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A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2.
Basic Clin Pharmacol Toxicol. 2007 Dec; 101(6):447-54.BC

Abstract

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.

Authors+Show Affiliations

Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17971066

Citation

Fang, Fang, and Gengtao Liu. "A Novel Cyclic Squamosamide Analogue Compound FLZ Improves Memory Impairment in Artificial Senescence Mice Induced By Chronic Injection of D-galactose and NaNO2." Basic & Clinical Pharmacology & Toxicology, vol. 101, no. 6, 2007, pp. 447-54.
Fang F, Liu G. A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. Basic Clin Pharmacol Toxicol. 2007;101(6):447-54.
Fang, F., & Liu, G. (2007). A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. Basic & Clinical Pharmacology & Toxicology, 101(6), 447-54.
Fang F, Liu G. A Novel Cyclic Squamosamide Analogue Compound FLZ Improves Memory Impairment in Artificial Senescence Mice Induced By Chronic Injection of D-galactose and NaNO2. Basic Clin Pharmacol Toxicol. 2007;101(6):447-54. PubMed PMID: 17971066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. AU - Fang,Fang, AU - Liu,Gengtao, Y1 - 2007/10/25/ PY - 2007/11/1/pubmed PY - 2008/1/30/medline PY - 2007/11/1/entrez SP - 447 EP - 54 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin Pharmacol Toxicol VL - 101 IS - 6 N2 - 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. SN - 1742-7843 UR - https://www.unboundmedicine.com/medline/citation/17971066/A_novel_cyclic_squamosamide_analogue_compound_FLZ_improves_memory_impairment_in_artificial_senescence_mice_induced_by_chronic_injection_of_D_galactose_and_NaNO2_ L2 - https://doi.org/10.1111/j.1742-7843.2007.00138.x DB - PRIME DP - Unbound Medicine ER -