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

• DOI: 10.1021/jf301511m
• Publication Date: 2012-07-27T15:15:00Z
• Authors: Zaijun Zhang; Wei Cui; Guohui Li; Shuai Yuan; Daping Xu; Maggie P.M. Hoi; Zhixiu Lin; Juan Dou; Yifan Han; Simon M.Y. Lee
• Keywords: Baicalein; KEAP1; MG132; Cytoprotection; LY294002

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