In recent years, with the in-depth understanding of the pathogenesis of Alzheimer's disease (AD) and the development of advanced pharmacological technology, "multi-target" strategy has recently attracted the wide interest of scientists. The purpose of this study was to investigate the protective effect and mechanism of bulbocodin D for AD in vitro. In this study, we established the oxidative stress model of SH-SY5Y cells mediated by H₂O₂ and the inflammatory model of BV2 cells stimulated by LPS. Western blot was used to analysis the expression of mitochondrial apoptosis and inflammation related proteins. Moreover, predicted binding modes of bulbocodin D with AChE and GSK3β were performed by molecular docking analysis. We found that bulbocodin D could reduce cell apoptosis, reduce ROS production in SH-SY5Y cell, and inhibit the secretion of inflammatory cytokines in BV2 cell. Furthermore, western blot results showed that bulbocodin D could regulate mitochondrial apoptotic pathway and MAPKs pathway. In addition, bulbocodin D can reduce the aggregation of Aβ. We also found that bulbocodin D had a good inhibitory effect on AChE and GSK3β. In summary, bulbocodin D might be a potential multi-target agent for Alzheimer’s disease.

近年来，随着对阿尔茨海默病（AD）发病机制的深入了解和先进药理技术的发展，“多靶点”策略近来引起了科学家们的广泛兴趣。本研究的目的是研究bulbocodin D在体外对AD的保护作用和机制。本研究建立了H ₂ O ₂介导的SH-SY5Y细胞氧化应激模型。LPS 刺激 BV2 细胞的炎症模型。Western blot分析线粒体凋亡和炎症相关蛋白的表达。此外，通过分子对接分析进行了bulbocodin D与AChE和GSK3β的预测结合模式。我们发现bulbocodin D可以减少细胞凋亡，减少SH-SY5Y细胞中ROS的产生，并抑制BV2细胞中炎性细胞因子的分泌。此外，蛋白质印迹结果显示bulbocodin D可以调节线粒体凋亡途径和MAPKs途径。此外，bulbocodin D 可以减少 Aβ 的聚集。我们还发现bulbocodin D对AChE和GSK3β具有良好的抑制作用。总之，bulbocodin D 可能是阿尔茨海默病的潜在多靶点药物。