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Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase
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Seed extracts of m>Carthamus tinctoriusm> L. (m>Asteraceaem>), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of m>C. tinctoriusm> compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of m>C. tinctoriusm> extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells m>in vitrom> methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of m>C. tinctoriusm> and three lignan derivatives, trachelogenin, arctigenin and matairesinol were isolated. The influence on tryptophan breakdown was investigated in peripheral blood mononuclear cells (PBMCs). Effects were compared to neopterin production in the same cellular assay. Both seed extracts suppressed tryptophan breakdown in stimulated PBMC. The three structurally closely related isolates exerted differing suppressive activity on PBMC: arctigenin (IC50 26.5 ¦ÌM) and trachelogenin (IC50 of 57.4 ¦ÌM) showed higher activity than matairesinol (IC50 >200 ¦ÌM) to inhibit tryptophan breakdown. Effects on neopterin production were similar albeit generally less strong. Data show an immunosuppressive property of compounds which slows down IDO activity. The m>in vitrom> results support the view that some of the anti-inflammatory, anticancer and antidepressant properties of m>C. tinctoriusm> lignans might relate to their suppressive influence on tryptophan breakdown.

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