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 B₂ (TxB₂) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F_{1 α} (6-keto-PGF_{1 α}) 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 B₄ (LTB₄) 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 LTB₄ release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

Key words

Tryptanthrin - Isatis tinctoria - Brassicaceae - HEL cells - Mono Mac 6 cells - RAW 264.7 - thrombocytes - BAECs - granulocytes - cyclooxygenase-2 - cyclooxygenase-1 - 5-lipoxygenase - 6-keto-PGF_{1 a} - TxB₂ - LTB₄

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