title: Adipogenic constituents from the bark of Larix laricina du Roi (K. Koch; Pinaceae), an important medicinal plant used traditionally by the Cree of Eeyou Istchee (Quebec, Canada) for the treatment of type 2 diabetes symptoms.
abstract: BACKGROUND
  Diabetes is a growing epidemic worldwide, especially among indigenous populations. Larix laricina was identified through an ethnobotanical survey as a traditional medicine used by Healers and Elders of the Cree of Eeyou Istchee of northern Quebec to treat symptoms of diabetes and subsequent in vitro screening confirmed its potential.
  
  
  METHODS
  We used a bioassay-guided fractionation approach to isolate the active principles responsible for the adipogenic activity of the organic extract (80% EtOH) of the bark of Larix laricina. Post-confluent 3T3-L1 cells were differentiated in the presence or absence of the crude extract, fractions or isolates of Larix laricina for 7 days, then triglycerides content was measured using AdipoRed reagent.
  
  
  RESULTS
  We identified a new cycloartane triterpene (compound 1), which strongly enhanced adipogenesis in 3T3-L1 cells with an EC(50) of 7.7 μM. It is responsible for two thirds of the activity of the active fraction of Larix laricina. The structure of compound 1 was established on the basis of spectroscopic methods (IR, HREIMS, 1D and 2D NMR) as 23-oxo-3α-hydroxycycloart-24-en-26-oic acid. We also identified several known compounds, including three labdane-type diterpenes (compounds 2-4), two tetrahydrofuran-type lignans (compounds 5-6), three stilbenes (compounds 7-9), and taxifolin (compound 10). Compound 2 (13-epitorulosol) also potentiated adipogenesis (EC(50) 8.2 μM) and this is the first report of a biological activity for this compound.
  
  
  CONCLUSIONS
  This is the first report of putative antidiabetic principles isolated from Larix laricina, therefore increasing the interest in medicinal plants from the Cree pharmacopeia.
authors.affiliation: Natural Health Products and Metabolic Disease Laboratory, Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
authors.forename: Nan
authors.initials: N
authors.lastname: Shang
authors.forename: José A
authors.initials: JA
authors.lastname: Guerrero-Analco
authors.forename: Lina
authors.initials: L
authors.lastname: Musallam
authors.forename: Ammar
authors.initials: A
authors.lastname: Saleem
authors.forename: Asim
authors.initials: A
authors.lastname: Muhammad
authors.forename: Brendan
authors.initials: B
authors.lastname: Walshe-Roussel
authors.forename: Alain
authors.initials: A
authors.lastname: Cuerrier
authors.forename: John T
authors.initials: JT
authors.lastname: Arnason
authors.forename: Pierre S
authors.initials: PS
authors.lastname: Haddad
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000032:analysis / Q000494:pharmacology*; D007198:Indians, North American; D028221:Larix; D008519:Medicine, Traditional; D051379:Mice; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D010946:Plants, Medicinal; D011792:Quebec; D014315:Triterpenes / Q000032:analysis / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D010936:Plant Extracts; D014315:Triterpenes