title: Cerebral potential biomarkers discovery and metabolic pathways analysis of α-synucleinopathies and the dual effects of Acanthopanax senticosus Harms on central nervous system through metabolomics analysis.
abstract: BACKGROUND
  Acanthopanax senticosus Harms (AS), also called "Ciwujia" in Chinese and "Siberian ginseng" in the Siberian Taiga region, is the herb used in traditional medicinal systems of China, Russia, Japan and Korea for the treatment of various nervous and cerebrovascular diseases.
  
  
  OBJECTIVE
  Our pre-study has showed that AS can significantly suppress α-synuclein overexpression and toxicity. Neuronal protein α-synuclein is a key player in the development of neurodegenerative diseases called α-synucleinopathies. Identifying the potential biomarkers related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic.
  
  
  RESULTS
  Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods was integrated to examine the cerebral metabolic signature of human α-synuclein transgenic mice and the effects of AS on central nervous system (CNS) in pathology and physiology. Totally, 17 differentially expressed metabolites in wild type (WT) group and 26 in A30P mutant (A30P) group were identified and considered as potential biomarkers. Among them, 11 endogenous metabolites in WT+AS group and 18 in A30P+AS group were involved in the anti-α-synucleinopathies mechanism of AS. However, western blot and metabolomics analysis showed the effects of AS on CNS in physiology were opposite to those in pathology, which may cause potential neurotoxicity.
  
  
  CONCLUSIONS
  This study demonstrated that endogenous metabolites perturbation was involved in the pathogenesis of α-synucleinopathies and AS produced the dual effects on pathological and physiological CNS.
authors: Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China.
authors: Shuai-Nan
authors: SN
authors: Zhang
authors: Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China.
authors: Xu-Zhao
authors: XZ
authors: Li
authors: Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China. Electronic address: lufang_19790501@163.com.
authors: Fang
authors: F
authors: Lu
authors: Chinese Medicine Toxicological Laboratory, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China; Drug Safety Evaluation Center, Heilongjiang University of Chinese Medicine, Harbin 150040, PR China. Electronic address: keji-liu@163.com.
authors: Shu-Min
authors: SM
authors: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D028001:Eleutherococcus; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D010936:Plant Extracts; C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Acanthopanax senticosus Harms; Neurodegeneration; Parkinson׳s disease; Potential biomarkers; UPLC-QTOF-MS; α-synuclein