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Discovery of novel anti-parkinsonian effect of schisantherin A in in vitro and in vivo.

Abstract
Dibenzocyclooctadiene lignans represent a unique group of natural chemical structures, are considered as protectants against neuronal cell death and cognitive impairment in neurological disorders. Among the family of dibenzocyclooctadiene lignan analogs from the fruit of Schisandra chinensis (Turcz.) Baill, neuroprotective potential of schisantherin A (StA) has not yet been characterized. In this study, 1-methyl-4-phenylpyridinium ion (MPP(+))-incubated SH-SY5Y cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to study the neuroprotection of StA. Pretreatment with StA significantly inhibited MPP(+)-induced cytotoxicity in SH-SY5Y cells. Moreover, StA conferred significant protection against MPTP-induced loss of TH-positive dopaminergic neurons in a Parkinson's disease (PD) mice model. Structure activity relationship analysis suggested that methylenedioxy, benzoyloxy and methoxyl groups, in the dibenzocyclooctadiene lignan of StA, were probably functionally important to its neuroprotective activity. In addition, Western blotting analysis demonstrated that StA exhibited neuroprotection against MPP(+) through the regulation of two distinct pathways including increasing CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signaling suggesting that StA might be a promising neuroprotective agent for the prevention of PD.
AuthorsFei Sa, Lun Qing Zhang, Cheong Meng Chong, Bao Jian Guo, Sai Li, Zai Jun Zhang, Ying Zheng, Pui Man Hoi, Simon Ming Yuen Lee
JournalNeuroscience letters (Neurosci Lett) Vol. 593 Pg. 7-12 (Apr 23 2015) ISSN: 1872-7972 [Electronic] Ireland
PMID25770828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Antiparkinson Agents
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Cyclooctanes
  • Dioxoles
  • Lignans
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • schizandrer A
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • 1-Methyl-4-phenylpyridinium
Topics
  • 1-Methyl-4-phenylpyridinium
  • Animals
  • Antiparkinson Agents (pharmacology)
  • Brain (drug effects, pathology)
  • Cell Line, Tumor
  • Cell Survival
  • Cyclic AMP Response Element-Binding Protein (metabolism)
  • Cyclooctanes (pharmacology)
  • Dioxoles (pharmacology)
  • Dopaminergic Neurons (drug effects, pathology)
  • Humans
  • Lignans (pharmacology)
  • Male
  • Mice, Inbred C57BL
  • Neuroprotective Agents (pharmacology)
  • Parkinson Disease (drug therapy, etiology, pathology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • Signal Transduction

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