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

羊蹄甲通过抑制GSK3-β和激活糖原生成发挥降血糖作用

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作者:Nathalia Ap De Paula Camaforte, Luiz Leonardo Saldanha, Priscilla Maria Ponce Vareda, João M Rezende-Neto, Mario R Senger, Aislan Q Delgado, Henrique J N Morgan, Natalia Moretti Violato, Laís Goyos Pieroni, Anne Lígia Dokkedal, Floriano P Silva-Júnior, José Roberto Bosqueiro

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.

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.

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

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-β (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 µg/mL for the extract compared to 516.4 µg/mL for acarbose) and in vivo.

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