Indigenous populations in Canada possess a wealth of native traditional knowledge. However, their rates of Type 2 diabetes mellitus (T2DM), a disease that was unheard of in their midst 50 years ago, are the highest in the country. In an effort to cut the impact of T2DM epidemic on Indigenous health, the Canadian Institutes of Health Research funded the “CIHR Team in Aboriginal Antidiabetic Medicines (CIHR-TAAM).” The goal was to explore Boreal forest medicinal plants stemming from Indigenous Traditional Medicine to be included in T2DM care. Six out of nine communities of the Cree of Eeyou Istchee (CEI) participated in ethnobotanical studies that resulted in the identification of 17 potential antidiabetic plant species. These species were screened for antidiabetic activities using a platform of in vitro bioassays and in vivo models of T2DM. This paper summarizes results on the 10 most promising plant species, their active constituents, and the mechanisms behind their antidiabetic activities. In addition, potential herb-drug interactions were examined at the level of drug-metabolizing enzymes, notably the cytochrome P450 family. This review serves as a canvas onto which is discussed the value of Indigenous medicinal plants, future avenues of research, and the ethical approach required in this field. 1. Introduction Over the past decades, the world has witnessed a noticeable surge in the number of diabetes mellitus (DM) cases. According to International diabetes federation (IDF), the disease continues to tighten its grip. By 2035, one person out of ten will be diabetic. Every year, DM causes the death of 5.1 million people. In addition, more than a million lower limb amputations, half a million kidney failures, and 1.5 million cases of blindness occur annually as long-term diabetic complications [1]. The two most common forms of DM are type 1 DM (T1DM) and type 2 DM (T2DM). The latter is diagnosed by increased fasting glycemia (≥7？mM), elevated postprandial glycemia (≥11？mM), and an augmented hemoglobin A1C (≥6.5%) [2]. While T1DM is still rare in Indigenous populations worldwide, they endure disproportionately high rates of T2DM. Indigenous populations of Canada are not exceptions to this rule; the age-standardized rates of T2DM among them being several fold higher than the rest of the country (17.2% versus 5%, resp.) [3]. In general, Indigenous individuals are diagnosed with T2DM at a younger age and Indigenous women have higher rates of gestational diabetes. Finally, considering that obesity is closely associated with T2DM, Indigenous communities have
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