PUBLICATION
Treatment of Parkinson's disease in Zebrafish model with a berberine derivative capable of crossing blood brain barrier, targeting mitochondria, and convenient for bioimaging experiments
- Authors
- Wang, L., Sheng, W., Tan, Z., Ren, Q., Wang, R., Stoika, R., Liu, X., Liu, K., Shang, X., Jin, M.
- ID
- ZDB-PUB-210804-6
- Date
- 2021
- Source
- Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 249: 109151 (Journal)
- Registered Authors
- Keywords
- 6-hydroxydopamine, MPTP, PC12, Parkinson's disease, Zebrafish
- MeSH Terms
-
- Animals
- Berberine/administration & dosage
- Berberine/chemistry
- Berberine/pharmacokinetics
- Berberine/pharmacology*
- Blood-Brain Barrier/drug effects*
- Brain/drug effects*
- Disease Models, Animal
- Dopaminergic Neurons/drug effects
- Dopaminergic Neurons/pathology
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian
- HeLa Cells
- Humans
- MPTP Poisoning/drug therapy
- MPTP Poisoning/etiology
- Microtubule-Associated Proteins/metabolism
- Mitochondria/drug effects
- Molecular Structure
- PC12 Cells
- Parkinson Disease/drug therapy*
- Protein Kinases/metabolism
- Rats
- Zebrafish/embryology
- PubMed
- 34343700 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Citation
Wang, L., Sheng, W., Tan, Z., Ren, Q., Wang, R., Stoika, R., Liu, X., Liu, K., Shang, X., Jin, M. (2021) Treatment of Parkinson's disease in Zebrafish model with a berberine derivative capable of crossing blood brain barrier, targeting mitochondria, and convenient for bioimaging experiments. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 249:109151.
Abstract
Berberine is a famous alkaloid extracted from Berberis plants and has been widely used as medications and functional food additives. Recent studies reveal that berberine exhibits neuroprotective activity in animal models of Parkinson's disease (PD), the second most prevalent neurodegenerative disorders all over the world. However, the actual site of anti-PD action of berberine remains largely unknown. To this end, we employed a fluorescently labeled berberine derivative BBRP to investigate the subcellular localization and blood brain barrier (BBB) permeability in a cellular model of PD and zebrafish PD model. Biological investigations revealed that BBRP retained the neuroprotective activity of berberine against PD-like symptoms in PC12 cells and zebrafish, such as protecting 6-OHDA induced cell death, relieving MPTP induced PD-like behavior and increasing dopaminergic neuron loss in zebrafish. We also found that BBRP could readily penetrate BBB and function in the brain of zebrafish suffering from PD. Subcellular localization study indicated that BBRP could rapidly and specifically accumulate in mitochondria of PC12 cells when it exerted anti-PD effect. In addition, BBRP could suppress accumulation of Pink1 protein and inhibit the overexpression of LC3 protein in 6-OHDA damaged cells. All these results suggested that the potential site of action of berberine is mitochondria in the brain under the PD condition. Therefore, the findings described herein would be useful for further development of berberine as an anti-PD drug.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping