Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish

被引：70

作者：

Chong, Cheong-Meng ^{[1
]}

Zhou, Zhong-Yan ^{[1
]}

Razmovski-Naumovski, Valentina ^{[2
,3
]}

Cui, Guo-Zhen ^{[1
]}

Zhang, Lun-Qing ^{[1
]}

Sa, Fei ^{[1
]}

Hoi, Pui-Man ^{[1
]}

Chan, Kelvin ^{[2
,3
]}

Lee, Simon Ming-Yuen ^{[1
]}

机构：

[1] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Peoples R China

[2] Univ Sydney, Fac Pharm, Penrith, NSW, Australia

[3] Univ Western Sydney, Sch Sci & Hlth, Ctr Complementary Med Res, Penrith, NSW 2751, Australia

来源：

NEUROSCIENCE LETTERS | 2013年 / 543卷

关键词：

Neurodegeneration; ROS; Zebrafish; 6-OHDA; HEME OXYGENASE-1 EXPRESSION; TRANSCRIPTION FACTOR; RESPONSIVE ELEMENT; OXIDATIVE STRESS; PATHWAY; ACID; GENE; ACTIVATION; MECHANISMS; NEUROPROTECTION;

D O I：

10.1016/j.neulet.2013.02.069

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The overproduction of reactive oxygen species (ROS) has been implicated in the development of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Previous studies have indicated that danshensu (beta-3,4-dihydroxyphenyl-lactic acid), a main hydrophilic component of the Chinese materia medica Radix Salviae Miltiorrhizae (Danshen, Pharmacopoeia of PR China), has ROS scavenging and antioxidant activities, however its mechanism of action was not clear. In this study, we investigated whether the protective effects of danshensu against neurotoxin 6-hydroxydopamine (6-OHDA)-induced oxidative stress involved the Nrf2/HO-1 pathways. Pretreatment with danshensu in PC12 cells significantly attenuated 6-OHDA-induced cytotoxicity and the production of ROS. Danshensu activated the nuclear translocation of Nrf2 to increase heme oxygenase-1 (HO-1), conferring protection against ROS. Danshensu induced the phosphorylation of Akt, and its cytoprotective effect was abolished by PI3K, Akt and HO-1 inhibitors. These results confirmed the crucial role of PI3K/Akt and HO-1 signaling pathways as the underlying mechanistic action of danshensu. Taken together, the results suggest that danshensu enhances HO-1 expression to suppress 6-OHDA-induced oxidative damage via PI3K/Akt/Nrf2 signaling pathways. Moreover, 6-OHDA-induced dopaminergic neuronal loss in zebrafish could be reduced by danshensu, further supporting the neuroprotective potential of danshensu. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：121 / 125

页数：5

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