Bioassay-guided purification and identification of PPARα/γ agonists fromChlorella sorokiniana

This study isolated agonists of peroxisome proliferator activated receptors (PPARs) from the green algae Chlorella sorokiniana, using a bioassay-guided purification strategy. PPARs are widely recognized as the molecular drug targets for many diseases including hyperglycemia, diabetes, obesity and cancer. Two independent bioassays were developed. The first is the scintillation proximity assay, a ligand binding assay. The other is the cell-based transcriptional activation assay which uses the Dual-Luciferase (R) reporter system as the reporter gene under the control of the PPAR response element. Using these two assays, a PPAR gamma-active fraction, CE 3-3, was obtained from C. sorokiniana extracts, which was also able to activate PPAR alpha-mediated gene expression. To elucidate the active ingredients in the CE 3-3 fraction, GC-MS analysis was employed. The results showed that the CE 3-3 fraction consisted of at least ten fatty acids (FAs). The bioactivities of several of the individual FAs were evaluated for their PPAR gamma activity and the results showed that linolenic acid and linoleic acid were the most potent FAs tested. Our studies indicate that Chlorella sorokiniana could have potential health benefits through the dual activation of PPAR alpha/gamma via its unique FA constituents. Copyright (C) 2008 John Wiley & Sons, Ltd.