title: Neuroprotective Effects of Paeoniflorin on 6-OHDA-Lesioned Rat Model of Parkinson's Disease.
abstract: Paeoniflorin (PF) is the main active component extracted from the roots of Paeonialactiflora, a traditional Chinese medicine used for the treatment of neurodegenerative disorders, especially Parkinson's disease (PD). The degeneration of dopaminergic (DA-) neurons in PD may be caused by pathological activation of acid-sensing ion channels (ASICs). Thus, we designed a series of experiments to evaluate the therapeutic effects of PF and to test whether its effects are related to its inhibitory effect on ASIC1a. We found that systemic administration of PF or ASICs blockers (psalmotoxin-1 and amiloride) improved behavioral symptoms, delayed DA-neuronal loss and attenuated the reduction of dopamine (DA) and its metabolites in a rat model of 6-hydroxydopamine (6-OHDA)-induced PD. In addition, our data showed that PF, like ASICs blockers, regulated the expression of ASIC1a, decreased the level of α-synuclein (α-SYN), and improved autophagic dysfunction. Further experiments showed that ASIC1a knockdown down-regulated the α-SYN level and alleviated the autophagic injury in the 6-OHDA-treated ASIC1a-silenced PC12 cells. In summary, these findings indicate that PF enhanced the autophagic degradation of α-SYN and, thus, protected DA-neurons against the neurotoxicity caused by 6-OHDA. These findings also provide experimental evidence that PF may be a neuroprotectant for PD by acting on ASIC1a and that ASIC1a may be involved in the pathogenesis of PD.
authors.affiliation: Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.|Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Gu
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Cai-Yi
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Cheng-Jie
authors.initials: CJ
authors.lastname: Mao
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Yang
authors.affiliation: Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Hu
authors.affiliation: Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China. liuchunfeng@suda.edu.cn.|Institute of Neuroscience, Soochow University, Suzhou, 215123, China. liuchunfeng@suda.edu.cn.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D006027:Glycosides
chemical_list: D062565:Acid Sensing Ion Channels; D001952:Bridged-Ring Compounds; D004298:Dopamine; D005960:Glucosides; D039821:Monoterpenes; D018696:Neuroprotective Agents; D016627:Oxidopamine; C015423:peoniflorin; D006027:Glycosides
keywords: 6-OHDA; ASIC1a; Autophagy; Paeoniflorin; Parkinson’s disease; α-SYN