Isomeric C12-alkamides from the roots of Echinacea purpurea improve basal and insulin-dependent glucose uptake in 3T3-L1 adipocytes.
Echinacea purpurea has been used in traditional medicine as a remedy for the treatment and prevention of upper respiratory tract infections and the common cold. Recent investigations have indicated that E. purpurea also has an effect on insulin resistance. A dichloromethane extract of E. purpurea roots was found to enhance glucose uptake in adipocytes and to activate peroxisome proliferator-activated receptor γ. The purpose of the present study was to identify the bioactive compounds responsible for the potential antidiabetic effect of the dichloromethane extract using a bioassay-guided fractionation approach. Basal and insulin-dependent glucose uptake in 3T3-L1 adipocytes were used to assess the bioactivity of extract, fractions and isolated metabolites. A peroxisome proliferator-activated receptor γ transactivation assay was used to determine the peroxisome proliferator-activated receptor γ activating properties of the extract, active fractions and isolated metabolites. Two novel isomeric dodeca-2E,4E,8Z,10E/Z-tetraenoic acid 2-methylbutylamides together with two known C12-alkamides and α-linolenic acid were isolated from the active fractions. The isomeric C12-alkamides were found to activate peroxisome proliferator-activated receptor γ, to increase basal and insulin-dependent glucose uptake in adipocytes in a dose-dependent manner, and to exhibit characteristics of a peroxisome proliferator-activated receptor γ partial agonist.
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Dorota
D
Kotowska
Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
Rime B
RB
El-Houri
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Kamil
K
Borkowski
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Rasmus K
RK
Petersen
Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
Xavier C
XC
Fretté
Computer-Aided Drug Design, Institute of Pharmacy, Medicinal and Pharmaceutical Chemistry, Freie Universität Berlin, Berlin, Germany.
Gerhard
G
Wolber
Department of Food Science, Aarhus University, Aarslev, Denmark.
Kai
K
Grevsen
Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
Kathrine B
KB
Christensen
Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark.
Lars P
LP
Christensen
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Karsten
K
Kristiansen
D041721:3T3-L1 Cells / Q000187:drug effects; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020900:Echinacea / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D005947:Glucose