ICARISIDE II, A NOVEL PHOSPHODIESTERASE-5 INHIBITOR, ATTENUATES STREPTOZOTOCIN-INDUCED COGNITIVE DEFICITS IN RATS
ICARISIDE II, A NOVEL PHOSPHODIESTERASE-5 INHIBITOR, ATTENUATES STREPTOZOTOCIN-INDUCED COGNITIVE DEFICITS IN RATS
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Icariside II 是一种新型磷酸二酯酶 5 抑制剂，可减轻链脲佐菌素诱导的大鼠认知缺陷。
DOI：
10.1016/j.neuroscience.2016.04.022
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发表时间：
2016-07-22
期刊：
影响因子：
3.3
通讯作者：
Gong, Qihai
中科院分区：
文献类型：
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作者：
Yin, Caixia;Deng, Yuanyuan;Gong, Qihai
β-淀粉样蛋白(Aβ)沉积和神经炎症与阿尔茨海默病(AD)型神经退行性变伴认知缺陷有关。磷酸二酯酶-5(PDE5)抑制剂最近被研究为通过减少炎症反应和Aβ水平来增强认知的潜在靶点。本研究旨在观察淫羊藿苷II(ICS II)对侧脑室注射链脲佐菌素(ICV-STZ)所致大鼠认知功能障碍、Aβ水平及神经炎症的影响。结果表明，ICV-STZ大鼠海马区存在认知功能障碍和神经元形态损害，同时伴有Aβ升高和神经炎症反应。ICS II可改善STZ大鼠的认知障碍，减轻神经元死亡，降低海马区Aβ(1-40)、Aβ(1-42)和PDE5的水平。ICS II以10 mg/kg剂量连续给药21d，可显著抑制β-淀粉样前体蛋白(APP)、β-分泌酶1(BACE1)的表达，增加Neprilysin(NEP)的表达，同时抑制IL-1β、肿瘤坏死因子(TNF)-α、环氧合酶-2(COX-2)和转化生长因子-β1(TGF-β1)的水平。ICS II对STZ诱导的I-kappa B-α降解和核因子-kappaB活化均有抑制作用。综上所述，本研究表明ICS II是一种潜在的治疗AD的药物。(C)2016年IBRO。爱思唯尔有限公司出版。保留所有权利。
Beta-amyloid (A beta) deposition and neuroinflammation are involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and A beta levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive deficits, A beta levels and neuroinflammation induced by intracerebroventricular-streptozotocin (ICV-STZ) in rats. The results demonstrated that ICV-STZ exhibited cognitive deficits and neuronal morphological damage, along with A beta increase and neuroinflammation in the rat hippocampus. ICS II improved cognitive deficits, attenuated neuronal death, and decreased the levels of A beta(1-40), A beta(1-42) and PDE5 in the hippocampus of STZ rats. Furthermore, administration of ICS II at the dose of 10 mg/kg for 21 days significantly suppressed the expression of beta-amyloid precursor protein (APP), beta-secretase1 (BACE1) and increased the expressions of neprilysin (NEP) together with inhibited interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF)-alpha, cyclooxygenase-2 (COX-2) and transforming growth factor-beta 1 (TGF-beta 1) levels. In addition, ICS II exerted a beneficial effect on inhibition of I kappa B-alpha degradation and NF-kappa B activation induced by STZ. Taken together, the present study demonstrated that ICS II was a potential therapeutic agent for AD treatment. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.