Investigação dos mecanismos de ação hipoglicemiante do extratobruto de Bauhinia holophylla em fígado e músculo esquelético de camundongos diabéticos tipo 1 induzidos por estreptozotocina
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Data
2017-01-26
Autores
Camaforte Henriques, Nathalia Aparecida de Paula [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O Diabetes mellitus (DM) é conhecido como uma doença metabólica caracterizada pela hiperglicemia de jejum levando a alterações no metabolismo de carboidratos, lipídeos e proteínas. Nos últimos anos houve um aumento de pesquisas envolvendo plantas medicinais no tratamento de muitas doenças, inclusive DM, no entanto, são poucos os dados que elucidam o mecanismo de ação dessas plantas hipoglicemiantes. O objetivo do presente trabalho foi verificar o mecanismo de ação do extrato bruto de B. holophylla em camundongos diabéticos induzidos por estreptozotocina, avaliando expressão gênica e proteica da via de sinalização de insulina em tecidos periféricos como fígado e músculo esquelético, bem como avaliar a atividade inibitória para as enzimas α- amilases e α-glicosidades em testes in vitro e in vivo. O tratamento com o extrato de B. holophylla promoveu a diminuição da expressão gênica e proteica das enzimas G6Pase, PEPCK e Glicogênio Fosforilase e aumento da expressão proteica AMPK em fígado. Em músculo, promoveu o aumento da expressão das proteínas PI3K, AKT e GLUT4 e diminuição da expressão da PTP1B. Além disso, o extrato mostrou potente atividade inibitória para as enzimas α-amilases e α-glicosidases in vitro e in vivo. Portanto, conclui-se que a atividade hipoglicemiante do extrato de B. holophylla foi através da ativação da via da glicogênese e inibição da gliconeogêse e glicogenólise em fígado, ativando as vias dependente e independente de insulina para captação de glicose em músuclo esquelético e inibindo a absorção de glicose no intestino.
Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia (equal or higher than 126 mg/dL) resulting in alterations on fatty, protein and carbohydrate metabolism. In the past years many researches of medicinal plants area to treat a great sort of diseases, including DM was done, however, there are few data with the elucidation of mechanism of action of these medicinal plants. The aim of this study was to verify the hypoglycemic mechanism of action of B. holophylla in streptozotocin diabetic mice, evaluating key-proteins and gene expression from insulin pathway in muscle and liver, and the inhibitory effect for the α-amylases and α-glucosidases in vitro and in vivo tests. We also tested the hypoglycemic effect of fractions and the isolated compound by the crude extract of B. holophylla. The treatment with the extract of B. holophylla, the gene and protein expression analysis showed a decrease of G6Pase, PEPCK and increase of AMPK and GSk3β in liver. In muscle, the treatment was able to increase the PI3K, AKT and GLUT4 and decrease of PTP1B protein expression. Beyond this, the extract showed potent inhibitory effect against α-amylases and α-glucosidases in in vitro and in vivo tests. In conclusion, the mechanism of hypoglycemic action of B. holophylla was activating glycogenesis and inhibiting gluconeogenesis and glycogenolisis in liver, activating dependents and independent insulin pathway for glucose intake in muscle and decreasing the glucose absorption in intestine.
Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia (equal or higher than 126 mg/dL) resulting in alterations on fatty, protein and carbohydrate metabolism. In the past years many researches of medicinal plants area to treat a great sort of diseases, including DM was done, however, there are few data with the elucidation of mechanism of action of these medicinal plants. The aim of this study was to verify the hypoglycemic mechanism of action of B. holophylla in streptozotocin diabetic mice, evaluating key-proteins and gene expression from insulin pathway in muscle and liver, and the inhibitory effect for the α-amylases and α-glucosidases in vitro and in vivo tests. We also tested the hypoglycemic effect of fractions and the isolated compound by the crude extract of B. holophylla. The treatment with the extract of B. holophylla, the gene and protein expression analysis showed a decrease of G6Pase, PEPCK and increase of AMPK and GSk3β in liver. In muscle, the treatment was able to increase the PI3K, AKT and GLUT4 and decrease of PTP1B protein expression. Beyond this, the extract showed potent inhibitory effect against α-amylases and α-glucosidases in in vitro and in vivo tests. In conclusion, the mechanism of hypoglycemic action of B. holophylla was activating glycogenesis and inhibiting gluconeogenesis and glycogenolisis in liver, activating dependents and independent insulin pathway for glucose intake in muscle and decreasing the glucose absorption in intestine.
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Palavras-chave
Cerrado, Doença metabólica, Fitoterapia, Hipoglicemiante, Plantas medicinais