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