animals through clinical and radiological tests every 7 days. On the 29th day, euthanasia was performed by deep intraperitoneal anesthesia at a dosage of 0.3 ml of Xylazine (80mL/kg) + 0.3 ml of Ketamine (10mg/kg). All biological material was removed by puncture of the aorta, totaling 08-10 mL of blood in tubes containing EDTA. The results demonstrated that doses of the compounds BoEA and ElAc administered in the long term were capable of inducing anti- inflammatory and antinociceptive action evidenced through clinical tests and proved to be decisive in this process, inhibition evidenced by the decrease in serum levels of TNF-α and increase in IL -10 detected after 28 days of treatment. In relation to the radiological and histopathological images of the present study, we observed in the untreated group the presence of exuberant marginal osteophytes, subchondral bone sclerosis, areas of cartilage erosion and medial patellar dislocation, a case very different from the animals that were treated with phytochemical compounds, where they showed reduced progression of joint damage evidenced with lower degrees of joint changes. We concluded that the effects of BoEA and ElAc were able to reduce pain, inhibit the activity of catabolic pathways and consequently, inflammation through regulation and reciprocal balance of anti-inflammatory and pro-inflammatory cytokines in MIA-induced OA, in addition to attenuating the cartilage degeneration evidenced by radiological and histological images.A osteoartrite (OA) é uma patologia caracterizada pela erosão progressiva da cartilagem articular, com alterações estruturais e funcionais concomitantes nos tecidos ao redor das articulações. Nesse contexto, plantas medicinais tornaram-se relevantes ferramentas quanto ao seu potencial papel na prevenção e tratamento da OA, proporcionando uma abordagem terapêutica ou adjuvante segura e eficaz. O objetivo deste estudo foi investigar a eficácia terapêutica da fração acetato de etila das folhas de Bixa orellana (BoEA) e ácido elágico (ElAc) para o tratamento terapêutico de OA induzida por monosodium iodoacetate (MIA) em ratos. Do material vegetal, obtivemos o extrato bruto por maceração com solvente hidroalcóolico 70% (BoHE), seguido de fracionamento com solventes em ordem de polaridade crescente, obtivemos a fração acetato de etila (BoEA). Foi identificado e isolado o composto ElAc na BoEA por meio de cromatografia líquida de alta eficiência (HPLC-PDA) e curva analítica. A OA induzida por MIA foi realizada no joelho direito com volume máximo de 2 mg/25 μL na articulação fêmur tíbio-patelar, através do ligamento patelar. Todos animais foram previamente sedados com o composto de cloridrato de ketamina® 10% (90 mg/kg) para em seguida serem anestesiados por meio de Cloridrato de xilazina® 2% (5 mg/kg) em região intraperitoneal. As doses dos compostos de BoEA e ElAc, assim como da Indometacina e sorbitol foram realizadas via gavagem de 12/12 horas. As gavagens foram realizadas administrando-se volume de 1 mL e ajustada de acordo com a pesagem do animal realizado antes do procedimento. Avaliamos os animais através de testes clínicos e radiológicos a cada 7 dias. No 29o dia foi realizada eutanasia por anestesia profunda em via intraperitoneal na dosagem de 0,3 ml de Xilazina (80mL/kg) + 0,3 ml de Ketamina (10mg/kg). Todo material biológico foi retirado por punção da aorta totalizando 08-10 mL de sangue em tubos contendo EDTA. Os resultados demostraram que doses dos compostos BoEA e ElAc administradas a longo prazo foram capazes de induzir ação anti- inflamatória e antinociceptiva evidenciados através dos testes clínicos e se mostraram determinantes nesse processo inibição evidenciada pela diminuição dos níveis séricos de TNF-α e aumento de IL-10 detectada após 28 dias de tratamento. Em relação às imagens radiológicas e histopatológicas do presente estudo, observamos no grupo não tratado a presença de osteófitos marginais exuberantes, esclerose óssea subcondral, áreas de erosão da cartilagem e luxação patelar medial, caso bem diferente dos animais que foram tratados com os compostos fitoquímicos, onde apresentaram a progressão do dano articular reduzida evidenciado com menores graus de alterações articulares. Concluímos que os efeitos da BoEA e ElAc foram capazes de reduzir a dor, inibir atividade das vias catabólicas e consequentemente, a inflamação por meio de regulação e equilíbrio recíproco de citocinas anti-inflamatórias e pro-inflamatórias em ratos com OA induzida por MIA, além atenuar a degeneração da cartilagem evidenciadas pelas imagens radiológicas e histológicas.Submitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2024-05-13T12:39:26Z No. of bitstreams: 1 LUISÂNGELOMACEDOSANTIAGO.pdf: 3171901 bytes, checksum: 61fb862923f5f3a4feb4292924e6f018 (MD5)Made available in DSpace on 2024-05-13T12:39:26Z (GMT). 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dc.title.por.fl_str_mv A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
dc.title.alternative.eng.fl_str_mv The ethyl acetate fraction of bixa orellana and its isolated compound ellagic acid attenuate the progression of MIA-induced osteoarthritis in rat knees
title A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
spellingShingle A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
SANTIAGO, Luis Ângelo Macedo
degeneração articular;
citocinas;
anti-inflamatório;
analgesia;
antinocicepção.
Joint degeneration;
cytokines;
anti-inflammatory;
analgesia;
antinociception.
