Periplaneta americana (L.) extract alleviates the disease progression of Alzheimer's disease by inhibiting the expression of NMDAR in nerve cells

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. This study builds on the group's previous findings that Periplaneta americana (L.) extract (PAS840) provide protection against hydrogen peroxide-induced injury to PC12 cells. This study uses network pharmacology and molecular docking techniques to analyze the substance basis of PAS840 and predict its effects on AD targets. It then combines in vitro experiments to detect the effects of PAS840 on intracellular Ca2+ levels, cellular SOD, MDA, ROS levels, cell apoptosis rate, and MMP levels in Glutamic acid (Glu) injured cells. It also uses q-PCR and Western blot to detect the expression of NMDAR1, Cytc, Bcl-2, Bax, Caspase-3, TNF-α, and IL-6 in damaged cells. This study shows that PAS840 can act on multiple targets of AD and effectively reduce the activity of NMDAR receptors, resisting the excessive activation of NMDAR1 and preventing excessive intracellular Ca2+ influx, reducing cell damage, alleviating oxidative stress and inflammation, and improving cell viability, thereby achieving a therapeutic effect in slowing down the AD disease progression. This study provides a new therapeutic approach for the application of PAS840 in neurological disease treatment.阿尔茨海默病（Alzheimer's disease, AD）是最为常见的神经退行性疾病之一。本研究基于团队前期研究发现：美洲大蠊（Periplaneta americana (L.)）提取物（PAS840）可对抗过氧化氢诱导的PC12细胞损伤。本研究采用网络药理学与分子对接技术，分析PAS840的物质基础并预测其对AD靶点的调控作用；随后结合体外实验，检测PAS840对谷氨酸（Glutamic acid, Glu）损伤细胞内钙离子（Ca²+）水平、细胞超氧化物歧化酶（SOD）、丙二醛（MDA）、活性氧（ROS）水平、细胞凋亡率以及线粒体膜电位（Mitochondrial Membrane Potential, MMP）的影响；同时采用定量聚合酶链式反应（q-PCR）与蛋白质印迹法（Western blot）检测损伤细胞中NMDAR1、细胞色素C（Cytc）、B细胞淋巴瘤因子2（Bcl-2）、Bcl-2相关X蛋白（Bax）、半胱氨酸天冬氨酸蛋白酶3（Caspase-3）、肿瘤坏死因子α（TNF-α）以及白细胞介素6（IL-6）的表达水平。本研究结果显示，PAS840可作用于AD的多个靶点，有效降低NMDAR受体活性，拮抗NMDAR1的过度激活，阻断细胞内钙离子过量内流，减轻细胞损伤，缓解氧化应激与炎症反应，提升细胞活力，从而实现延缓AD疾病进展的治疗效果。本研究为PAS840在神经系统疾病治疗领域的应用提供了全新的治疗策略。