Pharmacokinetic, in vitro and in silico assessment of anti-inflammatory alkaloids from Isatis tinctoria L.

Abstract

We previously identified the alkaloids tryptanthrin (1), indirubin (2) and indolinone (3) as pharmacologically active compounds in woad (Isatis tinctoria L.). They inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations, and they possess drug-like physico-chemical properties. A pilot pharmacokinetic study in rats (2 mg/kg i.v. b.w.) showed that 1 and 2 have half-lives of 30 – 40 min, whereas 3 was rapidly eliminated. In silico predictions for 1 – 3 indicated high oral absorption and favourable blood-brain transport. In animal and human in vitro blood-brain-barrier (BBB) models 1 and 3 displayed high BBB permeation. In the Caco-2 intestinal absorption model, 1 showed high permeation, while the recovery of 3 was low.