Planta Med 2014; 80(18): 1712-1720
DOI: 10.1055/s-0034-1383252
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Isomeric C12-Alkamides from the Roots of Echinacea purpurea Improve Basal and Insulin-Dependent Glucose Uptake in 3T3-L1 Adipocytes

Dorota Kotowska*
1  Department of Biology, University of Copenhagen, Copenhagen, Denmark
,
Rime B. El-Houri*
2  Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark
,
Kamil Borkowski
1  Department of Biology, University of Copenhagen, Copenhagen, Denmark
,
Rasmus K. Petersen
1  Department of Biology, University of Copenhagen, Copenhagen, Denmark
,
Xavier C. Fretté
2  Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark
,
Gerhard Wolber
3  Computer-Aided Drug Design, Institute of Pharmacy, Medicinal and Pharmaceutical Chemistry, Freie Universität Berlin, Berlin, Germany
,
Kai Grevsen
4  Department of Food Science, Aarhus University, Aarslev, Denmark
,
Kathrine B. Christensen
2  Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark
,
Lars P. Christensen
2  Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark
,
Karsten Kristiansen
1  Department of Biology, University of Copenhagen, Copenhagen, Denmark
› Author Affiliations
Further Information

Publication History

received 24 June 2014
revised 23 August 2014

accepted 12 October 2014

Publication Date:
05 November 2014 (online)

Abstract

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.

* Dorota Kotowska and Rime B. El-Houri contributed equally to the work.


Supporting Information