Planta Med 2011; 77 - WSII2
DOI: 10.1055/s-0031-1282101

New cerebrosides and hydroxylated fatty acids from TCM drugs

E Rozema 1, R Popescu 1, H Sonderegger 2, C Uhlschmied 2, N Fakhrudin 1, G Reznicek 1, AG Atanasov 1, EH Heiss 1, GK Bonn 2, D Schuster 3, E Urban 4, CW Huck 2, VM Dirsch 1, B Kopp 1
  • 1Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria
  • 2Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innrain 52a, 6020 Innsbruck, Austria
  • 3Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria
  • 4Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria

In recent years, increasing attention has been drawn towards the role of lipids in cell signalling pathways and regulation.(1) Plants are a rich source of bioactive lipids. We, therefore, focused on (complex) lipids from plants used as traditional Chinese medicinal (TCM) drugs and their influence on cellular processes. Four new cerebrosides, which belong to the compound class of sphingolipids, were isolated and characterized from Arisaema amurense and Pinellia ternata (Araceae).(2) Structure elucidation was performed by NMR and mass spectrometry. The compounds were screened for cytotoxicity against cells of 6 different cancer and non-cancerous cell-lines. While the cerebrosides lacked cytotoxic activity, the breakdown product 4,8-sphingadienine showed cytotoxic effect in two types of leukemic cell lines with IC50 >20µM. The effect, however, was similar also in non-cancerous cells (IC50 >20µM). Common fatty acids were found in A. amurense, P. ternata and Albizia julibrissin (Fabaceae). The fatty acids showed high PPARα and -γ activation in a PPAR-luciferase reporter gene assay. Beside these known PPAR ligands, hydroxylated fatty acids, derived from linoleic acid via the lipoxygenase pathway, were isolated from A. julibrissin.(2) The influence of the hydroxyl-group(s) on binding to the ligand binding domain (LBD) of PPARγ was studied in silico using the program LigandScout.(3) A pharmacophore model was generated based on available complexes of hydroxylated fatty acids with the PPARγ LBD. Thereby, part of the isolated trihydroxylated fatty acids and hydroxy-epoxy fatty acids were predicted to bind to the PPARγ LBD.

Keywords: cerebrosides, hydroxylated fatty acids, TCM

Acknowledgement: This project was supported by the Sino-Austria Project [FF55–2004] from the Austrian Federal Ministry and in part by the Austrian Science Fund [NFN S10704-B037 and NFN S10702-B03].

References: 1. Evans JF, Hutchinson JH (2010) Nat Chem Biol 6: 476–9. 2. Bensky D et al (2004) Chinese Herbal Medicine, Materia Medica. Eastland Press. Seattle. 3. Wolber G, Langer T (2005)J Chem Inf Model 45:160–9.