PUBLICATION
The Influence of Palmatine Isolated from Berberis sibiricaRadix on Pentylenetetrazole-Induced Seizures in Zebrafish
- Authors
- Gawel, K., Kukula-Koch, W., Nieoczym, D., Stepnik, K., Ent, W.V., Banono, N.S., Tarabasz, D., Turski, W.A., Esguerra, C.V.
- ID
- ZDB-PUB-200521-3
- Date
- 2020
- Source
- Cells 9(5): (Journal)
- Registered Authors
- Banono, Nancy, Esguerra, Camila V., Gawel, Kinga Aurelia
- Keywords
- Berberis sibirica radix, EEG, anticonvulsant activity, berberine, isolation, locomotor activity, palmatine, pentylenetetrazole, seizures, zebrafish
- MeSH Terms
-
- Locomotion/drug effects
- Proto-Oncogene Proteins c-fos/metabolism
- Electroencephalography
- Berberine Alkaloids/chemistry
- Berberine Alkaloids/pharmacology
- Berberine Alkaloids/therapeutic use*
- Zebrafish
- Berberine/chemistry
- Larva/drug effects
- Pentylenetetrazole/pharmacology
- Pentylenetetrazole/therapeutic use*
- Animals
- Behavior, Animal/drug effects
- Brain-Derived Neurotrophic Factor/metabolism
- Plant Extracts/pharmacology
- Blood-Brain Barrier/pathology
- Quantitative Structure-Activity Relationship
- Berberis/chemistry*
- Seizures/chemically induced*
- Seizures/drug therapy*
- PubMed
- 32429356 Full text @ Cells
Citation
Gawel, K., Kukula-Koch, W., Nieoczym, D., Stepnik, K., Ent, W.V., Banono, N.S., Tarabasz, D., Turski, W.A., Esguerra, C.V. (2020) The Influence of Palmatine Isolated from Berberis sibiricaRadix on Pentylenetetrazole-Induced Seizures in Zebrafish. Cells. 9(5):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping