Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites

Detalhes bibliográficos
Autor(a) principal: Jaiyesimi, Olakunle Adeboye
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: eng
Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
Texto Completo: https://www.teses.usp.br/teses/disponiveis/60/60138/tde-27092021-103645/
Resumo: Chronic hyperglycemia in the prediabetic stage leads to glucose toxicity and pancreatic β-islet cells damage due to oxidative stress, predisposing subjects to the developement of type 2 diabetes. As a significant global health challenge, the continued search for phytoconstituents with potential to prevent, reduce or delay hyperglycemia and its ultimate progression to type 2 diabetes, amongst other benefits including reduced or absence of side effects, is warranted. This study evaluated 68 Asteraceae species for their in vitro ability to improve glucose-uptake, inhibit both fungal (from Aspergillus oryzae) and porcine pancreatic α-amylases, retard glucose diffusion and scavenge DPPH free radicals. Of the plants investigated, 11 retarded glucose diffusion with Senecio biafrae, Eremanthus veadeiroensis and Vernonia brasiliana being the most active; 37 inhibited fungal α-amylase including Silybum marianum, Acanthospermum hispidum and Nigerian Tithonia diversifolia; 12 inhibited porcine pancreatic α-amylase with the most active being S. marianum, Baccharis gaudichaudiana and Eremanthus veadeiroensis; 36 improved insulin-mediated glucose uptake significantly better than metformin including Micania micrantha, Crassocephalum crepidioides and E. veadeiroensis; and 6 significantly exhibited > 90.0% antioxidant activity including Arnica montana, Baccharis genistelloides, B. gaudichaudiana, Erigeron floribundus, Solidago microglossa and Achillea millefolium. All the extracts were analysed by LC-UV-MS for further metabolomics analyses. The LC-MS chromatograms were processed and the generated marices were analyzed by unsupervised (Hierachical Cluster Analysis and Principal Component Analysis) and supervised (Partial least squarediscriminant analysis) multivariate statistical analysis. Untargeted metabolomics, correlating the metabolic fingerprints with the plants\' observed bioactivities, yielded significant discriminant metabolites for each assay. Flavonoids and their glycosides were revealed as important variables responsible for the antidiabetic as well as antioxidant activities, indicating additional potential for the prevention of diabetes. Such includes apigenin 6-C-arabinoside8-C-glucoside, 6-methoxykaempferol-3-O-glucoside, 5-hydroxy-3,6,7,4\'- tetramethoxyflavone, 5,6,7,4\'-tetramethoxyflavone and 3,4\',6-trimethoxyquercetagetin. This study provides further evidence for the use of untargeted metabolomics for the rapid determination of plant specialized metabolites with bioactive potentials, in this case the reduction or prevention of hyperglycaemia.
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spelling Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolitesAnálise metabólica de espécies de Asteraceae brasileiras e nigerianas, visando metabólitos moduladores da hiperglicemiaAsteraceaeAsteraceaeEspectrometria de massasHiperglicemia pósprandiaMass spectrometryMetabolômica não segmentadaPostprandia hyperglycemiaPré-diabetesPrediabetesUntargeted metabolomicsChronic hyperglycemia in the prediabetic stage leads to glucose toxicity and pancreatic β-islet cells damage due to oxidative stress, predisposing subjects to the developement of type 2 diabetes. As a significant global health challenge, the continued search for phytoconstituents with potential to prevent, reduce or delay hyperglycemia and its ultimate progression to type 2 diabetes, amongst other benefits including reduced or absence of side effects, is warranted. This study evaluated 68 Asteraceae species for their in vitro ability to improve glucose-uptake, inhibit both fungal (from Aspergillus oryzae) and porcine pancreatic α-amylases, retard glucose diffusion and scavenge DPPH free radicals. Of the plants investigated, 11 retarded glucose diffusion with Senecio biafrae, Eremanthus veadeiroensis and Vernonia brasiliana being the most active; 37 inhibited fungal α-amylase including Silybum marianum, Acanthospermum hispidum and Nigerian Tithonia diversifolia; 12 inhibited porcine pancreatic α-amylase with the most active being S. marianum, Baccharis gaudichaudiana and Eremanthus veadeiroensis; 36 improved insulin-mediated glucose uptake significantly better than metformin including Micania micrantha, Crassocephalum crepidioides and E. veadeiroensis; and 6 significantly exhibited > 90.0% antioxidant activity including Arnica montana, Baccharis