Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.
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.
Danz
Henning
H
Institute of Pharmacy, University of Jena, Jena, Germany.
Stoyanova
Stefka
S
Thomet
Olivier A R
OA
Simon
Hans-Uwe
HU
Dannhardt
Gerd
G
Ulbrich
Holger
H
Hamburger
Matthias
M
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
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