Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats.
Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats.
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DOI：
10.3389/fphar.2017.00039
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发表时间：
2017
影响因子：
5.6
通讯作者：
Gong Q
中科院分区：
文献类型：
--
作者：
Deng Y;Long L;Wang K;Zhou J;Zeng L;He L;Gong Q
β-淀粉样蛋白（Aβ）沉积、相关的神经元凋亡和神经炎症被认为是导致阿尔茨海默病（AD）认知功能障碍的重要因素。淫羊藿苷II（Icariside II，ICS II）是从淫羊藿（Epimedium brevicornum Maxim）中提取的一种黄酮类化合物，在中医药中被广泛用于治疗勃起功能障碍、骨质疏松症和痴呆症。近年来，ICS II因其广谱抗癌特性而引起人们极大的兴趣。ICS II在癌症治疗和脑缺血再灌注中均显示出抗炎潜力。目前尚不清楚ICS II的抗炎作用是否可以延缓AD的进展。因此，本研究旨在研究ICS II对Aβ25-35处理大鼠的行为缺陷、Aβ水平、神经炎症反应和细胞凋亡的影响。结果发现，双侧海马注射Aβ25-35可引起大鼠认知功能障碍、神经元损伤，并伴随沿着Aβ的增加，海马出现炎症反应和凋亡。然而，ICS II 20 mg/kg治疗可改善认知缺陷，改善神经元死亡，并降低海马中的Aβ水平。ICS Ⅱ还能抑制小胶质细胞和星形胶质细胞的活化，抑制IL-1β、TNF-α、考克斯-2和iNOS mRNA和蛋白的表达，减轻Aβ诱导的Bax/Bcl-2比值升高和caspase-3活化。总之，这些结果表明ICS II可以逆转Aβ诱导的认知缺陷，可能通过抑制神经炎症和细胞凋亡，这表明ICS II对AD具有潜在的保护作用。
Beta-amyloid (Aβ) deposition, associated neuronal apoptosis and neuroinflammation are considered as the important factors which lead to cognitive deficits in Alzheimer’s disease (AD). Icariside II (ICS II), an active flavonoid compound derived from Epimedium brevicornum Maxim, has been extensively used to treat erectile dysfunction, osteoporosis and dementia in traditional Chinese medicine. Recently, ICS II attracts great interest due to its broad-spectrum anti-cancer property. ICS II shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion. It is not yet clear whether the anti-inflammatory effect of ICS II could delay progression of AD. Therefore, the current study aimed to investigate the effects of ICS II on the behavioral deficits, Aβ levels, neuroinflammatory responses and apoptosis in Aβ25-35-treated rats. We found that bilateral hippocampal injection of Aβ25-35 induced cognitive impairment, neuronal damage, along with increase of Aβ, inflammation and apoptosis in hippocampus of rats. However, treatment with ICS II 20 mg/kg could improve the cognitive deficits, ameliorate neuronal death, and reduce the levels of Aβ in the hippocampus. Furthermore, ICS II could suppress microglial and astrocytic activation, inhibit expression of IL-1β, TNF-α, COX-2, and iNOS mRNA and protein, and attenuate the Aβ induced Bax/Bcl-2 ratio elevation and caspase-3 activation. In conclusion, these results showed that ICS II could reverse Aβ-induced cognitive deficits, possibly via the inhibition of neuroinflammation and apoptosis, which suggested a potential protective effect of ICS II on AD.