title: Astragaloside IV prevents MPP⁺-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production.
abstract: Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of PD. Previous studies have revealed that Astragaloside IV (AS-IV) can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative disease. In this study, we investigated whether AS-IV protect against 1-methyl-4-phenylpyridnium ion (MPP(+))-induced dopaminergic neurotoxicity in SH-SY5Y cells and determined the mechanism of AS-IV neuroprotection. We found that pretreatment with AS-IV significantly reversed the loss of cell viability, nuclear condensation, the generation of intracellular reactive oxygen species (ROS), and the increase in Bax/Bcl-2 ratio and the activity of caspase-3 induced by MPP(+). Our study suggests that the neuroprotective effect of AS-IV is related to mechanisms including ROS production and the inhibition of Bax-mediated pathway. The present study supports the notion that AS-IV may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as PD.
authors.affiliation: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Baqiao District, Xi'an, People's Republic of China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Ju-Lei
authors.initials: JL
authors.lastname: Wang
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Yao
authors.forename: Huai-Zhou
authors.initials: HZ
authors.lastname: Qin
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C052064:astragaloside A; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium