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Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish
Chong C.-M.1; Zhou Z.-Y.1; Razmovski-Naumovski V.2; Cui G.-Z.1; Zhang L.-Q.1; Sa F.1; Hoi P.-M.1; Chan K.2; Lee S.M.Y.1
2013-05-24
Source PublicationNeuroscience Letters
ISSN03043940 18727972
Volume543Pages:121-125
Abstract

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. © 2013 Elsevier Ireland Ltd.

Keyword6-ohda Neurodegeneration Ros Zebrafish
DOI10.1016/j.neulet.2013.02.069
URLView the original
Indexed BySCI
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000319646000024
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被引频次[WOS]:45   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
Affiliation1.Institute of Chinese Medical Sciences
2.The University of Sydney
First Author AffilicationInstitute of Chinese Medical Sciences
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Chong C.-M.,Zhou Z.-Y.,Razmovski-Naumovski V.,et al. Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish[J]. Neuroscience Letters,2013,543:121-125.
APA Chong C.-M..,Zhou Z.-Y..,Razmovski-Naumovski V..,Cui G.-Z..,Zhang L.-Q..,...&Lee S.M.Y..(2013).Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish.Neuroscience Letters,543,121-125.
MLA Chong C.-M.,et al."Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish".Neuroscience Letters 543(2013):121-125.
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