Neuroprotective effect of epigallocatechin-3-gallate against β-amyloid-induced oxidative and nitrosative cell death via augmentation of antioxidant defense capacity

• Published in: Archives of pharmacal research Vol. 32; no. 6; pp. 869 - 881
• Main Authors: Kim, Chang-Yul, Lee, Chan, Park, Gyu Hwan, Jang, Jung-Hee
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.06.2009; 대한약학회
• Subjects: Amyloid beta-Peptides - antagonists & inhibitors; Animals; Antioxidants - metabolism; Apoptosis - drug effects; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Death - drug effects; Cell Line; Glutamate-Cysteine Ligase - metabolism; Glutathione - metabolism; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medicine; Microglia - drug effects; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Sprague-Dawley; Reactive Nitrogen Species - antagonists & inhibitors; Reactive Oxygen Species - antagonists & inhibitors; 약학; γ-Glutamylcysteine ligase; Oxidative and nitrosative stress; Alzheimer’s disease; Epigallocatechin-3-gallate; β-Amyloid; Apoptosis; Glutathione
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-009-1609-z

β-Amyloid (Aβ) peptide, a major component of senile plaques has been regarded to play a crucial role in the development and neuropathogenesis of Alzheimer’s disease (AD). Increasing data from in vitro and in vivo studies indicate that Aβ-induced damages in neurons and glia are mediated via nitrosative as well as oxidative stress. Therefore, recent researches have been focused on searching for dietary and herbal manipulations to protect against the Aβ-induced oxidative and/or nitrosative cell death. Epigallocatechin-3-gallate (EGCG), one of these candidates is a major polyphenolic compound present in green tea and has been reported to exhibit potent antioxidant and anti-inflammatory properties. In the present study, we have investigated the effect of EGCG against Aβ-induced oxidative and/or nitrosative cell death in BV2 microglia. Aβ treatment led to apoptosis in BV2 cells as revealed by DNA fragmentation, perturbation of mitochondrial transmembrane potential, and alterations in the expression of apoptosis-regulator Bcl-2 family proteins. EGCG pretreatment effectively ameliorated Aβ-induced cytotoxicity and manifestation of proapoptotic signals. Furthermore, BV2 cells exposed to Aβ underwent nitrosative stress as shown by the increased expression of inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO) and peroxynitrite, which were effectively suppressed by EGCG pretreatment. To elucidate a molecular mechanism underlying the neuroprotective effect of EGCG, we have examined the cellular metabolism of reduced glutathione (GSH) with antioxidant properties. EGCG treatment fortified cellular GSH pool through elevated mRNA expression of γ-glutamylcysteine ligase (GCL), the rate limiting enzyme in the glutathione biosynthesis. These results suggest that EGCG may have preventive and/or therapeutic potential in AD patients by augmenting cellular antioxidant defense capacity and attenuating Aβ-mediated oxidative and/or nitrosative cell death.