title: Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5mg/kg, 12weeks). Baicalein (100mg/kg) was intraperitoneally injected from 7week to 12week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.affiliation: Department of Internal Medicine, Wuchang Hospital, Wuhan 430063, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huicong
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Lian
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Cuntai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Neurologische Klinik und Poliklinik, Klinikum der Universität München, Marchioninistr. 15, 81377 München, Germany; Munich Cluster for Systems Neurology, SyNergy, Germany.
authors.forename: Francisco
authors.initials: F
authors.lastname: Pan-Montojo
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhusuiqiang@hotmail.com.
authors.forename: Suiqiang
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000818:Animals; D044950:Flavanones / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D055503:Protein Multimerization / Q000187:drug effects*; D012402:Rotenone / Q000009:adverse effects* / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D044950:Flavanones; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D012402:Rotenone; C006680:baicalein
keywords: Baicalein; Flavonoid; Neurodegenerative disease; Parkinson's disease; Rotenone; α-Synuclein