title: Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase.
abstract: Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of C. tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells in vitro methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of C. tinctorius 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 26.5μM) and trachelogenin (IC50 of 57.4μM) showed higher activity than matairesinol (IC50 >200μM) 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 in vitro results support the view that some of the anti-inflammatory, anticancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown.
authors.affiliation: University of Innsbruck, Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), 6020 Innsbruck, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kuehnl
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schroecksnadel
authors.forename: Veronika
authors.initials: V
authors.lastname: Temml
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gostner
authors.forename: Harald
authors.initials: H
authors.lastname: Schennach
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D031187:Carthamus tinctorius / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D019798:Neopterin / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012639:Seeds / Q000737:chemistry; D014364:Tryptophan / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005663:Furans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017705:Lignans; D010936:Plant Extracts; C560586:trachelogenin; C068935:matairesinol; D019798:Neopterin; D014364:Tryptophan; D015107:4-Butyrolactone; C071942:arctigenin
keywords: Asteraceae; Carthamus tinctorius; Indoleamine 2,3-Dioxygenase; Neopterin; Safflower