title: Metabolomics insights into chronic kidney disease and modulatory effect of rhubarb against tubulointerstitial fibrosis.
abstract: Chronic kidney disease (CKD) is a major public health problem worldwide. Rhubarb has been shown to have nephroprotective and anti-fibrotic activities in patients with CKD. However, bioactive fractions and biochemical mechanism of anti-fibrotic properties of rhubarb remain unclear. Here we applied ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry together with univariate and multivariate statistical analyses to investigate the urinary metabolite profile in rats with adenine-induced CKD treated with the petroleum ether (PE)-, ethyl acetate (EA)- and n-butanol (BU)- extracts of rhubarb. Significant differences in renal function, kidney histopathology as well as metabolic profiles were observed between CKD and control rats. Changes in these parameters reflected characteristic phenotypes of CKD rats. We further identified a series of differential urinary metabolites for CKD rats, suggesting metabolic dysfunction in pathway of amino acid, purine, taurine, and choline metabolisms. Treatment with EA, BU and PE extracts of rhubarb improved renal function and histopathological abnormalities including interstitial fibrosis and inflammation, and either fully or partially reversed the abnormalities of the urinary metabolites. Among them, the nephroprotective effect of EA extract was stronger than BU and PE extracts. This work provides important mechanistic insights into the CKD and nephroprotective effects of different rhubarb extract against tubulo-interstitial fibrosis.
authors.affiliation: National Center for Natural Products Research, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, Mississippi, 38677, USA.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: National Institutes for Food and Drug Control, State Food and Drug Administration, No. 2 Tiantan Xili, Beijing, 100050, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.affiliation: Division of Nephrology and Hypertension, School of Medicine, University of California, Irvine, MedSci 1, C352, UCI Campus, Irvine, California, 92697, USA.
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.affiliation: National Institutes for Food and Drug Control, State Food and Drug Administration, No. 2 Tiantan Xili, Beijing, 100050, China.
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Cheng
authors.affiliation: Solution Centre, Waters Technologies (Shanghai) Ltd., No. 1000 Jinhai Road, Shanghai 201203, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11 North Third Ring Road, Beijing 100029, China.
authors.forename: Rui-Chao
authors.initials: RC
authors.lastname: Lin
authors.affiliation: Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, the College of Life Sciences, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.|Division of Nephrology and Hypertension, School of Medicine, University of California, Irvine, MedSci 1, C352, UCI Campus, Irvine, California, 92697, USA.
authors.forename: Ying-Yong
authors.initials: YY
authors.lastname: Zhao
mesh_terms: D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005355:Fibrosis; D007677:Kidney Function Tests; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D009395:Nephritis, Interstitial / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D012372:ROC Curve; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results; D012250:Rheum / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D053773:Transforming Growth Factor beta1