Metabolites from purple coneflower (Echinacea purpurea) identified as PPARγ agonists

One of the major characteristics of Type 2 Diabetes is insulin resistance, which is often treated by insulin sensitizing drugs such as thiazolidinediones (TZDs). The primary target for the TZDs is the peroxisome proliferator-activated receptor (PPAR) γ. However, critical side effects of TZDs can occur, as they are full PPARγ agonists. Partial PPARγ agonists are associated with fewer side effects but still may maintain the effect on insulin resistance. Recently, a general screening for potential partial PPARγ agonists was carried out on a number of plant extracts. This screening resulted in a 60% hit rate among the tested plant species and one of the most promising of these was purple coneflower (Echinacea purpurea) [1]. Based on this general screening a large-scale bioassay-guided fractionation of a hexane extract of the flowers of purple coneflower was carried out. The fractionations were done by flash column chromatography and reverse phase semi-preparative HPLC for isolation of active constituents. Bioactivity of fractions and purified compounds were assessed using a PPARγ transactivation assay. Mouse embryonic fibroblasts were used for this assay and each sample was tested in triplicate in three different concentrations. Activation of PPARγ for each sample was compared to both vehicle (DMSO) and the TZD rosiglitazone, as a positive control. Two of the compounds being able to activate PPARγ were isolated and identified as linoleic acid and linolenic acid, but also some of the isolated alkamides were shown to activate PPARγ. Hence, the PPARγ activating properties of purple coneflower also seem to depend on the presence of these specific alkamides. This suggest a whole new field of application for purple coneflower which is one of the most extensively used medicinal plants worldwide for treatment of the common cold.

References: 1. Christensen, K.B. et al. 2008, unpublished.