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ZIRC
ZFIN ID: ZDB-PUB-140213-21
Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy
Orellana-Paucar, A.M., Afrikanova, T., Thomas, J., Aibuldinov, Y.K., Dehaen, W., de Witte, P.A., and Esguerra, C.V.
Date: 2013
Source: PLoS One 8(12): e81634 (Journal)
Registered Authors: Esguerra, Camila V.
Keywords: none
MeSH Terms:
  • Animals
  • Anticonvulsants/pharmacokinetics*
  • Anticonvulsants/pharmacology
  • Behavior, Animal/drug effects
  • Blood-Brain Barrier*
  • Brain/drug effects*
  • Brain/metabolism
  • Brain/physiopathology
  • Brain-Derived Neurotrophic Factor/genetics
  • Brain-Derived Neurotrophic Factor/metabolism
  • Disease Models, Animal
  • Gene Expression Regulation/drug effects
  • Injections, Intraperitoneal
  • Ketones/pharmacokinetics*
  • Ketones/pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity/drug effects
  • Pentylenetetrazole
  • Postural Balance/drug effects
  • Proto-Oncogene Proteins c-fos/genetics
  • Proto-Oncogene Proteins c-fos/metabolism
  • Seizures/chemically induced
  • Seizures/drug therapy*
  • Seizures/metabolism
  • Seizures/physiopathology
  • Sesquiterpenes/pharmacokinetics*
  • Sesquiterpenes/pharmacology
  • Zebrafish
PubMed: 24349101 Full text @ PLoS One
ABSTRACT

In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

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