The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation

Brain Res Bull. 2017 Oct:135:47-52. doi: 10.1016/j.brainresbull.2017.09.007. Epub 2017 Sep 15.

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, and axonal pathology. Baicalein isolated from the roots of Scutellaria baicalensis has been shown to exert anti-inflammatory and antioxidant effects. The cuprizone model is an established mouse model of MS and causes demyelination and motor dysfunction and induces neuroinflammation, such as glial activation and pro-inflammatory cytokine production. To determine whether Baicalein attenuates cuprizone-induced demyelination, we administrated Baicalein to cuprizone-exposed mice. Baicalein attenuated weight loss (P<0.05) and motor dysfunction (P<0.05) in the cuprizone model mice. Baicalein treatment effectively suppressed the demyelination (P<0.01) and gene expressions of CNP (P<0.05) and MBP (P<0.05). Baicalein treatment also inhibited the cuprizone-induced increase in Iba1-positive microglia (P<0.001), GFAP-positive astrocytes (P<0.001), and the gene expressions of CD11b (P<0.01), GFAP (P<0.05), TNFα (P<0.05), IL-1β (P<0.05), and iNOS (p<0.01). We found that Baicalein treatment attenuated cuprizone-induced demyelination, glial activation, pro-inflammatory cytokine expression, and motor dysfunction. Our results suggest that Baicalein may be a useful therapeutic agent in demyelinating diseases to suppress neuroinflammation.

Keywords: Baicalein; Microglia; Multiple sclerosis; Myelin; Oligodendrocyte.

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Cuprizone / metabolism
  • Cuprizone / pharmacology
  • Cytokines / metabolism
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / drug therapy*
  • Disease Models, Animal
  • Flavanones / metabolism*
  • Flavanones / pharmacology
  • Flavonoids / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Multiple Sclerosis / drug therapy
  • Myelin Sheath / pathology
  • Neuroimmunomodulation / drug effects
  • Oligodendroglia / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Flavanones
  • Flavonoids
  • Tumor Necrosis Factor-alpha
  • baicalein
  • Cuprizone