title: FLZ, synthetic squamosamide cyclic derivative, attenuates memory deficit and pathological changes in mice with experimentally induced aging.
abstract: The aim of this study was to investigate the protective effects of N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (FLZ), a synthetic squamosamide cyclic derivative, on senescent mice induced by D: -galactose/NaNO(2) (120/90 mg/kg, i.p.) once daily for 60 days. FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D: -galactose/NaNO(2) treatment for 30 days. The cognitive function of mice was evaluated with step-down task. The brain biomarkers including monoamine oxidase B (MAO-B), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) were determined according to the manufacturer's instructions. The expression of acetylcholinesterase (ACh-E) and choline acetyltransferase (ChAT) protein in the CA1 region of hippocampus were counted by immunohistochemical staining. The results showed that the cognitive function, GSH-px activity in the brain, and the expression of ACh-E and ChAT in the CA1 region of hippocampus were significantly decreased, while MAO-B activity and MDA level in the brain were increased in senescent mice compared with the control mice. FLZ treatment prolonged the step-down latency and decreased the number of step-down errors in the senescent mice. In addition, FLZ treatment increased the GSH-px activity and the expression of ACh-E and ChAT in the hippocampus and decreased the MDA level and MAO-B activity compared with the senescent mice without drug administration. These findings suggested that FLZ improves the performance in the step-down task and the pathological alternations in senescent mice.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. fangf@bucm.edu.cn
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Qing-li
authors.initials: QL
authors.lastname: Wang
authors.forename: Geng-tao
authors.initials: GT
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D044482:Benzeneacetamides / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005690:Galactose; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D008995:Monoamine Oxidase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D012977:Sodium Nitrite
chemical_list: D044482:Benzeneacetamides; D018696:Neuroprotective Agents; D010636:Phenols; C084439:squamosamide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D008995:Monoamine Oxidase; D012977:Sodium Nitrite; D005690:Galactose