Phloroglucinol attenuates oligomeric amyloid beta peptide1-42-induced astrocytic activation by reducing oxidative stress

J Pharmacol Sci. 2021 Apr;145(4):308-312. doi: 10.1016/j.jphs.2021.01.008. Epub 2021 Jan 23.

Abstract

Astrocytes are the most abundant cell type in the central nervous system (CNS) and their major function is to maintain homeostasis of the CNS by exerting various functions. Simultaneously, reactive astrocytes are well known to be involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Reactive astrocytes, induced by amyloid beta peptide (Aβ), the main component of the neuritic plaques found in AD, induce neuroinflammation, producing cytokines that lead to neuronal cell death in AD. Phloroglucinol,a polyphenol monomer and a component of phlorotannin, is found at sufficient levels in Ecklonia cava of the Laminariaceae family. Recently, several studies have reported that phloroglucinol has the ability to trap free radicals in lung fibroblasts or cancer cells. However, the effects of phloroglucinol in astrocytes have not yet been studied. Here, we found that phloroglucinol inhibits the generation of ROS induced by oligomeric Aβ1-42 (oAβ1-42) treatment in primary astrocytes. Futhermore, phloroglucinol was shown to ameliorate the protein expression of glial fibrillary acidic protein, a marker of reactive astrocytes, after treatment with oAβ1-42. These results indicate that phloroglucinol exerts antioxidant effects in primary cultured astrocytes and attenuates the astrocytic activation induced by oAβ1-42.

Keywords: Alzheimer's disease; Oxidative stress; Phloroglucinol; Reactive astrocyte.

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / adverse effects*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Central Nervous System / cytology
  • Cytokines / metabolism
  • Free Radical Scavengers*
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Laminaria / chemistry
  • Mice
  • Oxidative Stress / drug effects*
  • Peptide Fragments / adverse effects*
  • Peptide Fragments / metabolism*
  • Phloroglucinol / isolation & purification
  • Phloroglucinol / pharmacology*
  • Reactive Oxygen Species / metabolism*

Substances

  • Amyloid beta-Peptides
  • Cytokines
  • Free Radical Scavengers
  • Glial Fibrillary Acidic Protein
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • Phloroglucinol