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Pinostrobin Exerts Neuroprotective Actions in Neurotoxin-Induced Parkinson's Disease Models through Nrf2 Induction
Li, Chuwen1; Tang, Benqin1,2; Feng, Yu1; Tang, Fan1; Hoi, Maggie Pui-Man1; Su, Ziren3; Lee, Simon Ming-Yuen1
2018-08-08
Source PublicationJOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
ISSN0021-8561
Volume66Issue:31Pages: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 upregulation 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.

KeywordPinostrobin Parkinson's Disease Neurotoxin Nrf2
DOI10.1021/acs.jafc.8b02607
URLView the original
Indexed BySCI
Language英语
WOS Research AreaAgriculture ; Chemistry ; Food Science & Technology
WOS SubjectAgriculture, Multidisciplinary ; Chemistry, Applied ; Food Science & Technology
WOS IDWOS:000441476400012
PublisherAMER CHEMICAL SOC
Fulltext Access
Citation statistics
Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China;
2.Shunde Polytech, Dept Med Sci, Shunde, Peoples R China;
3.Guangzhou Univ Chinese Med, Math Engn Acad Chinese Med, Guangdong Prov Key Lab New Drug Dev & Res Chinese, Guangzhou, Guangdong, Peoples R China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Li, Chuwen,Tang, Benqin,Feng, Yu,et al. Pinostrobin Exerts Neuroprotective Actions in Neurotoxin-Induced Parkinson's Disease Models through Nrf2 Induction[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2018,66(31):8307-8318.
APA Li, Chuwen.,Tang, Benqin.,Feng, Yu.,Tang, Fan.,Hoi, Maggie Pui-Man.,...&Lee, Simon Ming-Yuen.(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.
MLA Li, Chuwen,et al."Pinostrobin Exerts Neuroprotective Actions in Neurotoxin-Induced Parkinson's Disease Models through Nrf2 Induction".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 66.31(2018):8307-8318.
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