Novel Approach to Identify Potential Bioactive Plant Metabolites: Pharmacological and Metabolomics Analyses of Ethanol and Hot Water Extracts of Several Canadian Medicinal Plants of the Cree of Eeyou Istchee.
We evaluated and compared the antidiabetic potential and molecular mechanisms of 17 Cree plants' ethanol extracts (EE) and hot water extracts (HWE) on glucose homeostasis in vitro and used metabolomics to seek links with the content of specific phytochemicals. Several EE of medical plants stimulated muscle glucose uptake and inhibited hepatic G6Pase activity. Some HWE partially or completely lost these antidiabetic activities in comparison to EE. Only R. groenlandicum retained similar potential between EE and HWE in both assays. In C2C12 muscle cells, EE of R. groenlandicum, A. incana and S. purpurea stimulated glucose uptake by activating AMP-activated protein kinase (AMPK) pathway and increasing glucose transporter type 4 (GLUT4) expression. In comparison to EE, HWE of R. groenlandicum exhibited similar activities; HWE of A. incana completely lost its effect on all parameters; interestingly, HWE of S. purpurea activated insulin pathway instead of AMPK pathway to increase glucose uptake. In the liver, for a subset of 5 plants, HWE and EE activated AMPK pathway whereas the EE and HWE of S. purpurea and K. angustifolia also activated insulin pathways. Quercetin-3-O-galactoside and quercetin 3-O-α-L-arabinopyranoside, were successfully identified by discriminant analysis as biomarkers of HWE plant extracts that stimulate glucose uptake in vitro. More importantly, the latter compound was not identified by previous bioassay-guided fractionation.
Natural Health Products and Metabolic Disease Laboratory and Montreal Diabetes Research Center, Department of pharmacology, Université de Montréal, Montreal, Quebec, Canada; Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada; Institute of Nutraceuticals and Functional Foods, Université Laval, Quebec, Quebec, Canada.
Nan
N
Shang
Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada; Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada.
Ammar
A
Saleem
Natural Health Products and Metabolic Disease Laboratory and Montreal Diabetes Research Center, Department of pharmacology, Université de Montréal, Montreal, Quebec, Canada; Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada.
Lina
L
Musallam
Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada; Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada.
Brendan
B
Walshe-Roussel
Office for Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, Ontario, Canada.
Alaa
A
Badawi
Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada; Jardin botanique de Montréal, Institut de recherche en biologie végétale, Université de Montréal, Montréal, Quebec, Canada.
Alain
A
Cuerrier
Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada; Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada.
John T
JT
Arnason
Natural Health Products and Metabolic Disease Laboratory and Montreal Diabetes Research Center, Department of pharmacology, Université de Montréal, Montreal, Quebec, Canada; Canadian Institutes of Health Research Team in Aboriginal Antidiabetic Medicines, Montreal, Quebec, Canada; Institute of Nutraceuticals and Functional Foods, Université Laval, Quebec, Quebec, Canada.
Pierre S
PS
Haddad
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002170:Canada; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D051275:Glucose Transporter Type 4; D007328:Insulin; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005952:Glucose-6-Phosphatase; D005947:Glucose