Characterization of alkamide isomers as potential partial PPARγ agonists from the roots of purple coneflower

Partial PPARγ agonists are believed not to promote the same magnitude of undesirable side effects as the insulin sensitizing drugs prescribed for the treatment of insulin resistance e.g. thiazolidinediones. Recent investigations of a n-hexane extract of the flowers of purple coneflower (Echinacea purpurea) led to the isolation of a new C₁₆-alkamide able to activate PPARγ with no concurrent stimulation of adipocyte differentiation, and the ability to increase insulin-stimulated glucose uptake in adipocytes [1]. In our search for further bioactive alkamides, the dichloromethane extract of the roots of E. purpurea, previously found to contain potential partial PPARγ agonists, was investigated. A bioassay-guided fractionation, based on insulin-stimulated glucose uptake of the extract, by flash CC and semi-prep HPLC yielded the known isomeric dodeca-2E,4E,8Z,10E/Z-tetraenoic acid 2-methylbutylamides that showed PPARγ activity in a dose-dependent manner from 1 to 8µg/mL. Due to these promising results, testing of these alkamide isomers is in progress in insulin-stimulated glucose uptake and adipocyte differentiation bioassays. Other alkamides from the active fractions warrant further investigation for their bioactive properties.

References: 1. Christensen KB et al. J. Nat. Prod. 2009; 72: 933–937.