Treatment of obesity and diabetes by a Canadian aboriginal medicinal plant in a mouse model of diet-induced type 2 diabetes

The prevalence of the metabolic syndrome is increasing among the Cree of Eeyou Istchee (CEI - Northern Quebec) as a result of increases in obesity and insulin resistance. Non-traditional diet and sedentary lifestyle along with cultural disconnect of modern type 2 diabetes (T2D) therapies are involved. Exploring treatments from within CEI traditional pharmacopeia represents a valuable alternative. W7, a CEI plant extract from the Canadian Boreal Forest, demonstrated antiobesity and anti-diabetic properties in a recent in-vivo prevention study. We thus evaluated the potential effects of two preparations (aqueous (AE) and ethanolic (EE) extracts) of this plant in a mouse model of diet-induced obesity and T2D. C57/BL6 mice were subjected to high fat (HF) diet for sixteen weeks resulting in obesity, hyperinsulinemia and mild steady-state hyperglycemia. Plant extracts were introduced in the HF diet for the last eight weeks and tested at doses of 125 and 250 mg/Kg as the in-vivo prevention study. Treatment with EE 125 was found to have the most significant effects. It significantly decreased body weight by 13% and retroperitoneal fat pad weight by 16% as compared to HF control mice. No statistical difference was observed in water or food intake. In EE 125 animals, plasma insulin was significantly diminished by 87 % compared to HF controls. Area under the curve of glycemia versus time was also reduced in treated animals and statistical significance was reached in the EE 250 group (15% reduction) as was the ratio of insulinemia to glycemia (64 % by EE 250 and 85% by EE 125). The effectiveness of EE 125 was also related to a decrease in the lipid content of the liver, as confirmed by histological analysis revealing a significant reduction in the proportion of steatotic livers and a shift toward more moderate grades of steatosis as compared to HF controls. The relative liver weight was significantly reduced by 20 % by EE compared to HF controls. Moreover, treatment of animals by EE 125 significantly diminished plasma leptin by 41 % and leptin/adiponectin ratio by 42 % compared to controls. Plasma TNF-a increased by 800 % in HF controls and was returned to normal values by treatment with each plant extract (AE and EE). The treatment of animals with AE 125 demonstrated a profile of effects similar to EE125 but lower effectiveness. These plant extracts thus exhibit promising anti-obesity and consequently anti-diabetic effects. Mechanisms remain to be elucidated but current results point towards a stimulation of metabolic rate.