Zur Kurzanzeige

dc.contributor.authorJähne, E
dc.contributor.authorEigenmann, D
dc.contributor.authorSampath, C
dc.contributor.authorButterweck, Veronika
dc.contributor.authorCulot, M
dc.contributor.authorCecchelli, R
dc.contributor.authorGosselet, F
dc.contributor.authorWalter, F. R.
dc.contributor.authorDeli, MA
dc.contributor.authorSmiesko, M
dc.contributor.authorHamburger, M
dc.contributor.authorOufir, M
dc.date.accessioned2016-12-13T10:14:37Z
dc.date.available2016-12-13T10:14:37Z
dc.date.issued2016
dc.identifier.doi10.1055/s-0042-105295
dc.identifier.urihttp://hdl.handle.net/11654/23688
dc.description.abstractThe 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.
dc.description.urihttps://www.ncbi.nlm.nih.gov/pubmed/27093249
dc.language.isoen
dc.relation.ispartofPlanta Medica
dc.accessRightsAnonymous
dc.subjecttryptanthrin
dc.subjectUPLC-MS/MS
dc.subjectvalidation
dc.subjectpharmacokinetics (PK)
dc.subjectblood-brain barrier (BBB)
dc.titlePharmacokinetics and in vitro blood-brain barrier screening of the plant-derived alkaloid tryptanthrin
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume82
dc.issue11-12
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.pagination1021-1029
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


Dateien zu dieser Ressource

DateienGrösseFormatAnzeige

Zu diesem Eintrag gibt es keine Dateien.

Der Eintrag erscheint in:

Zur Kurzanzeige