Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice.
The senescence-accelerated mouse prone 8 (SAMP8) is a novel aging model characterized by early onset and rapid advancement of senescence. In the present study, 6-month-old male SAMP8 mice were orally administered icariin (75, 150mg/kg) for 15weeks. Mice were submitted to passageway water maze test and step-down passive avoidance test for evaluating cognitive impairments. The HPLC-EC technique was used to determine the monoamine contents in the brain. The effects of icariin on oxidative stress and the acetylcholinesterase (AChE) activity of SAMP8 mice were also investigated. We found that icariin treatment significantly prevented learning and memory impairments of SAMP8 mice in passageway water maze test and step-down test. Icariin could partly reverse alterations of monoamines and metabolites levels in the cortex and hippocampus of SAMP8 mice. Furthermore, icariin-treated SAMP8 mice had significantly decreased malondialdehyde (MDA), nitric oxide (NO) contents, lowered nitric oxide synthase (NOS) activity and higher glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in the brain homogenates and serum. Meanwhile, the acetylcholinesterase activity was markedly inhibited after icariin administration. However, the positive control piracetam did not show significant beneficial effects. In conclusion, the present findings demonstrated that the improvement of icariin on cognitive impairments in SAMP8 mice may be due to increasing monoamines levels, inhibiting oxidative damage and decreasing acetylcholinesterase activity.
He
Xiao-Li
XL
Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Zhou
Wei-Qin
WQ
Bi
Ming-Gang
MG
Du
Guan-Hua
GH
D000110:Acetylcholinesterase / Q000378:metabolism; D000284:Administration, Oral; D000375:Aging / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000097:blood; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000097:blood; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009448:Neurochemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood
D005419:Flavonoids; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; C056599:icariin