Planta Med 2011; 77 - PM186
DOI: 10.1055/s-0031-1282944

Polyacetylenes from Notopterygium incisum as a novel class of specific PPARgamma activators

M Blunder 1, N Fakhrudin 2, X Liu 1, O Kunert 3, AG Atanasov 2, VM Dirsch 2, R Bauer 1
  • 1Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-Universität Graz, 8010 Graz, Austria
  • 2Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria
  • 3Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Karl-Franzens-Universität Graz, 8010 Graz, Austria

In the course of our search for PPARγ active anti-inflammatory natural products we have investigated the dichloromethane extract of the dried rhizome and root of Notopterygium incisum Ting ex H. T. Chang (Umbelliferae). PPARγ is one of the three Peroxisome Proliferator Activated Receptor (PPAR) subtypes and is involved in the regulation of glucose and lipid metabolism and therefore an important target for metabolic diseases. Additionally, PPARγ plays a role in other chronic diseases such as inflammation, cancer and atherosclerosis.1 We have isolated six polyacetylenes, which were structurally characterized by means of multidimensional NMR and mass spectroscopy, and which were shown to inhibit NO production in RAW 264.7 macrophages.2 Now, the potency of these polyacetylenes as PPARγ agonists has been evaluated. The EC50s of 8-acetoxyfalcarinol, falcarindiol, 9-epoxy-falcarindiol, crithmumdiol, 9-heptadecene-4,6-diyn-1-ol and 2Z,9Z)-2,9-heptadecadiene-4,6-diyn-1-ol were determined as 2.36-fold activation (EC50 of 3.59µM), 2.29-fold activation (EC50 of 4.25µM), 1.88-fold activation (EC50 of 2.03µM) and 2.29-fold activation (EC50 of 4.58µM), 1.921 fold activation (EC50 of 11.31µM) and 1.73-fold activation (EC50 of 4.18µM), respectively, whereas the positive control pioglitazone exhibited 7.96-fold activation (EC50 of 0.31µM). Therefore, these polyacetylene derivatives contribute to the anti-inflammatory activity of Notopterygium incisum by selectively activating PPARγ without affecting the other two PPAR subtypes.3

Figure 1: Chemical structures of the polyacetylenes from N. incisum.

Keywords: Notopterygium incisum, polyacetylenes, PPARγ, metabolic diseases, PPAR gamma activators

Acknowledgement: We gratefully acknowledge the funding provided by the Austrian Science Fund (FWF) within project NFN S 10705-B13.

References: 1. Schmidt MV et al. (2010) Scientific World Journal 10: 2181–97.

2. Blunder M et al. (2011) Planta Med, in preparation

3. Blunder M et al. (2011)J Nat Prod, in preparation