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Protective effect of I lex latifolia on $A{\beta}$ (25-35)-induced memory impairment via antiapoptotic and anti-acetylcholinesterase activities

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201 -P3-18

Protective effect of I lex latifolia on Aβ (25-35)-induced memory impairment via antiapoptotic and anti-acetylcholinesterase activities

Ji Yeon Jang and Yeon Hee Seong

College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea

실험목적 (Objectives)

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and progressive memory loss. Amyloid β protein (Aβ) or Aβ peptide fragments have been suggested to play an important role in the pathogenesis of AD. Acetylcholine plays a crucial role in memory, learning, and movement. Perturbed cholinergic transmission is involved in devastating disorders in AD. Ilex latifolia

(Aquifoliaceae) has been traditionally used in China to treat various kinds of inflammatory diseases and headaches. A previous study demonstrated neuroprotection of I.latifolia against ischemia-induced brain damages in rats. The aim of the present study is to investigate the neuroprotective effects of the ethanol extract of I.latifolia

against amyloid β protein (Aβ)-induced memory impairment in mice and neurotoxicity in cultured rat cortical neurons.

재료 및 방법 (Materials and Methods)

Memory impairment in mice was induced by intracerebroventricular injection of Aβ (25-35) (15nmol). A passive avoidance test and the Morris-water maze test were used to test for memory. Glutathione (GSH) concentration, lipid peroxidation rate and acetylcholinesterase (AChE) activity were measured in memory-impaired mice brains. The expression levels of phosphorylated tau protein (p-tau) and pro-apoptotic proteins in the brain tissues were detected by western blotting. Protective effect of I .latifolia

against 10 μM Aβ(25-35)-induced neuronal cell death, elevation of intacellular Ca2+ concentration ([Ca2+]

i), generation of reactive oxygen species (ROS), and expressions

of pro-apoptotic proteins were measured in primarily cultured cortical neurons. 실험결과 (Results)

Chronic administration of I. latifolia (25-100 mg/kg, p.o.) significantly prevented Aβ (25-35)-induced memory loss, decrease of GSH concentration, and increase of lipid peroxidation, AChE activity, and the expressions of p-tau and pro-apoptotic proteins in the brains of mice. Aβ (25-35)-induced neuronal cell death, elevation of [Ca2+]i,

generation of ROS and expressions of pro-apoptotic proteins were also inhibited by 주저자 연락처 (Corresponding author) : 성연희 E-mail : [email protected] Tel : 043-261-2968

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202

-the treatment with I. latifolia (1-50 μg/ml) in cultured neurons. These results suggest that I. latifolia may have a possible therapeutic role to manage cognitive impairment, associated with Alzheimer’s disease. This is through anti-apoptotic activity mediated by anti-oxidant activity and inhibition of p-tau formation, and through anti-AChE activity.

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