Hebei University of Chinese Medicine, Hebei Key Laboratory of Chinese Medicine Research On Cardio-cerebrovasc, Hebei, Shijiazhuang, 050091, China.
Hebei University of Chinese Medicine, Hebei Key Laboratory of Chinese Medicine Research On Cardio-cerebrovasc, Hebei, Shijiazhuang, 050091, China.
Neurochem Int. 2024 May;175:105705. doi: 10.1016/j.neuint.2024.105705. Epub 2024 Feb 25.
Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the quality of life of the elderly. Its pathogenesis has not yet been fully elucidated. Ferroptosis, a cell death caused by excessive accumulation of iron-dependent lipid peroxides, has been implicated in the pathogenesis of AD. Uncontrolled lipid peroxidation is the core process of ferroptosis, and inhibiting lipid peroxidation of ferroptosis may be an important therapeutic target for AD. Based on previous studies, we mixed standards of icariin, astragaloside IV, and puerarin, named the standard mixture YHG, and investigated the effect of YHG on ferroptosis -lipid peroxidation in APP/PS1 mice. DFX, a ferroptosis inhibitor, was used as a control drug. In this study, APP/PS1 mice were used as an AD animal model, and behavioral experiments, iron level detection, Transmission electron microscopy (TEM) observation, lipid peroxidation level detection, antioxidant capacity detection, immunofluorescence, Western blot and real-time qPCR were performed. It was found that YHG could reduce body weight, significantly improve abnormal behaviors and the ultrastructure of hippocampal neurons in APP/PS1 mice. The results of biochemical tests showed that YHG reduced the contents of iron, malondialdehyde (MDA) and lipid peroxide (LPO) in brain tissue and serum, and increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Immunofluorescence, WesternBlot and real-time qPCR results showed that YHG could promote the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4(GPX4). Inhibited the expression of long-chain acyllipid coenzyme a synthetase 4(ACSL4) and lysophosphatidyltransferase 3 (LPCAT3). This study suggests that the mechanism by which YHG improves cognitive dysfunction in APP/PS1 mice may be related to the inhibition of ferroptosis-lipid peroxidation.
阿尔茨海默病（AD）是一种严重威胁老年人生活质量的神经退行性疾病。其发病机制尚未完全阐明。铁死亡是一种由铁依赖性脂质过氧化物过度积累引起的细胞死亡，与 AD 的发病机制有关。不受控制的脂质过氧化是铁死亡的核心过程，抑制铁死亡的脂质过氧化可能是 AD 的重要治疗靶点。基于以往的研究，我们混合了淫羊藿苷、黄芪甲苷和葛根素的标准，命名为标准混合物 YHG，并研究了 YHG 对 APP/PS1 小鼠铁死亡-脂质过氧化的影响。DFX，一种铁死亡抑制剂，作为对照药物。在这项研究中，我们使用 APP/PS1 小鼠作为 AD 动物模型，进行行为实验、铁水平检测、透射电子显微镜（TEM）观察、脂质过氧化水平检测、抗氧化能力检测、免疫荧光、Western blot 和实时 qPCR。结果发现，YHG 可降低 APP/PS1 小鼠的体重，显著改善其异常行为和海马神经元的超微结构。生化测试结果表明，YHG 降低了脑组织和血清中铁、丙二醛（MDA）和脂质过氧化物（LPO）的含量，增加了超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）的水平。免疫荧光、Western blot 和实时 qPCR 结果表明，YHG 可促进溶质载体家族 7 成员 11（SLC7A11）、溶质载体家族 3 成员 2（SLC3A2）和谷胱甘肽过氧化物酶 4（GPX4）的表达。抑制长链酰基辅酶 A 合成酶 4（ACSL4）和溶血磷脂酰转移酶 3（LPCAT3）的表达。本研究表明，YHG 改善 APP/PS1 小鼠认知功能障碍的机制可能与抑制铁死亡-脂质过氧化有关。
