Type II diabetes is a major health problem worldwide. Some populations, such as aboriginal peoples, are particularly at risk for this disease. In the Cree Nation of Quebec, Canada, prevalence in adults is approaching 20%, and the consequences are compounded by low compliance with modern medicine. In 2003, we conducted an ethnobotanical study of Cree medicinal plants used for the treatment of symptoms of diabetes. This served as the basis for a project designed to identify efficacious complementary treatment options more readily accepted by this population. The present study assesses the in vitro anti-diabetic potential of extracts from the 8 most promising plants to emerge from the ethnobotanical study. Cell-based bioassays were employed to screen for (i) potentiation of glucose uptake by skeletal muscle cells (C2C12) and adipocytes (3T3-L1); (ii) potentiation of glucose-stimulated insulin secretion (GSIS) and insulin production by pancreatic beta cells (INS 832/13); (iii) potentiation of triglyceride accumulation in differentiating 3T3-L1 cells; (iv) protection against glucose toxicity and glucose deprivation in pre-sympathetic neurons (PC12-AC). Additionally, anti-oxidant activity was measured biochemically by the diphenylpicrylhydrazyl (DPPH) reduction assay. All plant extracts potentiated basal or insulin-stimulated glucose uptake to some degree in muscle cells or adipocytes. Adipocyte differentiation was accelerated by 4 extracts. Five extracts conferred protection in PC12 cells. Three extracts displayed free radical scavenging activity similar to known anti-oxidants. None of the plant extracts enhanced GSIS or insulin content in INS 832/13 beta cells. It is concluded that the Cree pharmacopoeia contains several plants with significant anti-diabetic potential.

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The incidence of type 2 diabetes mellitus has reached epidemic proportions worldwide. Canadian aboriginal communities, particularly the Cree Nation of Eeyou Istchee, have been identified as a high-risk population. Culturally acceptable treatment options are limited notably for diabetic complications resulting in peripheral neuropathy. Here, we describe results of an ongoing collaborative research project with Cree of Eeyou Istchee to identify botanicals capable of protecting peripheral neuronal precursors from glucose toxicity and glucose deprivation in vitro. Polar fractions of three plant organs (needles, cone, and bark) collected from Picea glauca (Moench) Voss (Pinaceae), were tested for toxicity under normoglucose, glucotoxicity, and glucose deprivation conditions. The profile of phenolic metabolites in each extract was first characterized by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionisation mass spectrometry (HPLC-DAD-APCI/MS). We report here that these fractions are well-tolerated by PC12 neuronal precursors under normoglucose conditions. LD 50 concentrations of needle extracts exceeded 100 µg/mL, whereas the LD 50 of bark and cone extracts was 40 and 36.4 µg/mL, respectively. We further show that the cytoprotective properties of minhikw after glucose challenge are concentration-dependent and organ-specific. Needle * Dedicated to John Thor Arnason of the University of Ottawa, Department of Biology, on the occasion of his sixtieth birthday. extracts protected PC12 cells from both glucotoxicity and glucose deprivation. Bark extracts had negligible activity. Cone extracts further impaired PC12 cell glucose tolerance. This study provides the first validation of antidiabetic activity of minhikw organs at the cellular level relevant to the management of diabetic peripheral neuropathy.

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