The CIHR Team in aboriginal antidiabetic medicines: a community-based collaborative approach uniting healers and biomedical scientists to validate Cree traditional medicine

Obesity and Type 2 diabetes are considered global epidemics by WHO. Aboriginal people such as the Cree of Eeyou Istchee (James Bay area of northern Quebec) are particularly affected and suffer greater complications. This may be due in part to low compliance with modern medicines because of a cultural disconnect. A multidisciplinary team was therefore put together to explore the antidiabetic potential of Cree Traditional Medicine (TM) involving Boreal forest plants. The team is composed equally of scientists with expertise in botany, phytochemistry, nutrition, pharmacology, biochemistry, toxicology and clinical endocrinology, as well as Cree Elders and members of various Cree health institutions, notably including the Cree Board of Health and Social Services of James Bay (CBHSSJB). A novel ethnobotanical approach based on diabetes symptoms was used to identify potential antidiabetic plants, and a total of 17 species were characterized phytochemically. Each species was screened for primary antidiabetic activity using 1) a pancreatic beta cell line to assess effects on glucose-dependent insulin secretion; 2) muscle and adipocytes cell lines to assess effects on insulin-dependent and -independent glucose transport; 3) an adipocyte cell line to assess glitazone-like activity; 4) an intestinal cell line to assess effects on glucose transport. Secondary antidiabetic activity screening included 1) protection against hyper- or hypoglycaemia in a pre-neuronal cell line; 2) pro- or anti-inflammatory activity in a macrophage cell line; 3) anti-oxidant and anti-glycation activity using cell free bioassays. Toxicological potential was also assessed by using an array of recombinant cytochrome P450 isoforms (CYPs) and other flavin-containing oxygenases. No species affected insulin secretion but several plant extracts increased basal and/or insulin-dependent glucose transport in muscle cells, adipocytes or both, while inhibiting intestinal glucose transport and exhibiting weak to moderate inhibition of CYPs. For such promising species, detailed studies uncovered a predominant mode of action related to inhibition of mitochondrial respiration and activation of AMPK, similar to metformin. For several of these species, active principles have been identified using bioassay-guided fractionation. Bioavailibility, antihyperglycemic and/or anti-obesity efficacy has been confirmed for 4 plants using in vivo animal models of obesity, insulin resistance or diabetes. Clinical studies are also underway to document the safety and efficacy of Cree TM using a culturally-adapted, all-inclusive, observational protocol. Finally, our project represents a pilot study for the integration of Cree TM into diabetes care for the CBHSSJB.