Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg
Hypertension and Diabetes Mellitus are diseases on the rise in the world and can cause several cardiovascular complications. Several drugs have efficacy in the treatment of these diseases, however, many have adverse effects and limitations of efficacy. The peel of the fruit of P. edulis f. flavic...
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Passiflora edulis f flavicarpa Pericarpo Flavonoides Toxicidade Hipertensão Diabetes Fitoterápicos |
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Passiflora edulis f flavicarpa Pericarpo Flavonoides Toxicidade Hipertensão Diabetes Fitoterápicos Cabral, Bárbara Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg |
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Hypertension and Diabetes Mellitus are diseases on the rise in the world and can cause several
cardiovascular complications. Several drugs have efficacy in the treatment of these diseases,
however, many have adverse effects and limitations of efficacy. The peel of the fruit of P. edulis
f. flavicarpa O. Degener (yellow passion fruit), considered a waste from the food industry, is
rich in bioactive compounds. Thus, due to the need to search for new treatments for
hypertension and diabetes, and in order to stimulate the development of herbal medicines with
species native to Brazil, the study aimed to evaluate the phytochemical composition, the toxicity
profile and the pharmacological potential of P. edulis peel extracts in non-clinical models of
hypertension and diabetes. Methodology was divided into the following parts: i: phytochemical
study, assessment of antioxidant activity in vitro and acute oral toxicity ii: non-clinical
assessment of antihypertensive activity in an ex vivo model of isolated arteries and in chronic
model of spontaneously hypertensive rats; iii acute and chronic non-clinical evaluation of
antidiabetic activity in models of type 1 diabetes, induced by streptozotocin. Two extracts were
produced (aqueous, prepared by decoction-AFA and hydroethanolic -AFM, obtained by
maceration) from the peel flour (dry and crushed peel) of P. edulis. Phytochemical analysis was
performerd by CCD, UHPLC/UV-DAD and HPLC-ESI-MSn. In both extracts C-glycosylated
flavonoids were identified. Among the identified flavonoids, it was possible to quantify the
content of vicenin-2, orientin, isoorientin, vitexin and isovitexin by HPLC-QqQ-MS/MS. The
polysaccharide pectin was found only in the AFA extract, through high performance steric
exclusion chromatography and NMR, its content was 34.3%. According to the results obtained
in acute oral toxicity, extracts were classified in category 5 by GSH (Globally Harmonized
Classification System for Chemical Substances and Mixtures) with LD50> 2000mg/kg, since
they did not show signs of acute toxicity. The in vitro antioxidant assay showed that the extracts
have good antioxidant activity observed by TAC, reducing power and DPPH tests. In the
evaluation of the antihypertensive effect, it was verified in an ex vivo model of isolated artery
that the AFM extract had the best relaxation profile, when compared to AFA. It effect may be
due to the opening of the potassium channels. In addition, the AFM extract at doses 200 and
400 mg/kg, orally, showed a significant hypotensive effect after 28 days of treatment and
improved vascular function in the mesenteric artery. This was verified by a decrease in vascular
hypercontractility and an increase in the vasorelaxant effect in response to sodium nitroprusside
and acetylcholine. There was also a decrease in endothelial dysfunction that can be attributed
to the increased bioavailability of nitric oxide. Thus, our hypothesis is that all these effects were
able to contribute to the reduction of peripheral vascular resistance, causing a significant
hypotensive effect. These results are unprecedented for the pericarp of P. edulis. In addition,
there was a decrease in plasma MDA levels in the heart and an increase in glutathione,
suggesting a decrease in oxidative stress, as well as an increase in plasma of anti-inflammatory
cytokines such as IL-10. In the acute in vivo antidiabetic model, it was observed that the extracts
at doses of 400 and 600 mg/kg associated with insulin were able to significantly reduce blood
glucose, when compared to diabetic rats that received only insulin, being this effect more
significant with AFA treatment. In the chronic antidiabetic model, the treatment with the
extracts during 60 days caused a significant reduction in glycemia observed at a dose of 400
mg/kg. In addition, extracts decreased MDA in the liver and MPO in the heart and kidney,
suggesting that the extracts may act by reducing oxidative stress and inflammation caused in
diabetes. Renal fibrosis was also reduced with chronic treatment. Taken together, toxicological
and pharmacological studies proved the safe and the potential effect of P.edulis peel fruit
extracts in development new phytoterapics. |
| author2 |
Langassner, Silvana Maria Zucolotto |
| author_facet |
Langassner, Silvana Maria Zucolotto Cabral, Bárbara |
| format |
doctoralThesis |
| author |
Cabral, Bárbara |
| author_sort |
Cabral, Bárbara |
| title |
Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg |
| title_short |
Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg |
| title_full |
Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg |
| title_fullStr |
Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg |
| title_full_unstemmed |
Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg |
| title_sort |
avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de passiflora edulis f. flavicarpa o. deg |
| publisher |
Universidade Federal do Rio Grande do Norte |
| publishDate |
2020 |
| url |
https://repositorio.ufrn.br/handle/123456789/31014 |
| work_keys_str_mv |
AT cabralbarbara avaliacaodacomposicaoquimicaedoperfiltoxicologicoefarmacologicodosextratosobtidosdoresiduoindustrialdosfrutosdepassifloraedulisfflavicarpaodeg |
| _version_ |
1797696507805171712 |
| spelling |
ri-123456789-310142024-03-19T04:03:39Z Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg Cabral, Bárbara Langassner, Silvana Maria Zucolotto http://lattes.cnpq.br/2236334270659871 http://lattes.cnpq.br/7390416147619446 Rezende, Adriana Augusto de http://lattes.cnpq.br/4245215108740331 Silva Júnior, Edilson Dantas da Ferreira, Leandro de Santis http://lattes.cnpq.br/6622861873027635 Baratto, Leopoldo Clemente http://lattes.cnpq.br/9495378271045592 Espindola, Foued Salmen http://lattes.cnpq.br/0692083522907038 Passiflora edulis f flavicarpa Pericarpo Flavonoides Toxicidade Hipertensão Diabetes Fitoterápicos Hypertension and Diabetes Mellitus are diseases on the rise in the world and can cause several cardiovascular complications. Several drugs have efficacy in the treatment of these diseases, however, many have adverse effects and limitations of efficacy. The peel of the fruit of P. edulis f. flavicarpa O. Degener (yellow passion fruit), considered a waste from the food industry, is rich in bioactive compounds. Thus, due to the need to search for new treatments for hypertension and diabetes, and in order to stimulate the development of herbal medicines with species native to Brazil, the study aimed to evaluate the phytochemical composition, the toxicity profile and the pharmacological potential of P. edulis peel extracts in non-clinical models of hypertension and diabetes. Methodology was divided into the following parts: i: phytochemical study, assessment of antioxidant activity in vitro and acute oral toxicity ii: non-clinical assessment of antihypertensive activity in an ex vivo model of isolated arteries and in chronic model of spontaneously hypertensive rats; iii acute and chronic non-clinical evaluation of antidiabetic activity in models of type 1 diabetes, induced by streptozotocin. Two extracts were produced (aqueous, prepared by decoction-AFA and hydroethanolic -AFM, obtained by maceration) from the peel flour (dry and crushed peel) of P. edulis. Phytochemical analysis was performerd by CCD, UHPLC/UV-DAD and HPLC-ESI-MSn. In both extracts C-glycosylated flavonoids were identified. Among the identified flavonoids, it was possible to quantify the content of vicenin-2, orientin, isoorientin, vitexin and isovitexin by HPLC-QqQ-MS/MS. The polysaccharide pectin was found only in the AFA extract, through high performance steric exclusion chromatography and NMR, its content was 34.3%. According to the results obtained in acute oral toxicity, extracts were classified in category 5 by GSH (Globally Harmonized Classification System for Chemical Substances and Mixtures) with LD50> 2000mg/kg, since they did not show signs of acute toxicity. The in vitro antioxidant assay showed that the extracts have good antioxidant activity observed by TAC, reducing power and DPPH tests. In the evaluation of the antihypertensive effect, it was verified in an ex vivo model of isolated artery that the AFM extract had the best relaxation profile, when compared to AFA. It effect may be due to the opening of the potassium channels. In addition, the AFM extract at doses 200 and 400 mg/kg, orally, showed a significant hypotensive effect after 28 days of treatment and improved vascular function in the mesenteric artery. This was verified by a decrease in vascular hypercontractility and an increase in the vasorelaxant effect in response to sodium nitroprusside and acetylcholine. There was also a decrease in endothelial dysfunction that can be attributed to the increased bioavailability of nitric oxide. Thus, our hypothesis is that all these effects were able to contribute to the reduction of peripheral vascular resistance, causing a significant hypotensive effect. These results are unprecedented for the pericarp of P. edulis. In addition, there was a decrease in plasma MDA levels in the heart and an increase in glutathione, suggesting a decrease in oxidative stress, as well as an increase in plasma of anti-inflammatory cytokines such as IL-10. In the acute in vivo antidiabetic model, it was observed that the extracts at doses of 400 and 600 mg/kg associated with insulin were able to significantly reduce blood glucose, when compared to diabetic rats that received only insulin, being this effect more significant with AFA treatment. In the chronic antidiabetic model, the treatment with the extracts during 60 days caused a significant reduction in glycemia observed at a dose of 400 mg/kg. In addition, extracts decreased MDA in the liver and MPO in the heart and kidney, suggesting that the extracts may act by reducing oxidative stress and inflammation caused in diabetes. Renal fibrosis was also reduced with chronic treatment. Taken together, toxicological and pharmacological studies proved the safe and the potential effect of P.edulis peel fruit extracts in development new phytoterapics. