Zebrafish bioassay-guided isolation of the anticonvulsant compounds from Cyperus articulatus

Epilepsy is a common CNS disorder usually treated by commercial antiepileptic drugs (AEDs) in western countries. A large number of AEDs are available and preferentially used according to the type of seizures. However, 30% of patients suffering from epilepsy remain pharmaco-resistant to the current treatments. Medicinal plants are also widely used in low and middle-income countries to treat epilepsy and the decoction of Cyperus articulatus roots is a known and traditional remedy to heal epilepsy in Cameroon. Previous studies have demonstrated its in-vivo activity in a mice model [1]. In order to identify the active principles, a zebrafish epilepsy model well suited for bioguided-assay fractionation was chosen [2]. Extraction of the roots by solvents of increasing polarity indicated a high anticonvulsant activity in the hexanic extract (HE). Microfractionation of the HE by normal phase flash chromatography combined with a zebrafish bioguided-assay enable to localize LC-peaks responsible for the bioactivity. The isolation of these compounds at larger scale was targeted based on their physico-chemical profiles and resulted in the isolation of four bioactive terpenoids reducing drastically zebrafish induced seizures up to 81%. Their chemical structures were characterized by classical spectroscopic methods including HRMS and NMR. Additionally, the parallel artificial membrane permeability (PAMPA) absorption of the HE has been performed and confirmed the passive permeation of major active compounds in the gastrointestinal tract (GIT) as well as in the blood brain barrier (BBB). This study provides further proof supporting the traditional use of this plant in the treatment of epilepsy.

[1] Ngo Bum E, Rakotonirina A, Rakotonirina SV, Herrling P. J Ethnopharmacol 2003; 87: 27 – 34

[2] Challal S, Queiroz EF, Debrus B, Kloeti W, Guillarme D, Gupta MP, Wolfender JL. Planta Med 2015; 81: 1636 – 1643