title: Neuroprotective effects of (-)-epigallocatechin-3-gallate on aging mice induced by D-galactose.
abstract: The aim of the present study was to investigate the protective effects of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, in aging mice induced by D-galactose (D-gal). The aging mice model was induced by subcutaneous (s.c.) injection of D-gal (150 mg/kg) once daily for 6 weeks. EGCG (2 mg/kg or 6 mg/kg) was administered intragastrically (i.g.) once daily for 4 weeks after 2-week D-gal injection. The water maze test was used to evaluate the learning and memory function of mice. The activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) in the hippocampus were measured using different biochemical kits to estimate the changes in the antioxidative ability of mice. TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining method was used to detect neuronal apoptosis, and the activation and expression of proapoptotic protein caspase-3 in the hippocampus were observed and analyzed using immunohistochemical staining and the Western blot method to evaluate apoptosis in the brain. The results indicated that subcutaneous injection of D-gal induced learning and memory impairment in mice, decreased T-SOD and GSH-Px activities, increased MDA contents in the hippocampus, and increased the cell apoptosis index and cleaved caspase-3 protein expression in the hippocampus. Oral administration of EGCG (2 mg/kg or 6 mg/kg) for 4 weeks significantly improved the cognitive deficits in mice and elevated T-SOD and GSH-Px activities, decreased MDA contents in the hippocampus, and reduced the cell apoptosis index and expression of cleaved caspase-3 in the mouse hippocampus. The results suggest that EGCG has potent neuroprotective effects on aging mice induced by D-gal through antioxidative and antiapoptotic mechanisms, indicating that EGCG is worthy of further study in aging.
authors.affiliation: Department of Pharmacology, Pharmaceutical College of China Medical University, Liaoning Province, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Wei
authors.forename: Wei-Fan
authors.initials: WF
authors.lastname: Yao
authors.forename: Hai-Shan
authors.initials: HS
authors.lastname: Zhao
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005690:Galactose / Q000009:adverse effects*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D008315:Malondialdehyde; D002392:Catechin; C045651:epigallocatechin gallate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005690:Galactose