Isomeric C12-alkamides from the roots of Echinacea purpurea improve basal and insulin-dependent glucose uptake in 3T3-L1 adipocytes

Planta Med. 2014 Dec;80(18):1712-20. doi: 10.1055/s-0034-1383252. Epub 2014 Nov 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells / drug effects
  • Animals
  • Biological Transport / drug effects
  • Dose-Response Relationship, Drug
  • Echinacea / chemistry*
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin / pharmacology
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry
  • Plant Roots / metabolism
  • Plants, Medicinal / chemistry
  • Polyunsaturated Alkamides / chemistry
  • Polyunsaturated Alkamides / pharmacology*

Substances

  • Hypoglycemic Agents
  • Insulin
  • PPAR gamma
  • Plant Extracts
  • Polyunsaturated Alkamides
  • Glucose