Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish
- Authors
- Chong, C.M., Zhou, Z.Y., Razmovski-Naumovski, V., Cui, G.Z., Zhang, L.Q., Sa, F., Hoi, P.M., Chan, K., and Lee, S.M.
- ID
- ZDB-PUB-130416-25
- Date
- 2013
- Source
- Neuroscience letters 543: 121-5 (Journal)
- Registered Authors
- Keywords
- neurodegeneration, ROS, zebrafish, 6-OHDA
- MeSH Terms
-
- Animals
- Antioxidant Response Elements
- Cell Death/drug effects
- Dopaminergic Neurons/drug effects
- Dopaminergic Neurons/pathology
- Drugs, Chinese Herbal/pharmacology
- Heme Oxygenase-1/metabolism
- Lactates/pharmacology*
- Lactates/therapeutic use
- NF-E2-Related Factor 2/metabolism
- Neurons/drug effects*
- Neurons/pathology
- Neuroprotective Agents/pharmacology*
- Neuroprotective Agents/therapeutic use
- Oxidative Stress/drug effects
- Oxidopamine*
- PC12 Cells
- Parkinson Disease/drug therapy
- Parkinson Disease/etiology
- Parkinson Disease/pathology*
- Phosphatidylinositol 3-Kinases/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- Rats
- Reactive Oxygen Species/metabolism
- Signal Transduction
- Zebrafish
- PubMed
- 23562886 Full text @ Neurosci. Lett.
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.