Zhang Y, Li L, Zhu A, Xiao W, Wang Q
Department of Toxicology, Peking University School of Public Health, Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China.
Key Laboratory of Gastrointestinal Malignant Tumors, Basic Medical College, Fujian Medical University, Ministry of Education, Fuzhou 350108, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2025 Aug 18;57(4):764-771. doi: 10.19723/j.issn.1671-167X.2025.04.022.
To investigate whether escin (ESC) and dextromethorphan (DEX) have the protective effects on the progression and symptoms of Alzheimer disease (AD).
The AD model of () was established by transgenic amyloid β-protein (Aβ protein). Different concentrations of ESC or DEX or 50 μmol/L memantine (MEM) were used to treat the AD model worms, and their lifespan was detected. The movement ability of AD model was evaluated by body bending frequency and head swinging frequency. The changes in cognitive functions of AD model before and after treatment were detected by chemotaxis experiments. The changes in Aβ protein and reactive oxygen species (ROS) content in were detected. The changes in gene pathways related to oxidative stress were detected by Real-time quantitative polymerase chain reaction (RT-qPCR).
At high dose 1 000 μmol/L, ESC or DEX treatment showed no significant effects on the activity of . Compared with untreated worms, the survival time of AD model in the 20 μmol/L ESC and 60 μmol/L DEX intervention groups was significantly extended. In the middle stage of AD progression, the body bending frequency and head swinging frequency of AD model worms after ESC or DEX treatment was significantly increased compared with the untreated control group with DEX being more effective in the recovery of head swinging frequency. For the early cognitive function tests, the chemotaxis index of ESC or DEX treated worms was significantly higher than that of the untreated worms, which correlated with marked reductions in the Aβ protein levels. The reactive oxygen species content in the drug intervention group was also lower than that in the control group. RT-qPCR results showed that ESC could inhibit oxidative stress in the AD model by a 2-fold upregulation of expression.
ESC and DEX could improve the reductions of movement ability and cognitive function in the AD model worms and delay the aggravation of AD-related symptoms. ESC delays the progression of AD possibly by activating the SKN-1/Nrf2 pathway to protect against oxidative injury in the AD model.
研究七叶皂苷（ESC）和右美沙芬（DEX）对阿尔茨海默病（AD）进展及症状是否具有保护作用。
通过转基因淀粉样β蛋白（Aβ蛋白）建立秀丽隐杆线虫的AD模型。使用不同浓度的ESC或DEX或50μmol/L美金刚（MEM）处理AD模型线虫，并检测其寿命。通过身体弯曲频率和头部摆动频率评估AD模型线虫的运动能力。通过趋化性实验检测AD模型线虫治疗前后认知功能的变化。检测线虫中Aβ蛋白和活性氧（ROS）含量的变化。通过实时定量聚合酶链反应（RT-qPCR）检测与氧化应激相关的基因通路的变化。
在高剂量1000μmol/L时，ESC或DEX处理对秀丽隐杆线虫的活性无显著影响。与未处理的线虫相比，20μmol/L ESC和60μmol/L DEX干预组中AD模型线虫的存活时间显著延长。在AD进展的中期，ESC或DEX处理后AD模型线虫的身体弯曲频率和头部摆动频率与未处理的对照组相比显著增加，其中DEX在恢复头部摆动频率方面更有效。对于早期认知功能测试，ESC或DEX处理的线虫的趋化指数显著高于未处理的线虫，这与Aβ蛋白水平的显著降低相关。药物干预组中的活性氧含量也低于对照组。RT-qPCR结果表明，ESC可通过使skn-1表达上调2倍来抑制AD模型线虫中的氧化应激。
ESC和DEX可改善AD模型线虫运动能力和认知功能的降低，并延缓AD相关症状的加重。ESC可能通过激活SKN-1/Nrf2通路来延缓AD的进展，从而保护AD模型免受氧化损伤。
