Alzheimer’s disease (AD) is a common neurodegenerative disease with high incidence among old people. Dioscin is a product extracted from natural herbs, which has multiple pharmacological activities. In this study, we investigated the potential effects of disocin on amyloid-β peptide (Aβ1–42) oligomers-treated HT22 cells. Aβ1–42 oligomers induced great neurotoxicity to HT22 cells as examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results of terminal deoxynucleoitidyl transferase-mediated deoxyuridine triphosphate biotin nich end labeling (TUNEL) staining and flow cytometry indicated that Aβ1–42 oligomers led to increased apoptosis and generation of reactive oxygen species (ROS) in HT22 cells. However, dioscin could remarkably inhibit the neurotoxicity induced by Aβ1–42 oligomers, as well as decrease the apoptosis and ROS generation. Sirtuin-3 (SIRT3) staining and quantification indicated that dioscin upregulated the expression of neuroprotective SIRT3. Moreover, dioscin induced the formation of autophagosomes and autolysosomes in HT22 cells. Dioscin also enhanced the levels of Beclin-1 and LC3-II while decreased the level of p62. These results suggested that dioscin could activate autophagy in HT22 cells. It was also found that knocking down SIRT3 resulted in the downregulation of Beclin-1, LC3-II and the aggregation of p62, suggesting that SIRT3 was an important regulator in autophagy. Furthermore, we found that knocking down SIRT3 or inhibiting autophagy suppressed the protective effects of dioscin on Aβ1–42 oligomers-induced neurotoxicity, apoptosis and ROS generation. These results revealed that SIRT3 and autophagy functioned together in the neuroprotective mechanisms of dioscin. Therefore, dioscin might be a promising drug to protect against Aβ1–42 oligomers-induced neurotoxicity and reduce neuron damage or death in AD.

阿尔茨海默氏病（AD）是老年人中常见的神经退行性疾病，发病率很高。薯os素是从天然草药中提取的产品，具有多种药理活性。在这项研究中，我们研究了Disocin对淀粉样β肽（Aβ1-42）低聚物处理的HT22细胞的潜在影响。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）分析，Aβ1-42低聚物对HT22细胞具有极大的神经毒性。末端脱氧核糖基转移酶介导的脱氧尿苷三磷酸生物素末端标记（TUNEL）染色和流式细胞术的结果表明，Aβ1-42低聚物导致HT22细胞凋亡增加和活性氧（ROS）的产生。然而，薯os皂素可以显着抑制Aβ1-42寡聚物诱导的神经毒性，并减少细胞凋亡和ROS的产生。Sirtuin-3（SIRT3）染色和定量表明薯di皂素上调了神经保护性SIRT3的表达。此外，薯os皂甙诱导HT22细胞中自噬体和溶酶体的形成。薯os皂素还增加了Beclin-1和LC3-II的水平，同时降低了p62的水平。这些结果表明薯di皂苷可以激活HT22细胞的自噬。还发现敲低SIRT3导致Beclin-1，LC3-II的下调和p62的聚集，这表明SIRT3是自噬的重要调节剂。此外，我们发现敲低SIRT3或抑制自噬抑制了薯os皂素对Aβ1-42低聚物诱导的神经毒性，细胞凋亡和ROS生成的保护作用。这些结果表明SIRT3和自噬在薯os的神经保护机制中共同起作用。因此，薯os皂素可能是预防Aβ1-42寡聚体诱导的神经毒性并减少AD中神经元损伤或死亡的有前途的药物。