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

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De Paula Camaforte, Nathalia Ap ^[1] ; Saldanha, Luiz Leonardo ^[1] ; Ponce Vareda, Priscilla Maria ^[1] ; Rezende-Neto, Joao M. ^[2] ; Senger, Mario R. ^[2] ; Delgado, Aislan Q. ^[1] ; Morgan, Henrique J. N. ^[3] ; Violato, Natalia Moretti ^[1] ; Pieroni, Lais Goyos ^[1] ; Dokkedal, Anne Ligia ^[3] ; Silva, Floriano P. ^[2] ; Bosqueiro, Jose Roberto ^[4]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Inst Biosci, Botucatu, SP - Brazil

^[2] Oswaldo Cruz Inst FIOCRUZ, Lab Expt & Computat Biochem Drugs, Rio De Janeiro - Brazil

^[3] Sao Paulo State Univ, Dept Biol Sci, Bauru, SP - Brazil

^[4] Sao Paulo State Univ, Dept Phys Educ, Bauru, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Pharmaceutical Biology; v. 57, n. 1, p. 269-279, JAN 1 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 16/18628-4 - Litospermosídeo, um cianoglicosídeo não cianogênico obtido das folhas de Bauhinia holophylla (Bong.) Steud. com potente efeito hipoglicemiante: estudo dos mecanismos de ação hepáticos.
• Beneficiário: José Roberto Bosqueiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/52237-9 - Fitoterápicos padronizados como alvo para o tratamento de doenças crônicas
• Beneficiário: Wagner Vilegas
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 13/10708-0 - Investigação dos mecanismos de ação do extrato bruto de bauhinia holophylla em fígado, músculo esquelético e tecido adiposo em modelo de diabetes tipo 1 induzidos por estreptozotocina.
• Beneficiário: Nathalia Aparecida de Paula Camaforte Henriques
• Modalidade de apoio: Bolsas no Brasil - Doutorado