Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer’s disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication. We measured the concentration of Ca²⁺ ions in rat cortical tissue by inductively coupled plasma (ICP), the brain atrophy/curing and hydrocephalus by magnetic resonance imaging (MRI) besides light microscope histopathology. Our results revealed significant increase in synaptosomal membrane rgidification, order, lipid packing, reactive oxygen species (ROS) production and Ca²⁺ ion concentration as a result of Al intoxication. The dramatic increase in Ca²⁺ ion concentration detected in AD group associated with the increase in synaptic membrane polarity and EPR-detected order S-parameter suggest that release of synaptic vesicles into synaptic cleft might be hindered. LS treatment reversed these changes in synaptic membranes, and rescued an observed deficit in the exploratory behaviour of AD group. Our results also strongly suggest that the synaptosomal membrane phospholipids that underwent free radical attacks mediated by AlCl3, due to greater NOX activity, was prevented in the LS group. The results of ATR-IR and EPR spectroscopic techniques recommend LS as a promising therapeutic agent against synaptic membrane alterations opening a new window for AD drug developers.

突触体膜的过氧化和其生物物理特性的改变与铝（Al）毒性有关，可能导致认知功能障碍和阿尔茨海默氏病（AD），如发病机理。在这里，我们调查了作为一种天然抗炎剂，抗氧化剂和乙酰胆碱酯酶抑制剂治疗大鼠模型中的铝诱导的AD样的sa菜（LS）的治疗潜力。我们利用ATR-IR光谱技术追踪分离的大鼠皮质突触小体受损膜结构的恢复及其生物物理特性，电子顺磁共振（EPR）自旋俘获以跟踪NADPH氧化酶活性（NOX）和EPR自旋标记以响应LS Al中毒后的治疗。我们测量了Ca ²⁺的浓度除光显微镜组织病理学外，还通过感应耦合血浆（ICP），大脑萎缩/治愈和脑积水通过磁共振成像（MRI）清除大鼠皮质组织中的离子。我们的研究结果表明，由于铝中毒，滑膜的膜化，顺序，脂质堆积，活性氧（ROS）产生和Ca ²⁺离子浓度显着增加。Ca ²⁺急剧增加AD组中检测到的离子浓度与突触膜极性的增加和EPR检测到的S阶参数有关，提示可能会阻碍突触小泡释放到突触间隙中。LS治疗逆转了突触膜的这些变化，并挽救了AD组探索行为的观察到的缺陷。我们的研究结果也强烈表明，在LS组中，由于NOX活性较高而受到AlCl3介导的自由基攻击的突触体膜磷脂被预防。ATR-IR和EPR光谱技术的结果推荐LS作为抗突触膜改变的有前途的治疗剂，为AD药物开发人员打开了新的窗口。