title: Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish.
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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, Avenue Padre Tomás Pereira S.J., Macao.
authors.forename: Cheong-Meng
authors.initials: CM
authors.lastname: Chong
authors.forename: Zhong-Yan
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Valentina
authors.initials: V
authors.lastname: Razmovski-Naumovski
authors.forename: Guo-Zhen
authors.initials: GZ
authors.lastname: Cui
authors.forename: Lun-Qing
authors.initials: LQ
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Sa
authors.forename: Pui-Man
authors.initials: PM
authors.lastname: Hoi
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D016923:Cell Death / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish
chemical_list: D004365:Drugs, Chinese Herbal; D007773:Lactates; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; C035055:3,4-dihydroxyphenyllactic acid; D016627:Oxidopamine; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt