title: Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.
abstract: The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.
authors.affiliation: Institute of Pharmacy, University of Jena, Jena, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Danz
authors.forename: Stefka
authors.initials: S
authors.lastname: Stoyanova
authors.forename: Olivier A R
authors.initials: OA
authors.lastname: Thomet
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
authors.forename: Gerd
authors.initials: G
authors.lastname: Dannhardt
authors.forename: Holger
authors.initials: H
authors.lastname: Ulbrich
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D000818:Animals; D019607:Brassicaceae; D002478:Cells, Cultured / Q000187:drug effects; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000096:biosynthesis*; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010936:Plant Extracts; D011453:Prostaglandins; D011799:Quinazolines; C046243:tryptanthrine; D007975:Leukotriene B4; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases