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Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways
Zhang Z.1,2,3; Cui W.4; Li G.5; Yuan S.1,2; Xu D.1,2; Hoi M.P.M.1,2; Lin Z.6; Dou J.7,8; Han Y.4; Lee S.M.Y.1,2
2012
Source PublicationJournal of Agricultural and Food Chemistry
ISSN218561
Volume60Issue:33Pages:8171
Abstract

Baicalein, one of the major flavonoids found in Scutellaria baicalensis Georgi, displays neuroprotective effects on experimental models of Parkinson's disease (PD) in vitro and in vivo. Although the antioxidative and/or anti-inflammatory activity of baicalein likely contributes to these neuroprotective effects, other modes of action remain largely uncharacterized. In the present study, baicalein pretreatment significantly prevented cells from 6-hydroxydopamine (6-OHDA)-induced damage by attenuating cellular apoptosis. However, post-treatment with baicalein did not show any restorative effect against 6-OHDA-induced cellular damage. We found that baicalein increased transcriptional factor NF-E2-related factor 2 (Nrf2)/hemo oxygenase 1(HO-1) protein expression and decreased Kelch-like ECH-associated protein 1 (Keap1) in a time- and concentration-dependent manner in PC12 cells. In addition, baicalein induced Nrf2 nuclear translocation and enhanced antioxidant response element (ARE) transcriptional activity, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, we demonstrated that cytoprotective effects of baicalein could be attenuated by Nrf2 siRNA transfection and the HO-1 inhibitor zinc protoporphyrin (Znpp) as well as the proteasome inhibitor MG132. Furthermore, PKCα and AKT protein phosphorylation were up-regulated by baicalein pretreatment, and selective inhibitors targeted to PKC, PI3K, and AKT could block the cytoprotective effects of baicalein. Taken together, our results indicate that baicalein prevented PC12 cells from 6-OHDA-induced oxidative damage via the activation of Keap1/Nrf2/HO-1, and it also involves the PKCα and PI3K/AKT signaling pathway. Ultimately, the neuroprotective effects of baicalein may endue baicalein as a promising candidate for the prevention of PD. © 2012 American Chemical Society.

DOIhttp://doi.org/10.1021/jf301511m
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:000307698900014
The Source to ArticleScopus
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Cited Times [WOS]:90   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLee S.M.Y.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine (University of Macau), Macao SAR, China
2.Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
3.Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine & New Drug Research, College of Pharmacy, Jinan University, Guangdong, China
4.Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong SAR, China
5.Department of Chemistry, Hong Kong University, Hong Kong SAR, China
6.School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
7.Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
8.Departments of Pharmacology and Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, United States
First Author AffilicationUniversity of Macau;  Institute of Chinese Medical Sciences
Corresponding Author AffilicationUniversity of Macau;  Institute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhang Z.,Cui W.,Li G.,et al. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways[J]. Journal of Agricultural and Food Chemistry,2012,60(33):8171.
APA Zhang Z..,Cui W..,Li G..,Yuan S..,Xu D..,...&Lee S.M.Y..(2012).Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways.Journal of Agricultural and Food Chemistry,60(33),8171.
MLA Zhang Z.,et al."Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways".Journal of Agricultural and Food Chemistry 60.33(2012):8171.
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