Pharmacokinetics and in vitro blood-brain barrier screening of the plant-derived alkaloid tryptanthrin

Jähne, E. A. and Eigenmann, D. E. and Sampath, C. and Butterweck, V. and Culot, M. and Cecchelli, R. and Walter, F. R. and Deli, M. A. and Smiesko, M. and Hamburger, M. and Oufir, M.. (2016) Pharmacokinetics and in vitro blood-brain barrier screening of the plant-derived alkaloid tryptanthrin. Planta Medica, 82 (11-12). pp. 1021-1029.

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The indolo[2,1-b]quinazoline alkaloid tryptanthrin was previously identified as a potent anti-inflammatory compound with a unique pharmacological profile. It is a potent inhibitor of cyclooxygenase-2, 5-lipooxygenase-catalyzed leukotriene synthesis, and nitric oxide production catalyzed by the inducible nitric oxide synthase. To characterize the pharmacokinetic properties of tryptanthrin, we performed a pilot in vivo study in male Sprague-Dawley rats (2 mg/kg bw i. v.). Moreover, the ability of tryptanthrin to cross the blood-brain barrier was evaluated in three in vitro human and animal blood-brain barrier models. Bioanalytical UPLC-MS/MS methods used were validated according to current international guidelines. A half-life of 40.63 ± 6.66 min and a clearance of 1.00 ± 0.36 L/h/kg were found in the in vivo pharmacokinetic study. In vitro data obtained with the two primary animal blood-brain barrier models showed a good correlation with an immortalized human monoculture blood-brain barrier model (hBMEC cell line), and were indicative of a high blood-brain barrier permeation potential of tryptanthrin. These findings were corroborated by the in silico prediction of blood-brain barrier penetration. P-glycoprotein interaction of tryptanthrin was assessed by calculation of the efflux ratio in bidirectional permeability assays. An efflux ratio below 2 indicated that tryptanthrin is not subjected to active efflux.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Ehemalige Einheiten Pharmazie > Molecular Modeling (Vedani)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)
UniBasel Contributors:Hamburger, Matthias and Oufir, Mouhssin and Jähne, Evelyn and Eigenmann, Daniela and Smiesko, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Georg Thieme Verlag
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Oct 2017 08:12
Deposited On:30 Oct 2017 08:12

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