Induction of PPAR α and PPAR γ Activity by Plants Extracts

PPAR isoforms (a, g, and d) are members of the nuclear receptor superfamily of ligand-activated transcription factors. In general, PPARa regulates genes involved in fatty acid uptake and oxidation, inflammation and vascular function, whereas PPARg regulates genes involved in fatty acid uptake and storage, inflammation and glucose homeostasis [1]. Synthetic agonists for these receptors are used for treatment of a variety of metabolic abnormalities, including Type II diabetes mellitus and dyslipidemia [2]. PPARs have become important targets to treat human metabolic disorders and in recent years PPAR ligands are emerging as important class of therapeutic agents.

In search of PPAR ligands from natural sources, a collection of 83 Panamanian plants extracts (representing 42 families, 71 genera and 75 species) from the repository of the National Center for Natural Products Research (NCNPR) were screened for their activity on PPARa and PPARg in a cell based reporter gene assay. All extracts were initially tested at a concentration of 100µg/mL. Extracts showing a fold induction of 2 or more in PPAR activity compared to control were considered active and further tested at three concentrations to determine a dose response effect. Based on this primary activity, plants were selected for further study which included the determination of their activity on the expression of PPARs in HepG2 cells by immunoblot analysis, cytotoxicity determination as well as their effects on targets for inflammation. Bioguided fractionation of select plants will be performed to isolate bioactive components. Acknowledgements: Financial support (Yelkaira Vasquez) by Secretaria Nacional de Ciencia y Tecnologia (SENACYT) in collaboration with the Instituto para la Formacion de Recursos Humanos (IFARHU) from the Panamanian government is acknowledged. Partial support of this work from The United States Department of Agriculture, Agricultural Research Service Specific Cooperative Agreement No. 58–6408–2-0009 is also acknowledged. References: [1] Staels B, Fruchart J (2005) Diabetes, Vol. 54, p.2460–2470. [2] Berger J, Akiyama T, Meinke P. (2005) Trends Pharmacol Sci Vol. 26, p.244–251.