Epilepsies – encompassing a variety of neurological disorders of diverse etiology that have spontaneous, recurrent seizures as a common symptom – affect approximately 1% of the population. While numerous antiseizure drugs (ASDs) have been developed, these are only effective in 70% of epilepsy patients, leaving at least 20 million epilepsy patients worldwide without effective medication. In an ongoing effort to explore the potential of medicinal plants to provide novel drug leads and/or novel botanical drugs for the treatment of epilepsies, we and others have recently established the utility of zebrafish epilepsy models for the rapid and microscale in vivo screening and bioassay-guided fractionation of secondary metabolite extracts of medicinal plants [1].Several phytochemicals with antiseizure activity have been identified to date, including coumarins [2].
Here, we describe the in vivo characterization of the antiseizure activity of main furanocoumarin constituents, isolated from the methanolic extract of Peucedanum alsaticum L. (Apiaceae) using high-performance countercurrent chromatography (HPCCC). Immiscible mixture of solvents heptane, ethyl acetate, methanol and water (v/v 3:1:3:1) was successfully used in reversed phase mode to achieve 12,79 mg of bergamottin and 24,22 mg of lucidafuranocoumarin A. Both compounds exhibited antiseizure activity in zebrafish epilepsy model based on the GABAA antagonist pentylenetetrazol (PTZ), which causes zebrafish larvae to exhibit increased locomotor activity, seizure-like behavior, and epileptiform electrographic activity [3]. Lucidafuranocoumarin A exhibited more potent antiseizure activity, inhibiting 69% of PTZ-induced seizures at its maximum tolerated concentration (MTC) of 16 µM. Further experiments will seek to validate these findings through electrophysiological analysis in zebrafish and equivalent experiments in mouse epilepsy models.
Acknowledgments: This work was supported by Preludium 11 grant 2016/21/N/NZ4/03658 from the National Science Center (NCN) of Poland.
References
- Challal et al., Chimia2012, 66:229-32.
- Skalicka-Woźniaket al., Pharmacol. Res. 2016, 103:188-203.
- Afrikanovaet al., PLoS ONE 2013, 8:e54166.