title: n-butylidenephthalide protects against dopaminergic neuron degeneration and α-synuclein accumulation in Caenorhabditis elegans models of Parkinson's disease.
abstract: BACKGROUND
  Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system that impairs motor skills and cognitive function. To date, the disease has no effective therapies. The identification of new drugs that provide benefit in arresting the decline seen in PD patients is the focus of much recent study. However, the lengthy time frame for the progression of neurodegeneration in PD increases both the time and cost of examining potential therapeutic compounds in mammalian models. An alternative is to first evaluate the efficacy of compounds in Caenorhabditis elegans models, which reduces examination time from months to days. n-Butylidenephthalide is the naturally-occurring component derived from the chloroform extract of Angelica sinensis. It has been shown to have anti-tumor and anti-inflammatory properties, but no reports have yet described the effects of n-butylidenephthalide on PD. The aim of this study was to assess the potential for n-butylidenephthalide to improve PD in C. elegans models.
  
  
  RESULTS
  In the current study, we employed a pharmacological strain that expresses green fluorescent protein specifically in dopaminergic neurons (BZ555) and a transgenic strain that expresses human α-synuclein in muscle cells (OW13) to investigate the antiparkinsonian activities of n-butylidenephthalide. Our results demonstrate that in PD animal models, n-butylidenephthalide significantly attenuates dopaminergic neuron degeneration induced by 6-hydroxydopamine; reduces α-synuclein accumulation; recovers lipid content, food-sensing behavior, and dopamine levels; and prolongs life-span of 6-hydroxydopamine treatment, thus revealing its potential as a possible antiparkinsonian drug. n-Butylidenephthalide may exert its effects by blocking egl-1 expression to inhibit apoptosis pathways and by raising rpn-6 expression to enhance the activity of proteasomes.
  
  
  CONCLUSIONS
  n-Butylidenephthalide may be one of the effective neuroprotective agents for PD.
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan ; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ru-Huei
authors.initials: RH
authors.lastname: Fu
authors.affiliation: Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Horng-Jyh
authors.initials: HJ
authors.lastname: Harn
authors.affiliation: Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chang-Shi
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Chang
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Yue-Mi
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Jing-En
authors.initials: JE
authors.lastname: Huang
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Rong-Jhu
authors.initials: RJ
authors.lastname: Li
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Sung-Yu
authors.initials: SY
authors.lastname: Tsai
authors.affiliation: Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Huey-Shan
authors.initials: HS
authors.lastname: Hung
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan ; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan ; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan ; Department of Neurosurgery, China Medical University Beigang Hospital, Yunlin, Taiwan ; Department of Neurosurgery, Tainan Municipal An-Nan Hospital-China Medical University, Tainan, Taiwan.
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Wang
mesh_terms: D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D008136:Longevity / Q000187:drug effects; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D051844:alpha-Synuclein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D029742:Caenorhabditis elegans Proteins; D004365:Drugs, Chinese Herbal; C112486:EGL-1 protein, C elegans; D010796:Phthalic Anhydrides; D012097:Repressor Proteins; D051844:alpha-Synuclein; D016627:Oxidopamine; C044613:angelicae sinensis extract; D046988:Proteasome Endopeptidase Complex; C575985:RPN-6.1 protein, C elegans; C026105:butylidenephthalide; D004298:Dopamine