Baicalein Protects against 6-OHDA-Induced Neurotoxicity through Activation of Keap1/Nrf2/HO-1 and Involving PKC alpha and PI3K/AKT Signaling Pathways
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香港中文大學研究人員

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摘要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, PKC alpha 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 PKC alpha and PI3K/AKT signaling pathway. Ultimately, the neuroprotective effects of baicalein may endue baicalein as a promising candidate for the prevention of PD.
著者Zhang ZJ, Cui W, Li GH, Yuan S, Xu DP, Hoi MPM, Lin ZX, Dou J, Han YF, Lee SMY
期刊名稱Journal of Agricultural and Food Chemistry
出版年份2012
月份8
日期22
卷號60
期次33
出版社AMER CHEMICAL SOC
頁次8171 - 8182
國際標準期刊號0021-8561
電子國際標準期刊號1520-5118
語言英式英語
關鍵詞6-OHDA; baicalein; neuroprotection; Nrf2; oxidative stress; Parkinson's disease
Web of Science 學科類別Agriculture; Agriculture, Multidisciplinary; AGRICULTURE, MULTIDISCIPLINARY; Chemistry; Chemistry, Applied; CHEMISTRY, APPLIED; Food Science & Technology; FOOD SCIENCE & TECHNOLOGY

上次更新時間 2020-07-07 於 02:05