薯蓣皂苷元衍生物ML5激活NRF2信号通路改善AD的机制研究  

Mechanism of Diosgenin Derivative ML5 Activating NRF2 Signaling Pathway to Improve AD

作　　者：丁伟东 周宏磊 孙佳敏 马磊 王蕊 DING Weidong;ZHOU Honglei;SUN Jiamin;MA Lei;WANG Rui(Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学药学院,上海市新药设计重点实验室,上海200237

出　　处：《华东理工大学学报（自然科学版）》2024年第4期534-542,共9页Journal of East China University of Science and Technology

基　　金：国家自然科学基金(81973196);上海市自然科学基金(19ZR1413900)。

摘　　要：通过体外和体内实验研究了薯蓣皂苷元衍生物ML5的神经保护作用,并对其机制进行了探讨。结果表明,ML5可改善β淀粉样蛋白(Aβ)所致的小鼠学习和认知障碍,保护海马区神经元;ML5具有减轻过氧化氢(H_(2)O_(2))诱导的人神经母细胞瘤细胞(SH-SY5Y)损伤的功效,且提高三磷酸腺苷(ATP)和线粒体膜电位的水平;免疫印迹和免疫荧光结果显示,ML5可激活核因子红细胞系2相关因子2(NRF2)信号通路,增加NRF2、血红素加氧酶-1(HO-1)及NAD(P)H醌脱氢酶(NQO-1)的表达水平。ML5可能是一种治疗阿尔茨海默症(AD)的有效药物,通过靶向NRF2通路,进而发挥抗氧化和神经保护作用。Mitochondrial dysfunction and oxidative stress play a crucial role in the pathogenesis of Alzheimer’s disease(AD).The neuroprotective effects of the diosgenin derivative ML5 were investigated in vitro and in vivo,and the underlying mechanisms were explored.The results showed that ML5 ameliorated the study and cognitive deficits in beta-amyloid(Aβ_(1-42))-induced mouse model and protected neurons in the hippocampal region.In addition,ML5 attenuated H_(2)O_(2)-induced damage to SH-SY5Y cells and increased mitochondrial membrane potential and ATP levels.Western blot and immunofluorescence results showed that ML5 activated nuclear factor-erythroid-2-related factor 2(NRF2)signaling pathway and increased the expression of NRF2,heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase-1(NQO-1).Our findings suggest that ML5 may be used as a therapeutic drug for AD treatment via targeting the NRF2 pathway,thereby exerting antioxidant and neuroprotective effects.

关 键 词：阿尔茨海默症 薯蓣皂苷元 ML5 NRF2 神经保护 

分 类 号：R965[医药卫生—药理学]