(-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury

J Neurosci Res. 2004 Dec 1;78(5):723-31. doi: 10.1002/jnr.20315.

Abstract

Microglial activation is believed to play a pivotal role in the selective neuronal injury associated with several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. We provide evidence that (-)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, potently inhibits lipopolysaccharide (LPS)-activated microglial secretion of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) through the down-regulation of inducible NO synthase and TNF-alpha expression. In addition, EGCG exerted significant protection against microglial activation-induced neuronal injury both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. Our study demonstrates that EGCG is a potent inhibitor of microglial activation and thus is a useful candidate for a therapeutic approach to alleviating microglia-mediated dopaminergic neuronal injury in PD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Blotting, Western / methods
  • Carbocyanines
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology*
  • Catechin / therapeutic use
  • Cell Count / methods
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay / methods
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Lipopolysaccharides / pharmacology
  • Microglia / drug effects*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Neuroblastoma
  • Neurons / drug effects*
  • Nitric Oxide / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • 3,3'-dihexadecylindocarbocyanine
  • Antioxidants
  • Carbocyanines
  • Culture Media, Conditioned
  • Lipopolysaccharides
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Catechin
  • epigallocatechin gallate
  • Tyrosine 3-Monooxygenase
  • thiazolyl blue
  • Dopamine