Biological evaluation of naturally occurring bulbocodin D as a potential multi-target agent for Alzheimer's disease

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.