Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson's disease

Biochim Biophys Acta. 2016 Oct;1862(10):1883-90. doi: 10.1016/j.bbadis.2016.07.008. Epub 2016 Jul 15.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5mg/kg, 12weeks). Baicalein (100mg/kg) was intraperitoneally injected from 7week to 12week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.

Keywords: Baicalein; Flavonoid; Neurodegenerative disease; Parkinson's disease; Rotenone; α-Synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Flavanones / pharmacology*
  • Male
  • Mesencephalon / metabolism*
  • Mesencephalon / pathology
  • Mice
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism*
  • Parkinson Disease, Secondary / pathology
  • Protein Multimerization / drug effects*
  • Rotenone / adverse effects*
  • Rotenone / pharmacology
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • alpha-Synuclein / metabolism*

Substances

  • Flavanones
  • Snca protein, mouse
  • alpha-Synuclein
  • Rotenone
  • baicalein