The Influence of Palmatine Isolated from <i>Berberis sibirica Radix</i> on Pentylenetetrazole-Induced Seizures in Zebrafish
Kinga Gawel,
Wirginia Kukula-Koch,
Dorota Nieoczym,
Katarzyna Stepnik,
Wietske van der Ent,
Nancy Saana Banono,
Dominik Tarabasz,
Waldemar A. Turski,
Camila V. Esguerra
Affiliations
Kinga Gawel
Chemical Neuroscience Group, Faculty of Medicine, Centre for Molecular Medicine Norway, University of Oslo, Gaustadalléen 21, 0349 Oslo, Norway
Wirginia Kukula-Koch
Chair and Department of Pharmacognosy, Medical University of Lublin, 1, Chodzki Str. 1, 20-093 Lublin, Poland
Dorota Nieoczym
Department of Animal Physiology and Pharmacology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka Str. 19, 20-033 Lublin, Poland
Katarzyna Stepnik
Department of Physical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University, Pl. M. Curie-Skłodowskiej 3/243, 20-031 Lublin, Poland
Wietske van der Ent
Chemical Neuroscience Group, Faculty of Medicine, Centre for Molecular Medicine Norway, University of Oslo, Gaustadalléen 21, 0349 Oslo, Norway
Nancy Saana Banono
Chemical Neuroscience Group, Faculty of Medicine, Centre for Molecular Medicine Norway, University of Oslo, Gaustadalléen 21, 0349 Oslo, Norway
Dominik Tarabasz
Chair and Department of Pharmacognosy, Medical University of Lublin, 1, Chodzki Str. 1, 20-093 Lublin, Poland
Waldemar A. Turski
Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego Str. 8b, 20-090 Lublin, Poland
Camila V. Esguerra
Chemical Neuroscience Group, Faculty of Medicine, Centre for Molecular Medicine Norway, University of Oslo, Gaustadalléen 21, 0349 Oslo, Norway
Palmatine (PALM) and berberine (BERB) are widely identified isoquinoline alkaloids among the representatives of the Berberidaceae botanical family. The antiseizure activity of BERB was shown previously in experimental epilepsy models. We assessed the effect of PALM in a pentylenetetrazole (PTZ)-induced seizure assay in zebrafish, with BERB as an active reference compound. Both alkaloids were isolated from the methanolic root extract of Berberis sibirica by counter-current chromatography, and their ability to cross the blood–brain barrier was determined via quantitative structure–activity relationship assay. PALM exerted antiseizure activity, as confirmed by electroencephalographic analysis, and decreased c-fos and bdnf levels in PTZ-treated larvae. In a behavioral assay, PALM dose-dependently decreased PTZ-induced hyperlocomotion. The combination of PALM and BERB in ED16 doses revealed hyperadditive activity towards PTZ-induced hyperlocomotion. Notably, we have indicated that both alkaloids may exert their anticonvulsant activity through different mechanisms of action. Additionally, the combination of both alkaloids in a 1:2.17 ratio (PALM: BERB) mimicked the activity of the pure extract, which indicates that these two active compounds are responsible for its anticonvulsive activity. In conclusion, our study reveals for the first time the anticonvulsant activity of PALM and suggests the combination of PALM and BERB may have higher therapeutic value than separate usage of these compounds.
