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.
Highlights
Differentiation, extracellular matrix accumulation and tubulo-interstitial fibrosis[3]
The magnitude of increase in urea and CREA concentrations in Chronic kidney disease (CKD)+ Rub, CKD+ petroleum ether extract (PE), CKD+ EA and CKD+ butanol extract (BU) groups was significantly less than those found in the untreated CKD rats
The magnitude of increase in urea and CREA concentrations in CKD+ Rub was more than those found in the CKD+ PE, CKD+ EA and CKD+ BU groups
Summary
Differentiation, extracellular matrix accumulation and tubulo-interstitial fibrosis[3]. Natural medicines or alternative medicines have been used and proven effective in the treatment of different diseases for thousands of years Based on their theoretical therapeutic efficacy and long and wide clinical applications the natural anti-fibrotic medicines have gained increasing attention for prevention and treatment of CKD in Asia, Europe and North America. The biochemical mechanism of action and biological targets of rhubarb and its different components have not been fully elucidated. The UPLC-QTOF/HDMS-based urinary metabolomics was applied to investigate the urinary metabolite profile and potential biomarkers of adenine-induced CKD and the nephro-protective effect of three rhubarb extracts with different polarities including petroleum ether extract (PE), ethyl acetate extract (EA), and n-butanol extract (BU) (polarity: BU > EA > P E) in rats with adenine-induced CKD. The study further sought to identify the bioactive fractions of rhubarb and the mechanisms of their anti-fibrotic actions in this model
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