Avaliação in vitro do potencial antiglicação do extrato etanólico e de metabólitos de folhas de erva-baleeira (Varronia curassavica Jacq.)
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Data
2022-05-24
Autores
Rodrigues, Winner Duque
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Dentre as plantas de uso medicinal consagrado no Brasil, Varronia curassavica Jacq. (erva-baleeira), uma planta nativa brasileira, é usada no tratamento de processos inflamatórios e de distúrbios gastrointestinais, sendo comercializada em feiras populares e utilizada no preparo de fitoterápicos. O extrato etanólico de suas folhas (EEVc) apresentou atividade anti-inflamatória, antioxidante, efeito protetor gástrico e baixa toxicidade. Na literatura, as plantas medicinais com atividade anti-inflamatória e antioxidante têm despertado interesse frente a atividade antiglicação. A formação de produtos finais de glicação avançada (AGE) ocorre no organismo por fatores diversos. O acúmulo de AGE está associado ao agravo e desencadeamento de diversas doenças crônicas e síndromes metabólicas. Devido aos efeitos acumulativos e deletérios dos AGE, o objetivo deste trabalho foi avaliar o potencial antiglicação do extrato etanólico de V. curassavica e de duas substâncias isoladas. As substâncias utilizadas neste trabalho foram isoladas e purificadas através de técnicas cromatográficas (EFS e HPLC preparativa) e identificados por técnicas espectrométricas UV, MS, IV e RMN de 1H e 13C como uma dihidroxipentametoxiflavona e a cordialina A. Na avaliação do potencial antiglicação foi utilizado um sistema modelo in vitro de incubação de albumina sérica bovina com metilglioxal (37ºC durante 8 dias), seguido de análises de AGE fluorescentes, biomarcadores da oxidação de resíduos de aminoácidos e verificação da formação de ligações cruzadas em proteínas e quantificação de proteína carbonilada (PCO). O EEVc, dihidroxipentametoxiflavona e a cordialina A se mostraram candidatos potencias frente a formação de AGE. O EEVc (250 µg/mL), dihidroxipentametoxiflavona e cordialina A (50 µg/mL) reduziram a formação de AGE em 61,7; 60,8; e 54,9%, respectivamente, no dia 8. Todas as amostras reduziram os prejuízos causados pelo dano oxidativo, que foram determinados pela formação de marcadores de oxidação de resíduos de aminoácidos (ditirosina, N’-formilquinurenina e quinurenina) e pela formação de reticulação proteica (crosslinking proteico), sendo que para PCO a cordialina A (50 µg/mL) foi superior ao padrão. De acordo com os resultados foi observado o potencial antiglicação que as amostras testadas podem promover, o que abre caminho para expandir o arsenal terapêutico para muitas patologias que os AGE estão envolvidos.
Among the plants with established medicinal use in Brazil, Varronia curassavica Jacq. (erva-baleeira), a Brazilian native plant, is used in the treatment of inflammatory processes and gastrointestinal disorders, being commercialized in popular fairs and used in the preparation of phytotherapics. The ethanolic extract of its leaves (EEVc) showed anti-inflammatory activity, antioxidant, gastric protective effect, and low toxicity. In the literature, medicinal plants with anti-inflammatory and antioxidant activity have aroused interest for their anti-glycation activity. The formation of advanced glycation end products (AGE) occurs in the organism by several factors. The accumulation of AGE is associated with the aggravation and triggering of several chronic diseases and metabolic syndromes. Due to the accumulative and deleterious effects of AGE, the objective of this work was to evaluate the antiglycation potential of the ethanolic extract of V. curassavica and two isolated substances. The substances used in this work were isolated and purified by chromatographic techniques (EFS and preparative HPLC) and identified by UV, MS, IR and 1H and 13C NMR spectrometric techniques as a dihydroxypentamethoxyflavone and cordialin A. An in vitro model system of incubation of bovine serum albumin with methylglyoxal (37°C for 8 days), followed by fluorescent AGE analysis, biomarkers of amino acid residue oxidation and verification of cross-link formation in proteins and quantification of carbonylated protein (PCO) was used to evaluate the antiglycation potential. EEVc, dihydroxypentamethoxyflavone and cordialin A were shown to be potential candidates against AGE formation. EEVc (250 µg/mL), dihydroxypentamethoxyflavone and cordialin A (50 µg/mL) reduced AGE formation by 61.7; 60.8; and 54.9%, respectively, on day 8. All samples reduced the damage caused by oxidative damage, which was determined by the formation of markers of oxidation of amino acid residues (dithyrosine, N'-formylquinurenine, and quinurenine) and the formation of protein crosslinking (protein crosslinking), and for PCO cordialin A (50 µg/mL) was higher than the standard. According to the results it was observed the antiglycation potential that the tested samples can promote, which opens the way to expand the therapeutic arsenal for many pathologies that AGEs are involved.
Among the plants with established medicinal use in Brazil, Varronia curassavica Jacq. (erva-baleeira), a Brazilian native plant, is used in the treatment of inflammatory processes and gastrointestinal disorders, being commercialized in popular fairs and used in the preparation of phytotherapics. The ethanolic extract of its leaves (EEVc) showed anti-inflammatory activity, antioxidant, gastric protective effect, and low toxicity. In the literature, medicinal plants with anti-inflammatory and antioxidant activity have aroused interest for their anti-glycation activity. The formation of advanced glycation end products (AGE) occurs in the organism by several factors. The accumulation of AGE is associated with the aggravation and triggering of several chronic diseases and metabolic syndromes. Due to the accumulative and deleterious effects of AGE, the objective of this work was to evaluate the antiglycation potential of the ethanolic extract of V. curassavica and two isolated substances. The substances used in this work were isolated and purified by chromatographic techniques (EFS and preparative HPLC) and identified by UV, MS, IR and 1H and 13C NMR spectrometric techniques as a dihydroxypentamethoxyflavone and cordialin A. An in vitro model system of incubation of bovine serum albumin with methylglyoxal (37°C for 8 days), followed by fluorescent AGE analysis, biomarkers of amino acid residue oxidation and verification of cross-link formation in proteins and quantification of carbonylated protein (PCO) was used to evaluate the antiglycation potential. EEVc, dihydroxypentamethoxyflavone and cordialin A were shown to be potential candidates against AGE formation. EEVc (250 µg/mL), dihydroxypentamethoxyflavone and cordialin A (50 µg/mL) reduced AGE formation by 61.7; 60.8; and 54.9%, respectively, on day 8. All samples reduced the damage caused by oxidative damage, which was determined by the formation of markers of oxidation of amino acid residues (dithyrosine, N'-formylquinurenine, and quinurenine) and the formation of protein crosslinking (protein crosslinking), and for PCO cordialin A (50 µg/mL) was higher than the standard. According to the results it was observed the antiglycation potential that the tested samples can promote, which opens the way to expand the therapeutic arsenal for many pathologies that AGEs are involved.
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Palavras-chave
Varronia curassavica, Atividade antiglicação, Estresse oxidativo, Cordialina A, Dihidroxipentametoxiflavona