The Influence of Palmatine Isolated from Berberis sibiricaRadix on Pentylenetetrazole-Induced Seizures in Zebrafish.

Kinga Gawel,Waldemar A Turski,Nancy Saana Banono,Dorota Nieoczym,Wietske Van Der Ent,Dominik Tarabasz,Wirginia Kukula-Koch,Camila V Esguerra,Katarzyna Stepnik

doi:10.3390/cells9051233

Kinga Gawel, Waldemar A Turski + Show 7 more

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https://doi.org/10.3390/cells9051233

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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.

Highlights

Epilepsy is a common neurological disorder that affects approximately 65 million people worldwide, regardless of their age, sex, descent, or economic status [1]
Based on the analysis of variance of our Quantitative Structure–Activity Relationship (QSAR) model, it can be assumed that the proposed model will be suitable for other isoquinoline alkaloids of plant origin from the subgroup of protoberberines
The limitations of the model have been examined by applying the applicability domain (AD) [46] based on the results presented in our previous paper [47]

Summary

Introduction

Epilepsy is a common neurological disorder that affects approximately 65 million people worldwide, regardless of their age, sex, descent, or economic status [1] It is manifested by repetitive seizures caused. It is manifested by repetitive seizures caused by abnormal electrical activity of neurons in the central nervous system (CNS). Available antiseizure drugs (ASDs), which are the main treatment for epilepsy, suppress antiseizure drugs (ASDs), which are the main treatment for epilepsy, suppress symptoms of the disease symptoms of the disease (convulsions), but do not alleviate the process of epileptogenesis.

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