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 (Article)

PLoS ONE

Volume 10, Issue 8, 11 August 2015, Article number e0135721

Shang, N.^abc, 

Saleem, A.^bd, 

Musallam, L.^ab, 

Walshe-Roussel, B.^bd, 

Badawi, A.^e, 

Cuerrier, A.^bf, 

Arnason, J.T.^bd, 

Haddad, P.S.^abc 

^a  Natural Health Products and Metabolic Disease Laboratory and Montreal Diabetes Research Center, Department of Pharmacology, Université de Montréal, Montreal, QC, Canada
^b  Canadian Institutes of Health Research Team, Aboriginal Antidiabetic Medicines, Montreal, QC, Canada
^c  Institute of Nutraceuticals and Functional Foods, Université Laval, Quebec, QC, Canada

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Abstract

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. Copyright: © 2015 Shang et al.

Indexed keywords

EMTREE drug terms: Abies balsamea extract; alcohol; Alnus incana extract; flavone derivative; Gaultheria hispidula extract; glucose; glucose 6 phosphatase; glucose transporter 4; hot water; hydroxymethylglutaryl coenzyme A reductase kinase; hyperin; insulin; Juniperus communis extract; Kalmia angustifolia extract; Larix laricina extract; Lycopodium clavatum extract; Picea glauca extract; Picea mariana extract; Pinus banksiana extract; plant extract; Populus balsamifera extract; quercetin 3 o alpha arabinopyranoside; Rhododendron groenlandicum extract; Rhododendron tomentosum extract; Salix planifolia extract; Sarracenia purpurea extract; Sorbus decora extract; unclassified drug; Vaccinium vitis idaea extract

EMTREE medical terms: Abies balsamea; alder; Alnus incana; animal cell; antidiabetic activity; Article; bioassay; black spruce; C2C12 cell line; Canada; controlled study; drug determination; drug mechanism; enzyme activation; enzyme activity; ethnobotany; fractionation; Gaultheria; Gaultheria hispidula; glucose homeostasis; glucose transport; hepatoma cell; in vitro study; insulin metabolism; Juniperus; Kalmia angustifolia; Larix; Larix laricina; lingonberry; Lycopodium; medicinal plant; metabolomics; muscle cell; nonhuman; phytochemistry; pine; Pinus banksiana; Populus balsamifera; protein analysis; protein expression; rat; Rhododendron; Rhododendron groenlandicum; Rhododendron tomentosum; Salix planifolia; Sarracenia purpurea; signal transduction; Sorbus; Sorbus decora; white spruce; willow

Chemicals and CAS Registry Numbers: alcohol, 64-17-5; glucose, 50-99-7, 84778-64-3; glucose 6 phosphatase, 9001-39-2; glucose transporter 4, 188071-24-1; hydroxymethylglutaryl coenzyme A reductase kinase, 172522-01-9, 72060-32-3; hyperin, 482-36-0; insulin, 9004-10-8

ISSN: 19326203 CODEN: POLNCSource Type: Journal Original language: English

DOI: 10.1371/journal.pone.0135721Document Type: Article

Publisher: Public Library of Science

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