Hypoglycaemic activity of Bauhinia holophylla through GSK3-beta inhibition and glycogenesis activation

• Autor(a) principal: De Paula Camaforte, Nathalia Ap [UNESP]
• Data de Publicação: 2019
• Outros Autores: Saldanha, Luiz Leonardo [UNESP], Ponce Vareda, Priscilla Maria [UNESP], Rezende-Neto, Joao M., Senger, Mario R., Delgado, Aislan Q. [UNESP], Morgan, Henrique J. N. [UNESP], Violato, Natalia Moretti [UNESP], Pieroni, Lais Goyos [UNESP], Dokkedal, Anne Ligia [UNESP], Silva, Floriano P., Bosqueiro, Jose Roberto [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1080/13880209.2019.1599962; http://hdl.handle.net/11449/185627
• topic: Antidiabetic; Fabaceae; flavonoid-O-glycosides; liver; plasma lipids

Context: Bauhinia L. species, including Bauhinia holophylla (Bong.) Steud. (Fabaceae), have traditionally been used to treat diabetes. Bauhinia is a complex botanical genus, and the indiscriminate use of the diverse Bauhinia species is reflected in the experimental divergence of their medicinal potential. Objective: The hypoglycaemic and hypolipidaemic effects, molecular mechanism of action and phytochemical properties of an authentic extract of B. holophylla leaves were evaluated. Materials and methods: A phytochemical study of a 70% EtOH extract was performed using FIA-ESI-IT-MS/MSn and HPLC-PAD-ESI-IT-MS. The extract (200 or 400 mg/kg b.w.) was administered for 14 days to streptozotocin-induced diabetic Swiss mice. Glucose tolerance and insulin sensitivity, blood parameters, gene and protein expression, and the in vivo and in vitro inhibition of intestinal glucosidases were assessed. Results: HPLC-PAD-ESI-IT-MS analysis identified flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol. Treatment with 400 mg/kg of the extract reduced blood glucose (269.0 +/- 32.4 mg/dL vs. 468.0 +/- 32.2 mg/dL for diabetic animals), improved glucose tolerance, decreased cholesterol and triglyceride levels, and increased the mRNA expression of proteins involved in glucogenesis in the liver and muscle, such as PI3-K/Akt, GS, GSK3-beta (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 mu g/mL for the extract compared to 516.4 mu g/mL for acarbose) and in vivo. Discussion and conclusions: Treatment with B. holophylla was associated with a marked hypoglycaemic effect through the stimulation of glycogenesis and inhibition of gluconeogenesis and intestinal glucose absorption, without increasing basal insulinaemia.