去甲氧基姜黄素通过促进海马神经发生对阿尔兹海默症认知损伤的改善作用  

Effects of demethoxycurcumin on improving cognitive deficits due to Alzheimer’s disease via promotion of hippocampal neurogenesis

作　　者：林凯莉 张世卿[2] LIN Kai-li;ZHANG Shi-qing(School of Public Health,Guangzhou Medical University,Guangzhou 511436,China;Department of Biology,Hong Kong Baptist University,Kowloon Tong 999077,China)

机构地区：[1]广州医科大学公共卫生学院,广东广州511436 [2]香港浸会大学生物系,中国香港九龙塘999077

出　　处：《中成药》2022年第8期2476-2482,共7页Chinese Traditional Patent Medicine

基　　金：广州市基础与应用基础研究项目(202102020932)。

摘　　要：目的 探讨去甲氧基姜黄素通过促进海马神经发生治疗阿尔兹海默症的作用及机制。方法 体外实验以1.25、2.5、5.0μmol/L去甲氧基姜黄素干预原代培养神经干细胞(NSCs),采用CCK-8法检测NSCs增殖,Western blot法检测NSCs分化标志物(Nestin、MAP2)及GSK-3β/β-catenin通路蛋白表达。体内实验以2.5、5.0 mg/kg去甲氧基姜黄素干预APP/PS1转基因阿尔兹海默症小鼠模型,采用行为学实验检测小鼠认知能力,Nissl染色和免疫荧光染色评价海马神经发生水平,Western blot法检测海马组织中GSK3β/β-catenin通路蛋白表达。结果 体外实验显示,去甲氧基姜黄素促进NSCs增殖,促使其分化为神经元(P<0.05),并激活GSK-3β/β-catenin通路(P<0.05)。体内实验显示,去甲氧基姜黄素改善APP/PS1转基因小鼠的认知障碍(P<0.05),促进海马区神经发生(P<0.05),激活GSK-3β/β-catenin通路(P<0.05)。结论 去甲氧基姜黄素通过激活GSK-3β/β-catenin通路、促进海马神经发生来改善阿尔兹海默症的认知损伤。AIM To investigate the therapeutic effects and mechanisms of demethoxycurcumin on Alzheimer’s disease by enhancing hippocampal neurogenesis.METHODS The primary neural stem cells(NSCs) cultured with 1.25, 2.5 and 5.0 μmol/L demethoxycurcumin respectively in the in vitro study were subsequently subjected to the detection of their proliferation by CCK-8 method, and the investigation of expressions of Nestin, MAP2, the differentiation markers and GSK-3β/β-catenin pathway proteins by Western blot. APP/PS1 transgenic Alzheimer’s disease mouse models medicated with 2.5 and 5.0 mg/kg demethoxycurcumin respectively in the in vivo study were subsequently subjected to the test of their cognitive ability by behavioral experiments;the evaluation of the hippocampal neurogenesis level by Nissl staining and immunofluorescence staining;the determination of expressions of GSK3β/β-catenin pathway proteins in the hippocampal tissue by Western blot.RESULTS The effects of demethoxycurcumin in promoting the proliferation and differentiation of NSCs into neurons(P<0.05), and activating the GSK-3β/β-catenin pathway(P<0.05) were determined by the in vitro study. The effects of demethoxycurcumin in improving the cognitive deficits of APP/PS1 transgenic mice(P<0.05), promoting hippocampal neurogenesis(P<0.05), and activating the GSK-3β/β-catenin pathway(P<0.05) were verified by thein vivostudy.CONCLUSION Demethoxycurcumin improves the cognitive deficits due to Alzheimer’ s diseaseviapromoting hippocampal neurogenesis by activating the GSK-3β/β-catenin pathway.

关 键 词：去甲氧基姜黄素 阿尔兹海默症 神经干细胞 认知障碍 海马神经发生 

分 类 号：R285.5[医药卫生—中药学]