title: An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure.
abstract: Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine-induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro-fibrotic proteins including TGF-β1, α-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF.
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: 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: Feng
authors.initials: F
authors.lastname: Wei
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 Ltd., No. 1000 Jinhai Road, Shanghai 201203, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Bai
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: D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology / Q000517:prevention & control; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D055442:Metabolome; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D010949:Plasma / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D010936:Plant Extracts