Planta Med 2011; 77 - PL36
DOI: 10.1055/s-0031-1282685

Discovery of new indoleamine-2,3-dioxygenase inhibitors from Carthamus tinctorius

S Kuehnl 1, S Schroecksnadel 2, JM Rollinger 1, D Fuchs 2, H Stuppner 1
  • 1Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences, University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria
  • 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz-Pregl-Straße 3, 6020 Innsbruck, Austria

Indoleamin-2,3-dioxygenase (IDO) is the rate limiting step of tryptophan catabolism. As its expression is induced by Type II interferone (INF-γ), it is involved in inflammatory diseases [1]. In neurological disorders, degradation of tryptophan can reduce serotonin synthesis, which is related to major depression [2]. Furthermore, quinolinic acid originating from tryptophan catabolism has neurotoxic effects. In cancer cells, the expression of IDO leads to a local suppression of T-cell responses and promotes immune tolerance. Therefore, IDO is an interesting target for therapeutic intervention in these conditions [1]. As Carthamus tinctorius L. was used in ethnopharmacology against inflammatory diseases and also against cancer [3] and depression [4], this plant was investigated for IDO inhibitors. Three lignans isolated from Carthamus tinctorius seed oil cake were tested for inhibition of IDO in peripheral blood mononuclear cells (PBMCs), namely arctigenin, trachelogenin and matairesinol. Arctigenin and trachelogenin inhibited IDO with IC50 of 26.49 and 57.35µM whereas matairesinol showed only slight activity.

Acknowledgement: This work was supported by the TWF („Tiroler Zukunftsstiftung“) and the Austrian Science Fund (FWF; S10703).

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