Zong Nan, Li Fei, Deng Yuanyuan, Shi Jingshan, Jin Feng, Gong Qihai
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Guizhou 563000, China.
Behav Brain Res. 2016 Oct 15;313:111-119. doi: 10.1016/j.bbr.2016.06.055. Epub 2016 Jun 28.
Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD.
兴奋性毒性是神经元死亡研究最为广泛的原因之一，在阿尔茨海默病（AD）中起重要作用。淫羊藿苷是一种传统中药的黄酮类成分，据报道具有广泛的药理作用。本研究旨在探讨淫羊藿苷对兴奋性毒性诱导的学习记忆障碍的影响。在此，我们证明，接受脑室内注射兴奋性神经毒素鹅膏蕈氨酸的大鼠表现出学习记忆障碍。以20和40mg/kg剂量口服淫羊藿苷可挽救行为表现，并通过抑制鹅膏蕈氨酸诱导的促凋亡作用保护大鼠海马免受神经毒性。此外，海马标本的蛋白质免疫印迹分析显示，给予鹅膏蕈氨酸后，淫羊藿苷上调了钙结合蛋白-D28k的表达。此外，淫羊藿苷抑制丝裂原活化蛋白激酶（MAPK）家族磷酸化和核因子κB（NF-κB）信号传导，这表明MAPK信号传导和NF-κB信号传导途径参与了淫羊藿苷介导的针对鹅膏蕈氨酸诱导的兴奋性毒性的神经保护机制。这些数据表明，淫羊藿苷可能是治疗包括AD在内的兴奋性毒性相关疾病的潜在药物。