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES A hipertensão e a Diabetes Mellitus são doenças em ascensão no mundo e podem causar várias complicações cardiovasculares. Diversos fármacos apresentam eficácia no tratamento dessas doenças, entretanto, muitos apresentam efeitos adversos e limitações de eficácia. O pericarpo do fruto de P. edulis f. flavicarpa O. Degener (maracujá amarelo), considerado um resíduo da indústria alimentícia é rico em compostos bioativos. Assim, devido à necessidade da busca por novos tratamentos para a hipertensão e diabetes, e com o intuito de estimular o desenvolvimento de fitoterápicos com espécies nativas do Brasil, o estudo teve como objetivo avaliar a composição fitoquímica, o perfil de toxicidade e o potencial efeito farmacológico de extratos do pericarpo em modelo não clínico de hipertensão e de diabetes. Para atingir os objetivos, a metodologia do estudo foi dividida nas seguintes partes: i: estudo fitoquímico, avaliação da atividade antioxidante in vitro e a avaliação da toxicidade oral aguda ii: avaliação não clínica da atividade antihipertensiva em modelo ex vivo de artérias isoladas e em modelo crônico de ratos espontaneamente hipertensos; iii avaliação não clínica aguda e crônica da atividade antidiabética em modelos de diabetes tipo 1, induzido por streptozotocina. Para o desenvolvimento do estudo foram produzidos dois extratos, um aquoso, preparado por decocção (AFA) e um hidroetanólico (AFM), obtido por maceração, a partir da farinha do pericarpo (pericarpo seco e triturado) de P. edulis. Os metabólitos secundários dos extratos foram identificados por CCD, CLUE-UV/DAD e CLAE-ESI-MSn , sendo os flavonoides Cglicosilados os metabólitos secundários mais encontrados em AFA e AFM. Dentre os flavonoides identificados, foi possível quantificar o teor de vicenina-2, orientina, isoorientina, vitexina e isovitexina por CLAE-QqQ-MS/MS. O polissacarídeo pectina foi encontrado apenas no extrato AFA, através de cromatografia de exclusão estérica de alto desempenho e RMN, o seu teor foi de 34,3%. De acordo com os resultados obtidos da avaliação da toxicidade oral aguda, os extratos AFA e AFM foram classificados na categoria 5 pelo GSH (Globally Harmonised Classification System for Chemical Substances and Mixtures) com DL50 >2000mg/kg, visto que, não apresentaram sinais de toxicidade aguda. O ensaio de avaliação antioxidante in vitro mostrou que os extratos têm boa atividade antioxidante pelos ensaios de CAT, poder redutor e DPPH. Na avaliação do efeito antihipertensivo foi verificado em modelo ex vivo de artéria isolada que o extrato AFM apresentou o melhor perfil de vasorelaxamento, quando comparado com AFA, esse efeito pode ser devido à abertura dos canais de potássio. Além disso, o extrato AFM nas doses 200 e 400 mg/Kg mostrou efeito hipotensivo significativo após 28 dias de tratamento e melhorou a função vascular em artéria mesentérica. Isso foi verificado pela diminuição da hipercontratilidade vascular e aumento do efeito vasorelaxante em resposta ao nitroprussiato de sódio e a Acetilcolina. Houve também uma diminuição na disfunção endotelial que pode ser atribuída ao aumento da biodisponibilidade do óxido nítrico. Assim, nossa hipótese é que todos esses efeitos foram capazes de contribuir para a redução da resistência vascular periférica, causando um efeito hipotensivo significativo. Estes resultados são inéditos para o pericarpo de P. edulis. Além disso, houve uma diminuição nos níveis plasmáticos de MDA no coração e um aumento da glutationa, sugerindo uma diminuição no estresse oxidativo, bem como um aumento no plasma de citocinas anti-inflamatórias como a IL-10. Na avaliação aguda da atividade antidiabética, observou-se que os extratos AFA e AFM nas doses de 400 e 600 mg/Kg de forma adjuvante a insulina conseguiram reduzir de forma significativa a glicemia, quando comparado aos ratos diabéticos que receberam apenas a insulina, sendo esse efeito mais significativo com tratamento com AFA. No estudo crônico de 60 dias esse efeito foi confirmado sendo observado uma redução significativa da glicemia com o tratamento dos extratos AFA e AFM na dose de 400 mg/Kg. Foi verificado ainda uma diminuição do MDA no fígado e uma dimunição de MPO no coração e rim, sugerindo que os extratos podem agir diminuindo o extresse oxidativo e a inflamação ocasionada na diabetes. A fibrose renal também foi diminuída com o tratamento crônico. Portanto, os estudos toxicológicos e farmacológicos apontaram que o extrato AFA e AFM, obtido de um resíduo industrial mostrou-se seguro e tem potencial para a obtenção de novos fitoterápicos com ação na hipertensão e na diabetes tipo 1. 2021-10-19 2020-12-15T23:20:57Z 2020-08-28 doctoralThesis CABRAL, Bárbara. Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg. 2020. 198f. Tese (Doutorado em Ciências Farmacêuticas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2020. https://repositorio.ufrn.br/handle/123456789/31014 pt_BR Acesso Embargado application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS FARMACÊUTICAS |