(-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury.
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.
Health Science Center, Shanghai Institute for Biological Science, Chinese Academy of Science, Shanghai Second Medical University, Shanghai, Peoples Republic of China.
Rui
R
Li
Yuan-Gui
YG
Huang
Du
D
Fang
Wei-Dong
WD
Le
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western / Q000379:methods; D002232:Carbocyanines; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C035005:3,3'-dihexadecylindocarbocyanine; D000975:Antioxidants; D002232:Carbocyanines; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D014446:Tyrosine 3-Monooxygenase; C022616:thiazolyl blue; D004298:Dopamine