title: A pharmaco-metabonomic study on chronic kidney disease and therapeutic effect of ergone by UPLC-QTOF/HDMS.
abstract: Chronic kidney disease (CKD) is an important public health problem. Ergone has been proved to prevent the progression of CKD. UPLC-QTOF/HDMS was employed for metabolic profiling of adenine-induced CKD and to investigate the nephroprotective effects of ergone. Pharmacology parameters including blood biochemistry, histopathological evaluation and Western blot analysis were performed concurrently. The UPLC-MS data were analyzed by partial least squares-discriminate analysis, correlation analysis, heatmap analysis and mapped to KEGG pathways. Blood and serum biochemistry were observed to be significantly different in the CKD group than in the control group. In conjunction with biochemistry, histopathology and protein expression results, identified metabolites indicated perturbations in fatty acid metabolism, purine metabolism and amino acid metabolism as changes associated with adenine-induced CKD and the interventions of ergone. Upregulated expression of TGF-β1, ED-1, CTGF, bFGF and collagen I was observed in the CKD group. However, downregulated expression of these proteins was observed after oral administration of ergone. These results suggest that expression changes in these proteins had implications for fatty acid metabolism, purine metabolism and amino acid metabolism in the development of CKD and that ergone treatment could delay the development of CKD by normalizing or blocking abnormal changes in biomarker metabolites and protein expression in the CKD group.
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Ying-Yong
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Tian
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, China.
authors.forename: Dan-Qian
authors.initials: DQ
authors.lastname: Chen
authors.affiliation: Solution Centre, Waters Technologies (Shanghai) Ltd., Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
authors.affiliation: National Institutes for Food and Drug Control, State Food and Drug Administration, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002783:Cholestenones; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016002:Discriminant Analysis; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007150:Immunohistochemistry; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics; D015999:Multivariate Analysis; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002783:Cholestenones; D053773:Transforming Growth Factor beta1; C015860:ergosta-4,6,8(14),22-tetraen-3-one; D004875:Ergosterol