PUBLICATION
Pinostrobin exerts neuroprotective actions in neurotoxin-induced Parkinson's disease models through Nrf2 induction
- Authors
- Li, C., Tang, B., Feng, Y., Tang, F., Pui Man Hoi, M., Su, Z., Lee, S.M.
- ID
- ZDB-PUB-180703-1
- Date
- 2018
- Source
- Journal of Agricultural and Food Chemistry 66(31): 8307-8318 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology
- 1-Methyl-4-phenylpyridinium/pharmacology
- Animals
- Antioxidants/metabolism
- Apoptosis/drug effects
- Cell Line, Tumor
- Disease Models, Animal
- Dopaminergic Neurons/drug effects
- Flavanones/administration & dosage*
- Gene Knockout Techniques
- Humans
- NF-E2-Related Factor 2/deficiency
- NF-E2-Related Factor 2/genetics
- NF-E2-Related Factor 2/physiology
- Neuroblastoma
- Neuroprotective Agents/administration & dosage*
- Oxidative Stress/drug effects
- Parkinson Disease/drug therapy
- Parkinson Disease, Secondary/drug therapy*
- Parkinson Disease, Secondary/etiology
- Zebrafish
- PubMed
- 29961319 Full text @ J. Agric. Food Chem.
Citation
Li, C., Tang, B., Feng, Y., Tang, F., Pui Man Hoi, M., Su, Z., Lee, S.M. (2018) Pinostrobin exerts neuroprotective actions in neurotoxin-induced Parkinson's disease models through Nrf2 induction. Journal of Agricultural and Food Chemistry. 66(31):8307-8318.
Abstract
The aim of the present study was to assess the neuroprotective effects of pinostrobin (PSB), a dietary bioflavonoid, and its underlying mechanisms in neurotoxin-induced Parkinson's disease (PD) models. First, PSB could attenuate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons and improve behavior deficiency in zebrafish, supporting its potential neuroprotective actions in vivo. Next, PSB could decreased apoptosis and death in the 1-methyl-4-phenylpyridinium (MPP+)-intoxicated SH-SY5Y cells, evidenced by MTT, LDH, Annexin V-FITC/PI, and DNA fragmentation assay. PSB also blocked MPP+-induced apoptotic cascades, including loss of mitochondrial membrane potential, activation of caspase 3, and reduced ratio of Bcl-2/Bax. In addition, PSB suppressed MPP+-induced oxidative stress but increased antioxidant enzymes, evidenced by decrease of reactive oxygen species generation and lipid peroxidation and up-regulation of GSH-Px, SOD, CAT, GSH/GSSG, and NAD/NADH. Further investigations showed that PSB significantly enhanced Nrf2 expression and nuclear accumulation, improved ARE promoter activity and up-regulated expression of HO-1 and GCLC. Furthermore, Nrf2 knockdown via specific Nrf2 siRNA abolished PSB-induced antioxidative and antiapoptotic effects against MPP+ insults. Interestingly, we then found that PSB promoted phosphorylation of PI3K/AKT and ERK, and pharmacological inhibition of PI3K/AKT or ERK signaling diminished PSB-induced Nrf2/ARE activation and protective actions. In summary, PSB confers neuroprotection against MPTP/MPP+-induced neurotoxicity in PD models. Promoting activation of Nrf2/ARE signaling contributes to PSB-mediated antioxidative and neuroprotective actions, which, in part, is mediated by PI3K/AKT and ERK.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping