School of Pharmacy and Food Science, Zhuhai College of Jilin University, Zhuhai, P. R. China.
National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, P. R. China.
J Sep Sci. 2020 Apr;43(8):1458-1465. doi: 10.1002/jssc.201900944. Epub 2020 Feb 26.
As a well-known traditional Chinese medicine formula, Ding-Zhi-Xiao-Wan has long been used for the routine treatment of Alzheimer's disease. However, the mechanism of Ding-Zhi-Xiao-Wan in treating Alzheimer's disease is unclear. Therefore, a nontargeted metabolomics method based on ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry has been established to explore the metabolic variations in the urine of Alzheimer's disease rats and investigate the therapeutic mechanism of Ding-Zhi-Xiao-Wan on Alzheimer's disease. To develop a better rat model of Alzheimer's disease, amyloid β25-35 was injected into the bilateral hippocampus of Sprague-Dawley rats. Multivariate analysis approaches were applied to differentiate the urine components between the four groups. Thereafter, a targeted metabolomics method was used to verify the identified endogenous metabolites and determine the mechanism of action of Ding-Zhi-Xiao-Wan. Altogether, 26 potential biomarkers were found, of which 15 biomarkers (10 of which are potential biomarkers found in nontargeted metabolomics) were identified. The results show that Ding-Zhi-Xiao-Wan mainly affects the pathways of taurine and hypotaurine metabolism, tryptophan metabolism, and phenylalanine metabolism. Ding-Zhi-Xiao-Wan might play a role in the treatment of Alzheimer's disease by mediating antioxidative stress, regulation of energy metabolism, improvement of intestinal microbes, and protection of nerve cells.
作为一种著名的中药方剂，定志小丸长期以来一直被用于常规治疗阿尔茨海默病。然而，定志小丸治疗阿尔茨海默病的机制尚不清楚。因此，建立了一种基于超高效液相色谱-四极杆飞行时间质谱的非靶向代谢组学方法，以探索阿尔茨海默病大鼠尿液中的代谢变化，并研究定志小丸治疗阿尔茨海默病的作用机制。为了开发更好的阿尔茨海默病大鼠模型，将淀粉样蛋白β25-35 注入 Sprague-Dawley 大鼠双侧海马。应用多元分析方法来区分四组大鼠尿液成分。然后，采用靶向代谢组学方法来验证鉴定的内源性代谢物，并确定定志小丸的作用机制。共发现 26 个潜在的生物标志物，其中 15 个（其中 10 个是在非靶向代谢组学中发现的潜在生物标志物）被鉴定。结果表明，定志小丸主要影响牛磺酸和次牛磺酸代谢、色氨酸代谢和苯丙氨酸代谢途径。定志小丸可能通过介导抗氧化应激、调节能量代谢、改善肠道微生物和保护神经细胞来发挥治疗阿尔茨海默病的作用。
