Orientador: Thais Borges César / Coorientador:Paulo Inácio da Costa / Banca: Neuza Mariko Aymoto Hassimotto / Banca: Alceu Afonso Jordão Jr. / Banca: Amanda Martins Baviera / Banca: Célia Maria de Sylos / Resumo: As polimetoxiflavonas (PMF) são uma subclasse do grupo dos flavonoides cítricos, as quais são conhecidas devido à ação antioxidante, anti-inflamatória, hipolipidêmica e anticâncer; além de elevada biodisponibilidade. Estudos recentes demonstram que os metabólitos gerados a partir das PMF são biologicamente ativos, e possuem efeitos benéficos superiores aos compostos originais. Objetivo: Este trabalho teve por objetivo, isolar e identificar metabólitos das PMF a partir da urina de ratos, e avaliar sua atividade biológica sobre a proteína transferidora de triglicerídeo microssomal (MTP) em células Huh7.5. Métodos: Trinta ratos Wistar adultos foram separados em 3 grupos (n = 10) e administrados com 200 mg/kg/dia de tangeretina (TAN), nobiletina (NOB) ou heptametoxiflavona (HMF), durante 15 dias. Os metabólitos foram extraídos da urina, isolados por cromatografia líquida preparativa, e identificados por cromatografia líquida de alta eficiência (HPLC-ESI-MS) acoplada ao detector de UV (PDA). A ação dos metabólitos sobre a atividade da MTP foi avaliada por método fluorométrico. Resultados: Foram isolados metabólitos glucuronídeos com m/z [M+H]+ 565 amu (unidade de massa atômica), 551 amu, 535 amu, 521 amu, 505 amu; além de metabólitos hidroxilados com m/z [M+H]+ 419 amu, 405 amu, 389 amu, 375 amu, 359 amu, 329 amu, 315 amu. Os metabólitos TAN-4'-glucuronídeo (TAN-G1), TAN-dihidroxi-glucuronídeo (TAN-G2), TAN-4'-monohidroxilada (TAN-OH1), TAN-monohidroxilada (TAN-OH2), NOB-glucuroní... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The polymethoxylated flavones (PMF) are a subclass of flavonoids citrus, which are known because of their antioxidant, anti-inflammatory, hypolipidemic and anticancer properties; besides the high bioavailability that they present. Recent studies show that the metabolites generated from the PMF are biologically active and have beneficial effects greater than the original compounds. Objective: This study aimed to isolate and identify metabolites of PMF from the urine of rats, and evaluate its biological activity upon microsomal triglyceride transfer protein (MTP) in Huh7.5 cells. Methods: Thirty adult male Wistar rats were separated into 3 groups (n = 10) and fed with 200 mg / kg / day with tangeretin (TAN), nobiletina (NOB) or heptametoxiflavona (HMF) for 15 days. The metabolites were extracted from urine, isolated by preparative liquid chromatography and identified by high-performance liquid chromatography (HPLC-ESI-MS) coupled with UV detector (PDA). The action of the metabolites on the MTP activity was evaluated by fluorometric method. Results: We isolated glucuronide metabolites with m / z [M + H] + 565 amu (atomic mass unit), 551 amu, 535 amu, 521 amu, 505 amu; addition to the hydroxilated metabolites with m / z [M + H] + 419 amu, 405 amu, 389 amu, 375 amu, 359 amu, 329 amu, 315 amu. The TAN-4'-glucuronide metabolites (TAN-G1), TAN-dihydroxyglucuronide (TAN-G2), TAN-4'-monohidroxilada (TAN-OH1), TAN-monohydroxylada (TAN-OH2), NOB-glucuronide (NOB-G) NOB-monohydroxylada (NOB-OH), HMFmonohydroxylada (HMF-OH) have been identified and evaluated in in vitro assay. TAN-OH1 and NOB-OH reduced the MTP activity, and HMF-OH showed higher effect compared to its parent compound. PMF obtained from dry extract of orange peel, administered in rats, showed no effect on the MTP. Conclusion: These data show viable methods for isolation of the... (Complete abstract click electronic access below) / Doutor
| Identifer | oai:union.ndltd.org:UNESP/oai:www.athena.biblioteca.unesp.br:UEP01-000876898 |
| Date | January 2016 |
| Creators | Gonçalves, Danielle Raquel. |
| Contributors | Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Ciências Farmacêuticas. |
| Publisher | Araraquara, |
| Source Sets | Universidade Estadual Paulista |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | text |
| Format | 116 f. : |
| Relation | Sistema requerido: Adobe Acrobat Reader |
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