Abstract：
Polygala tenuifolia was documented to calm the mind and promote wisdom. However, its underlying mechanisms are still unclear. This study aimed to investigate the mechanisms underlying the effects of tenuifolin (Ten) on Alzheimer\'s disease (AD)-like phenotypes. We first applied bioinformatics methods to screen the mechanisms of P. tenuifolia in the treatment of AD. Thereafter, the d-galactose combined with Aβ1-42 (GCA) was applied to model AD-like behaviors and investigate the action mechanisms of Ten, one active component of P. tenuifolia. The data showed that P. tenuifolia actioned through multi-targets and multi-pathways, including regulation of synaptic plasticity, apoptosis, and calcium signaling, and so forth. Furthermore, in vitro experiments demonstrated that Ten prevented intracellular calcium overload, abnormal calpain system, and down-regulation of BDNF/TrkB signaling induced by GCA. Moreover, Ten suppressed oxidative stress and ferroptosis in HT-22 cells induced by GCA. Calpeptin and ferroptosis inhibitor prevented the decrease of cell viability induced by GCA. Interestingly, calpeptin did not interrupt GCA-induced ferroptosis in HT-22 cells but blocked the apoptosis. Animal experiments further demonstrated that Ten prevented GCA-induced memory impairment in mice and increased synaptic protein expression while reducing m-calpain expression. Ten prevents AD-like phenotypes through multiple signaling by inhibiting oxidative stress and ferroptosis, maintaining the stability of calpain system, and suppressing neuronal apoptosis.
摘要：
远志被证明可以镇静思想并促进智慧。然而,其潜在机制仍不清楚。本研究旨在探讨tenuifolin(十)对阿尔茨海默病(AD)样表型影响的潜在机制。我们首先应用生物信息学的方法来筛选黄芩在AD治疗中的作用机制。此后,将D-半乳糖联合Aβ1-42(GCA)用于模拟AD样行为,一种活性成分。数据表明，黄芩通过多靶点、多途径发挥作用，包括突触可塑性的调节，凋亡，和钙信号，等等。此外，体外实验表明，十能预防细胞内钙超载，异常的钙蛋白酶系统，以及GCA诱导的BDNF/TrkB信号的下调。此外，10个抑制GCA诱导的HT-22细胞的氧化应激和铁凋亡。钙肽和铁凋亡抑制剂可防止GCA诱导的细胞活力降低。有趣的是,钙肽不会中断GCA诱导的HT-22细胞的铁凋亡，但会阻止凋亡。动物实验进一步证明，十在小鼠中预防了GCA诱导的记忆障碍，并增加了突触蛋白的表达，同时降低了m-calpain的表达。十种通过抑制氧化应激和铁凋亡通过多种信号来预防AD样表型，维持钙蛋白酶系统的稳定，并抑制神经元凋亡。
