title: Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress.
abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by a persistent decline of dopaminergic (DA) neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum (ER) stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent anti-oxidative stress properties and protects against DA neuronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine (6-OHDA)-induced cytotoxicity by attenuating ER stress. Furthermore, treatment of a DA neuronal cell line (SN4741) and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results suggest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Dayun
authors.initials: D
authors.lastname: Feng
authors.affiliation: Research Center of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lai
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Tiejian
authors.initials: T
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. qianyang@fmmu.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018663:Adrenergic Agents; D005960:Glucosides; D018696:Neuroprotective Agents; D010636:Phenols; D016627:Oxidopamine; C009172:rhodioloside
keywords: 6-OHDA; ER stress; Neuroprotection; Parkinson’s disease; Salidroside