A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2.
The aim of the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO(2)). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO(2) (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO(2) injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO(2) induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO(2), indicating that FLZ is worth further studies for fighting antisenescence and dementia.
Fang
Fang
F
Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Liu
Gengtao
G
D000284:Administration, Oral; D000375:Aging / Q000187:drug effects; D000818:Animals; D031041:Annona / Q000737:chemistry*; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D003704:Dementia / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005690:Galactose; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D008853:Microscopy; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D012977:Sodium Nitrite; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D044482:Benzeneacetamides; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; C084439:squamosamide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D012977:Sodium Nitrite; D005690:Galactose