Peoniflorin attentuates Abeta((1-42))-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats.
Peoniflorin (PEF), a monoterpene glycoside isolated from the aqueous extract of the dry root of Paeonia, possesses wide pharmacological effects in nervous system. In this study, by using a developed rat model of hippocampal dysfunction induced by intrahippocampal injection of Abeta((1-42)) oligomers, we investigated whether PEF exerted protection against Abeta-induced neurotoxicity. A stereotactic intrahippocampal bilateral injection of Abeta((1-42)) (5 microg per side) was performed in Sprague-Dawley rats (250-280 g). Abeta((1-42))-exposed rats showed remarkable memory impairment in Morris water maze test and neuronal apoptosis by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in hippocampus. Chronic treatment with PEF (7.5, 15 and 30 mg/(kg day), for 20 days, intraperitoneally) significantly and dose-dependently attenuated cognitive deficit, ameliorated cell apoptosis in Abeta((1-42))-treated rats. The neuroprotective effect of PEF was closely associated with its activities of maintenance of [Ca(2+)](i) homeostasis, increase of reduced glutathione (GSH) content, suppression of NOS activity and nitric oxide (NO) level, decrease of carbonyl protein (CP) and malondialdehyde (MDA) levels. These results suggested that PEF possessed the activity of prevention of the neurotoxicity induced by Abeta((1-42)) and might exert beneficial action for the treatment of Alzheimer's disease (AD).
Zhong
Shu-Zhi
SZ
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, PR China.
Ge
Qing-Hua
QH
Li
Qiao
Q
Qu
Rong
R
Ma
Shi-Ping
SP
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology; D039821:Monoterpenes; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D050050:Protein Carbonylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D006027:Glycosides
D016229:Amyloid beta-Peptides; D001565:Benzoates; D001952:Bridged-Ring Compounds; D002118:Calcium; D005960:Glucosides; D005978:Glutathione; D008315:Malondialdehyde; D039821:Monoterpenes; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C015423:peoniflorin; D006027:Glycosides