The liver plays an essential role in the regulation of glucose homeostasis and in the pathogenesis of type 2 diabetes mellitus. This study sought to determine the potential beneficial effect of putative antidiabetic medicinal plants used by the Eastern James Bay Cree of Northern Quebec (Canada) on the activity of key enzymes of gluconeogenesis and glycogen synthesis. Glucose-6-phosphatase (G6Pase) activity was measured by glucose oxidase enzymatic assay and glycogen synthase (GS) activity was assessed by the amount of radioactive UDP-glucose incorporated into glycogen in hepatic cell lines. The phosphorylation of AMP-dependent protein kinase (AMPK) and Glycogen synthase kinase-3 (GSK-3), the two key kinases that control the two pathways for glucose homeostasis, were probed by Western blot. Eight of the seventeen tested plant extracts significantly inhibited G6Pase, the key enzyme for gluconeogenesis, and activated glycogen synthase, the enzyme responsible for storage of glucose as glycogen. Phosphorylation of AMPK and GSK-3 were increased significantly by several active extracts. The most active extract showed 48% of inhibition for G-6Pase and over 10-fold activation of GS. Bioassay guided fractionation of this extract identified the hexane fraction as the most active (50% inhibition of G6Pase; very high activation of GS). The subfractionation of the hexane fraction yielded eight pure compounds, three of which are active. Several Cree antidiabetic medicinal plants modulate G6Pase and GS. The crude extract and the pure compounds of the most active species have potential to treat type 2 diabetes.
