PUBLICATION
Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways
- Authors
- Zhang, C., Li, C., Chen, S., Li, Z., Jia, X., Wang, K., Bao, J., Liang, Y., Wang, X., Chen, M., Li, P., Su, H., Wan, J.B., Lee, S.M., Liu, K., He, C.
- ID
- ZDB-PUB-161113-11
- Date
- 2017
- Source
- Redox Biology 11: 1-11 (Journal)
- Registered Authors
- Wang, Kai
- Keywords
- Berberine, Hormesis, Neuroprotection, PC12 cells, Zebrafish
- MeSH Terms
-
- Animals
- Antioxidants/administration & dosage*
- Apoptosis/drug effects
- Berberine/administration & dosage*
- Cell Survival/drug effects
- Disease Models, Animal
- Dopaminergic Neurons/drug effects
- Dopaminergic Neurons/pathology
- Heme Oxygenase-1/genetics
- Hormesis/drug effects
- Hormesis/genetics
- Humans
- NF-E2-Related Factor 2/genetics
- Neuroprotective Agents/administration & dosage*
- Oncogene Protein v-akt/genetics
- Oxidopamine/toxicity
- PC12 Cells
- Parkinson Disease, Secondary/drug therapy*
- Parkinson Disease, Secondary/genetics
- Parkinson Disease, Secondary/metabolism
- Parkinson Disease, Secondary/pathology
- Phosphatidylinositol 3-Kinases/genetics
- Proto-Oncogene Proteins c-bcl-2/genetics
- Rats
- Reactive Oxygen Species/metabolism
- Signal Transduction/drug effects
- Zebrafish
- PubMed
- 27835779 Full text @ Redox Biol.
Citation
Zhang, C., Li, C., Chen, S., Li, Z., Jia, X., Wang, K., Bao, J., Liang, Y., Wang, X., Chen, M., Li, P., Su, H., Wan, J.B., Lee, S.M., Liu, K., He, C. (2017) Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways. Redox Biology. 11:1-11.
Abstract
Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping