Pharmacokinetics and in Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin

Evelyn A. Jähne, Daniela E. Eigenmann, Chethan Sampath, Veronika Butterweck, Maxime Culot, Roméo Cecchelli, Fabien Gosselet, Fruzsina R. Walter, M. Deli, Martin Smieško, Matthias Hamburger, Mouhssin Oufir

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1021-1029
Number of pages9
JournalPlanta Medica
Volume82
Issue number11-12
DOIs
Publication statusPublished - Jul 1 2016

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Pharmacokinetics
Blood-Brain Barrier
Alkaloids
Screening
Animals
Leukotrienes
Cyclooxygenase 2 Inhibitors
P-Glycoprotein
Nitric Oxide Synthase Type II
Permeation
Computer Simulation
Sprague Dawley Rats
Half-Life
tryptanthrine
In Vitro Techniques
Rats
Permeability
Assays
Nitric Oxide
Anti-Inflammatory Agents

Keywords

  • blood-brain barrier (BBB)
  • pharmacokinetics (PK)
  • tryptanthrin
  • UPLC-MS/MS
  • validation

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine

Cite this

Jähne, E. A., Eigenmann, D. E., Sampath, C., Butterweck, V., Culot, M., Cecchelli, R., ... Oufir, M. (2016). Pharmacokinetics and in Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin. Planta Medica, 82(11-12), 1021-1029. https://doi.org/10.1055/s-0042-105295

Pharmacokinetics and in Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin. / Jähne, Evelyn A.; Eigenmann, Daniela E.; Sampath, Chethan; Butterweck, Veronika; Culot, Maxime; Cecchelli, Roméo; Gosselet, Fabien; Walter, Fruzsina R.; Deli, M.; Smieško, Martin; Hamburger, Matthias; Oufir, Mouhssin.

In: Planta Medica, Vol. 82, No. 11-12, 01.07.2016, p. 1021-1029.

Research output: Contribution to journalArticle

Jähne, EA, Eigenmann, DE, Sampath, C, Butterweck, V, Culot, M, Cecchelli, R, Gosselet, F, Walter, FR, Deli, M, Smieško, M, Hamburger, M & Oufir, M 2016, 'Pharmacokinetics and in Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin', Planta Medica, vol. 82, no. 11-12, pp. 1021-1029. https://doi.org/10.1055/s-0042-105295
Jähne EA, Eigenmann DE, Sampath C, Butterweck V, Culot M, Cecchelli R et al. Pharmacokinetics and in Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin. Planta Medica. 2016 Jul 1;82(11-12):1021-1029. https://doi.org/10.1055/s-0042-105295
Jähne, Evelyn A. ; Eigenmann, Daniela E. ; Sampath, Chethan ; Butterweck, Veronika ; Culot, Maxime ; Cecchelli, Roméo ; Gosselet, Fabien ; Walter, Fruzsina R. ; Deli, M. ; Smieško, Martin ; Hamburger, Matthias ; Oufir, Mouhssin. / Pharmacokinetics and in Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin. In: Planta Medica. 2016 ; Vol. 82, No. 11-12. pp. 1021-1029.
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