An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure

• Published in: Scientific reports 2016-02, Vol.6 (1), p.22151-22151, Article 22151
• Main Authors: Zhang, Zhi-Hao, Vaziri, Nosratola D., Wei, Feng, Cheng, Xian-Long, Bai, Xu, Zhao, Ying-Yong
• Format: Article
• Language: English
• Subjects: 13; 13/1; 14; 59; 631/45/320; 631/45/608; 64; 82/80; Acetic acid; Adenine; Amino acids; Animals; Biochemistry; Butanol; Carnitine; Collagen; Connective tissue growth factor; Disease Models, Animal; Ethyl acetate; Fibrosis; Fibrosis - pathology; Fibrosis - prevention & control; Histocytochemistry; Humanities and Social Sciences; Immunohistochemistry; Kidney - pathology; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - drug therapy; Kidneys; Male; Metabolism; Metabolites; Metabolome; Metabolomics; multidisciplinary; Nephropathy; Petroleum ether; Plant Extracts - administration & dosage; Plant Extracts - pharmacology; Plasma - chemistry; Public health; Rats, Sprague-Dawley; Renal failure; Renal function; Rheum - chemistry; Rodents; Science; Transforming growth factor-b1; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22151

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.