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

Ethnopharmacological relevance: 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. Aim of the study: Our pre-study has showed that AS can significantly suppress a-synuclein overexpression and toxicity. Neuronal protein a-synuclein is a key player in the development of neurodegenerative diseases called alpha-synucleinopathies. Identifying the potential biomarkers related to alpha-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Methods and 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 a-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-alpha-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 alpha-synucleinopathies and AS produced the dual effects on pathological and physiological CNS. (C) 2015 Elsevier Ireland Ltd. All rights reserved.