PUBLICATION
Anti-Inflammation Associated Protective Mechanism of Berberine and its Derivatives on Attenuating Pentylenetetrazole-Induced Seizures in Zebrafish
- Authors
- Zhang, B., Wang, L., Ji, X., Zhang, S., Sik, A., Liu, K., Jin, M.
- ID
- ZDB-PUB-200108-22
- Date
- 2020
- Source
- Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 15(2): 309-325 (Journal)
- Registered Authors
- Keywords
- Anti-inflammation, Anticonvulsant, Berberine, Epilepsy, PTZ, Zebrafish
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/therapeutic use*
- Anticonvulsants/therapeutic use
- Berberine/analogs & derivatives*
- Berberine/therapeutic use*
- Female
- Macrophages/drug effects
- Macrophages/metabolism
- Male
- Pentylenetetrazole/toxicity*
- Seizures/chemically induced*
- Seizures/metabolism
- Seizures/prevention & control*
- Zebrafish
- PubMed
- 31909440 Full text @ J. Neuroimmune Pharmacol.
Citation
Zhang, B., Wang, L., Ji, X., Zhang, S., Sik, A., Liu, K., Jin, M. (2020) Anti-Inflammation Associated Protective Mechanism of Berberine and its Derivatives on Attenuating Pentylenetetrazole-Induced Seizures in Zebrafish. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 15(2):309-325.
Abstract
Epileptic seizures are characterized by synchronized discharges of neurons, leading to the activation of inflammatory responses that in turn contributes to seizure progression. Berberine (BBR), a bioactive constituent extracted from berberis, has been known to relieve seizures in rodent models. In this study, we synthesized two derivatives of berberine (BBR-D1 and BBR-D2) to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity. We also investigated the underlying mechanism related to their anti-inflammatory effect during seizures. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives. Our results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures. From the tested compounds, BBR-D1 (the hydrophilic berberrubine) showed the strongest seizure reducing effect. Graphical Abstract Two derivatives of berberine (BBR-D1 and BBR-D2) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping