Pharmacokinetic, in Vitro and in Silico Assessment of Anti-Inflammatory Alkaloids from Isatis Tinctoria L.

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.