Neuroprotective effects of 3-O-demethylswertipunicoside against MPTP-induced Parkinson's disease in vivo and its antioxidant properties in vitro

Brain Res. 2015 Oct 22:1624:78-85. doi: 10.1016/j.brainres.2015.06.051. Epub 2015 Jul 23.

Abstract

3-O-demethylswertipunicoside (3-ODS) has been reported to protect dopaminergic neurons against neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP(+)) in PC12 cells. Here, we investigate the neuroprotective effects in vivo and antioxidant activities in vitro of 3-ODS. In the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD), 3-ODS dose-dependently improved motor coordination (as shown by rotarod test), increased the contents of dopamine (DA) and its metabolites in the striatum, and increased the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN). In addition, 3-ODS also increased the spine density in hippocampal CA1 neurons. In antioxidant assays, 3-ODS showed a strong capacity in scavenging hydroxyl radical, superoxide anion and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical in a concentration-dependent manner. Taken together, we conclude that 3-ODS attenuates the PD-related motor deficits mainly through its neuroprotective effects, growth-promoting effects on spine density, and its antioxidant activities.

Keywords: 1-methyl-4-phenyl-1, 2, 3; 3-O-demethylswertipunicoside; 6-tetrahydropyridine; Antioxidant activity; Growth-promoting effect; Neuroprotection; Parkinson׳s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Biphenyl Compounds / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Glucosides / chemistry
  • Glucosides / therapeutic use*
  • Hippocampus / drug effects
  • Hydroxyl Radical / metabolism
  • In Vitro Techniques
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Picrates / metabolism
  • Spine / drug effects
  • Spine / pathology
  • Superoxides / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • Xanthones / chemistry
  • Xanthones / therapeutic use*

Substances

  • 3-O-demethylswertipunicoside
  • Biphenyl Compounds
  • Glucosides
  • Neuroprotective Agents
  • Picrates
  • Xanthones
  • 3,4-Dihydroxyphenylacetic Acid
  • Superoxides
  • Hydroxyl Radical
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1,1-diphenyl-2-picrylhydrazyl
  • Tyrosine 3-Monooxygenase
  • Dopamine