Ciências da Saúde
title_short A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
title_full A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
title_fullStr A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
title_full_unstemmed A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
title_sort A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos
author SANTIAGO, Luis Ângelo Macedo
author_facet SANTIAGO, Luis Ângelo Macedo
author_role author
dc.contributor.advisor1.fl_str_mv SOUSA, Eduardo Martins de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/4448263553675550
dc.contributor.referee1.fl_str_mv SOUSA, Eduardo Martins
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/4448263553675550
dc.contributor.referee2.fl_str_mv PESSOA, Débora Luana Ribeiro
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/2537676284852975
dc.contributor.referee3.fl_str_mv COSTA, Adeliane Castro da
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/9373163292240939
dc.contributor.referee4.fl_str_mv COELHO, Marsen Garcia Pinto
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/4468352500732645
dc.contributor.referee5.fl_str_mv MACIEL, Márcia Cristina Gonçalves
dc.contributor.referee5Lattes.fl_str_mv http://lattes.cnpq.br/0645092224285117
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4779581184278191
dc.contributor.author.fl_str_mv SANTIAGO, Luis Ângelo Macedo
contributor_str_mv SOUSA, Eduardo Martins de
SOUSA, Eduardo Martins
PESSOA, Débora Luana Ribeiro
COSTA, Adeliane Castro da
COELHO, Marsen Garcia Pinto
MACIEL, Márcia Cristina Gonçalves
dc.subject.por.fl_str_mv degeneração articular;
citocinas;
anti-inflamatório;
analgesia;
antinocicepção.
topic degeneração articular;
citocinas;
anti-inflamatório;
analgesia;
antinocicepção.
Joint degeneration;
cytokines;
anti-inflammatory;
analgesia;
antinociception.
Ciências da Saúde
dc.subject.eng.fl_str_mv Joint degeneration;
cytokines;
anti-inflammatory;
analgesia;
antinociception.
dc.subject.cnpq.fl_str_mv Ciências da Saúde
description Osteoarthritis (OA) is a pathology characterized by the progressive erosion of articular cartilage, with concomitant structural and functional changes in the tissues around the joints. In this context, medicinal plants have become relevant tools in terms of their potential role in the prevention and treatment of OA, providing a safe and effective therapeutic or adjuvant approach. The aim of this study was to investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of monosodium iodoacetate (MIA)-induced OA in rats. From the plant material, we obtained the crude extract by maceration with 70% hydroalcoholic solvent (BoHE), followed by fractionation with solvents in order of increasing polarity, obtaining the ethyl acetate (BoEA) fraction. The compound ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-PDA) and analytical curve. MIA-induced OA was performed on the right knee with a maximum volume of 2 mg/25 μL at the tibiopatellar femur joint, through the patellar ligament. All animals were previously sedated with ketamine hydrochloride® 10% (90 mg/kg) and then anesthetized using xylazine hydrochloride® 2% (5 mg/kg) in the intraperitoneal region. The doses of BoEA and ElAc compounds, as well as Indomethacin and sorbitol were performed via 12/12 hour gavage. Gavages were performed by administering a volume of 1 mL and adjusted according to the animal's weighing performed before the procedure. We evaluate the animals through clinical and radiological tests every 7 days. On the 29th day, euthanasia was performed by deep intraperitoneal anesthesia at a dosage of 0.3 ml of Xylazine (80mL/kg) + 0.3 ml of Ketamine (10mg/kg). All biological material was removed by puncture of the aorta, totaling 08-10 mL of blood in tubes containing EDTA. The results demonstrated that doses of the compounds BoEA and ElAc administered in the long term were capable of inducing anti- inflammatory and antinociceptive action evidenced through clinical tests and proved to be decisive in this process, inhibition evidenced by the decrease in serum levels of TNF-α and increase in IL -10 detected after 28 days of treatment. In relation to the radiological and histopathological images of the present study, we observed in the untreated group the presence of exuberant marginal osteophytes, subchondral bone sclerosis, areas of cartilage erosion and medial patellar dislocation, a case very different from the animals that were treated with phytochemical compounds, where they showed reduced progression of joint damage evidenced with lower degrees of joint changes. We concluded that the effects of BoEA and ElAc were able to reduce pain, inhibit the activity of catabolic pathways and consequently, inflammation through regulation and reciprocal balance of anti-inflammatory and pro-inflammatory cytokines in MIA-induced OA, in addition to attenuating the cartilage degeneration evidenced by radiological and histological images.
publishDate 2023
dc.date.issued.fl_str_mv 2023-10-31
dc.date.accessioned.fl_str_mv 2024-05-13T12:39:26Z
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.citation.fl_str_mv SANTIAGO, Luis Ângelo Macedo. A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos. 2023. 79 f. Tese (Programa de Pós-Graduação em Rede - Rede de Biodiversidade e Biotecnologia da Amazônia Legal/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.
dc.identifier.uri.fl_str_mv https://tedebc.ufma.br/jspui/handle/tede/tede/5280
identifier_str_mv SANTIAGO, Luis Ângelo Macedo. A fração de acetado de etila de bixa orellana e seu composto isolado ácido elágico atenuam a progressão da osteoartrite induzida por MIA em joelhos de ratos. 2023. 79 f. Tese (Programa de Pós-Graduação em Rede - Rede de Biodiversidade e Biotecnologia da Amazônia Legal/CCBS) - Universidade Federal do Maranhão, São Luís, 2023.
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