RGD Reference Report - Baicalein Protects against 6-OHDA-Induced Neurotoxicity through Activation of Keap1/Nrf2/HO-1 and Involving PKCalpha and PI3K/AKT Signaling Pathways. - Rat Genome Database

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Baicalein Protects against 6-OHDA-Induced Neurotoxicity through Activation of Keap1/Nrf2/HO-1 and Involving PKCalpha and PI3K/AKT Signaling Pathways.

Authors: Zhang, Z  Cui, W  Li, G  Yuan, S  Xu, D  Hoi, MP  Lin, Z  Dou, J  Han, Y  Lee, SM 
Citation: Zhang Z, etal., J Agric Food Chem. 2012 Aug 9.
RGD ID: 6892950
Pubmed: PMID:22838648   (View Abstract at PubMed)
DOI: DOI:10.1021/jf301511m   (Journal Full-text)

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, PKCalpha 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 PKCalpha and PI3K/AKT signaling pathway. Ultimately, the neuroprotective effects of baicalein may endue baicalein as a promising candidate for the prevention of PD.

Objects referenced in this article
Gene Keap1 Kelch-like ECH-associated protein 1 Rattus norvegicus

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