A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

Abstract

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.

Comparative pharmacokinetics of Ding‐Zhi‐Xiao‐Wan preparation and its single herbs in rats by using a putative multiple‐reaction monitoring UPLC‐MS/MS method

“…After accommodation for a week, 24 rats were divided into four groups randomly ( n = 6 in each group). After oral administration of DZXW (25 g/kg), RG (7.5 g/kg), PC (7.5 g/kg), and RP (5 g/kg) to rats, approximately 0.25 mL of blood samples were transferred into heparinised tubes from the suborbital vein with time nodes of 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 36, and 72 h. The dosages of TCM were set on the basis of its clinical applications (four times) 4,19 . The obtained plasma samples were centrifugated at 5000 rpm for 10 min after reaching equilibrium at room temperature for half an hour and then preserved at −20°C.…”

“…The chemical structures of these components are shown in Supporting Information Figure S1. This formula containing four herbs presents a synergistic effect on Alzheimer's disease protection 4–6 …”

Fecal metabolomics based on mass spectrometry to investigate the mechanism of qishen granules against isoproterenol‐induced chronic heart failure in rats

“…The samples were vortexed for 2 min and centrifuged at 14 000 rpm at 4 • C for 10 min to collect the supernatant. In order to assess the system stability and repeatability, a quality control sample was got by mixing equal volumes (50 μL) of every analyzed fecal sample [16]. Before starting injection analysis, the quality control sample was run ten times and injected at intervals of five study samples during the analytical run.…”

Brain metabolomics study for the protective effects of Rhodiola crenulata extract on Alzheimer's disease by HPLC coupled with Fourier transform‐ion cyclotron resonance mass spectrometry

“…Moreover, these singletargeted medicines are associated with various adverse side effects [6]. Benefiting from characteristics of multicomponents, multitargets, and multichannels, traditional Chinese medicines (TCMs) are gradually showing their superiorities over single-targeted medicines in the treatment of AD [7,8].…”