Protective effects of salidroside in the MPTP/MPP(+)-induced model of Parkinson's disease through ROS-NO-related mitochondrion pathway.

Abstract

Parkinson's disease is a progressive neurodegenerative disease causing tremor, rigidity, bradykinesia, and gait impairment. Oxidative stress and mitochondrial dysfunction play important roles in the development of Parkinson disease. Salidroside (Sal), a phenylpropanoid glycoside isolated from Rhodiola rosea L., has potent antioxidant properties. Previous work from our group suggests that Sal might protect dopaminergic neurons through inhibition of reactive oxygen species (ROS) and nitric oxide (NO) generation. In the present study, we investigated the protective effects of Sal in MPTP/MPP(+) models of Parkinson's disease in an attempt to elucidate the underlying mechanism of protection. We found that Sal pretreatment protected dopaminergic neurons against MPTP/MPP(+)-induced toxicity in a dose-dependent manner by: (1) reducing the production of ROS-NO, (2) regulating the ratio of Bcl-2/Bax, (3) decreasing cytochrome-c and Smac release, and inhibiting caspase-3, caspas-6, and caspas-9 activation, and (4) reducing α-synuclein aggregation. The present study supports the hypothesis that Sal may act as an effective neuroprotective agent through modulation of the ROS-NO-related mitochondrial pathway in vitro and in vivo.

• Authors: Songhai Wang, Hong He, Lei Chen, Wei Zhang, Xiaojun Zhang, Jianzong Chen
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 51 Issue 2 Pg. 718-28 (Apr 2015) ISSN: 1559-1182 [Electronic] United States
• PMID: 24913834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucosides
• Neuroprotective Agents
• Phenols
• Reactive Oxygen Species
• Nitric Oxide
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• rhodioloside

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Glucosides (pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects, physiology)
• Parkinsonian Disorders (chemically induced, metabolism, prevention & control)
• Phenols (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects, physiology)