genistelloides, B. gaudichaudiana, Erigeron floribundus, Solidago microglossa and Achillea millefolium. All the extracts were analysed by LC-UV-MS for further metabolomics analyses. The LC-MS chromatograms were processed and the generated marices were analyzed by unsupervised (Hierachical Cluster Analysis and Principal Component Analysis) and supervised (Partial least squarediscriminant analysis) multivariate statistical analysis. Untargeted metabolomics, correlating the metabolic fingerprints with the plants\' observed bioactivities, yielded significant discriminant metabolites for each assay. Flavonoids and their glycosides were revealed as important variables responsible for the antidiabetic as well as antioxidant activities, indicating additional potential for the prevention of diabetes. Such includes apigenin 6-C-arabinoside8-C-glucoside, 6-methoxykaempferol-3-O-glucoside, 5-hydroxy-3,6,7,4\'- tetramethoxyflavone, 5,6,7,4\'-tetramethoxyflavone and 3,4\',6-trimethoxyquercetagetin. This study provides further evidence for the use of untargeted metabolomics for the rapid determination of plant specialized metabolites with bioactive potentials, in this case the reduction or prevention of hyperglycaemia.A hiperglicemia crônica no estágio pré-diabético acarreta toxicidade à glicose e dano às células β-ilhotas pancreáticas devido ao estresse oxidativo, predispondo os indivíduos ao desenvolvimento de diabetes tipo 2. Como um desafio significativo para a saúde global, a busca contínua de fitoconstituintes com potencial para prevenir, reduzir ou retardar a hiperglicemia e sua progressão final para o diabetes tipo 2, entre outros benefícios, é justificada. Este estudo avaliou 68 espécies de Asteraceae por sua capacidade in vitro de melhorar a captação de glicose, inibir as α-amilases pancreáticas de suínos (de Aspergillus oryzae) e porcinos, retardar a difusão da glicose e eliminar os radicais livres de DPPH. Das plantas investigadas, 11 retardaram a difusão da glicose, com Senecio biafrae, Eremanthus veadeiroensis e Vernonia brasiliana sendo as mais ativas; 37 inibiram a α-amilase fúngica, incluindo Silybum marianum, Acanthospermum hispidum e Tithonia diversifolia (nigeriana); 12 inibiram a α-amilase pancreática porcina sendo os mais ativos S. marianum, Baccharis gaudichaudiana e E. veadeiroensis; 36 melhoraram a captação de glicose mediada por insulina significativamente melhor que a metformina, incluindo Micania micrantha, Crassocephalum crepidioides e E. veadeiroensis; e 6 exibiram significativamente > 90,0% de atividade antioxidante incluindo Arnica montana, Baccharis genistelloides, B. gaudichaudiana, Erigeron floribundus, Solidago microglossa e Achillea millefolium. As matrizes MzmineTM geradas pré-processadas das impressões digitais metabólicas de extratos vegetais obtidos com UHPLC -UV(DAD)-MS (Orbitrap) foram analisadas no SIMCA utilizando-se análise não supervisionada (Análise de Agrupamento Hieráquico e Análise de Componentes Principais) e supervisionadas análise estatística multivariada. A metabolômica não-alvo, correlacionando as impressões digitais metabólicas com as bioatividades observadas nas plantas, produziu metabólitos discriminantes significativos para cada ensaio. Os flavonóides e seus glicosídeos foram revelados como importantes variáveis responsáveis pelas atividades antidiabéticas e antioxidantes, indicando potencial adicional para a prevenção do diabetes. Tal inclui a apigenina 6-C-arabinoside-8-Cglicosídeo, kaempferol-6-metoxi-3-O-glicosídeo, 5-hidroxi-3,6,7,4\'-tetrametoxiflavona, 5,6,7,4\'-tetrametoxiflavona e 3,4\',6-trimetoxiquercetagetina. Este estudo fornece mais evidências para o uso de metabolômica não direcionada para a rápida determinação de metabólitos especializados em plantas com potenciais bioativos, neste caso a redução ou a prevenção da hiperglicemia.Biblioteca Digitais de Teses e Dissertações da USPGobbo Neto, LeonardoRechia, Carem Gledes VargasJaiyesimi, Olakunle Adeboye2019-09-06info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/60/60138/tde-27092021-103645/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2024-09-02T17:15:33Zoai:teses.usp.br:tde-27092021-103645Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212024-09-02T17:15:33Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
Análise metabólica de espécies de Asteraceae brasileiras e nigerianas, visando metabólitos moduladores da hiperglicemia
title Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
spellingShingle Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
Jaiyesimi, Olakunle Adeboye
Asteraceae
Asteraceae
Espectrometria de massas
Hiperglicemia pósprandia
Mass spectrometry
Metabolômica não segmentada
Postprandia hyperglycemia
Pré-diabetes
Prediabetes
Untargeted metabolomics
title_short Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
title_full Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
title_fullStr Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
title_full_unstemmed Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
title_sort Metabolomics analysis of Brazilian and Nigerian Asteraceae species, targeting hyperglycemia-modulating metabolites
author Jaiyesimi, Olakunle Adeboye
author_facet Jaiyesimi, Olakunle Adeboye
author_role author
dc.contributor.none.fl_str_mv Gobbo Neto, Leonardo
Rechia, Carem Gledes Vargas
dc.contributor.author.fl_str_mv Jaiyesimi, Olakunle Adeboye
dc.subject.por.fl_str_mv Asteraceae
Asteraceae
Espectrometria de massas
Hiperglicemia pósprandia
Mass spectrometry
Metabolômica não segmentada
Postprandia hyperglycemia
Pré-diabetes
Prediabetes
Untargeted metabolomics
topic Asteraceae
Asteraceae
Espectrometria de massas
Hiperglicemia pósprandia
Mass spectrometry
Metabolômica não segmentada
Postprandia hyperglycemia
Pré-diabetes
Prediabetes
Untargeted metabolomics
description Chronic hyperglycemia in the prediabetic stage leads to glucose toxicity and pancreatic β-islet cells damage due to oxidative stress, predisposing subjects to the developement of type 2 diabetes. As a significant global health challenge, the continued search for phytoconstituents with potential to prevent, reduce or delay hyperglycemia and its ultimate progression to type 2 diabetes, amongst other benefits including reduced or absence of side effects, is warranted. This study evaluated 68 Asteraceae species for their in vitro ability to improve glucose-uptake, inhibit both fungal (from Aspergillus oryzae) and porcine pancreatic α-amylases, retard glucose diffusion and scavenge DPPH free radicals. Of the plants investigated, 11 retarded glucose diffusion with Senecio biafrae, Eremanthus veadeiroensis and Vernonia brasiliana being the most active; 37 inhibited fungal α-amylase including Silybum marianum, Acanthospermum hispidum and Nigerian Tithonia diversifolia; 12 inhibited porcine pancreatic α-amylase with the most active being S. marianum, Baccharis gaudichaudiana and Eremanthus veadeiroensis; 36 improved insulin-mediated glucose uptake significantly better than metformin including Micania micrantha, Crassocephalum crepidioides and E. veadeiroensis; and 6 significantly exhibited > 90.0% antioxidant activity including Arnica montana, Baccharis genistelloides, B. gaudichaudiana, Erigeron floribundus, Solidago microglossa and Achillea millefolium. All the extracts were analysed by LC-UV-MS for further metabolomics analyses. The LC-MS chromatograms were processed and the generated marices were analyzed by unsupervised (Hierachical Cluster Analysis and Principal Component Analysis) and supervised (Partial least squarediscriminant analysis) multivariate statistical analysis. Untargeted metabolomics, correlating the metabolic fingerprints with the plants\' observed bioactivities, yielded significant discriminant metabolites for each assay. Flavonoids and their glycosides were revealed as important variables responsible for the antidiabetic as well as antioxidant activities, indicating additional potential for the prevention of diabetes. Such includes apigenin 6-C-arabinoside8-C-glucoside, 6-methoxykaempferol-3-O-glucoside, 5-hydroxy-3,6,7,4\'- tetramethoxyflavone, 5,6,7,4\'-tetramethoxyflavone and 3,4\',6-trimethoxyquercetagetin. This study provides further evidence for the use of untargeted metabolomics for the rapid determination of plant specialized metabolites with bioactive potentials, in this case the reduction or prevention of hyperglycaemia.
publishDate 2019
dc.date.none.fl_str_mv 2019-09-06
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://www.teses.usp.br/teses/disponiveis/60/60138/tde-27092021-103645/
url https://www.teses.usp.br/teses/disponiveis/60/60138/tde-27092021-103645/
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv
dc.rights.driver.fl_str_mv Liberar o conteúdo para acesso público.
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Liberar o conteúdo para acesso público.
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.coverage.none.fl_str_mv
dc.publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
dc.source.none.fl_str_mv
reponame:Biblioteca Digital de Teses e Dissertações da USP
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Biblioteca Digital de Teses e Dissertações da USP
collection Biblioteca Digital de Teses e Dissertações da USP
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)
repository.mail.fl_str_mv virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br
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