Urine metabolomics reveals new insights into hyperlipidemia and the therapeutic effect of rhubarb

Rhubarb has been widely used for the treatment of hyperlipidemia and blood stasis. We conducted an ultra performance liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry-based urinary metabolomic study on the diet-induced hyperlipidemic rats to present new insights into hyperlipidemia and the therapeutic effect of rhubarb. Coupled with blood biochemistry results, a significant difference in metabolic profiles among control, diet-induced hyperlipidemic and rhubarb-treated hyperlipidemic groups by partial least squares-discriminate analysis demonstrated that alterations in global urinary metabolites occurred significantly. Twenty-nine metabolites were identified as potential biomarkers by the accurate mass, isotopic pattern and MSᴱ fragments information in both positive and negative ion modes. Significantly higher levels of octadecanamide, 3-methyluridine, oleamide, ascorbalamic acid, 1-methylnicotinamide, phenylacetylglycine, xanthine, aspartic acid, ribothymidine, 4-aminohippuric acid, methylhippuric acid, arginine and hippuric acid as well as significantly lower levels of 3-O-methyldopa, trimethyltridecanoic acid, S-cysteinosuccinic acid, indole-3-carboxylic acid, creatinine, carnitine, phenylalanine, 2-pyrroloylglycine, phytosphingosine, cyclohexanecarboxylic acid, propionylcarnitine, N-acetylneuraminic acid, cytidine, phenylpropionylglycine, palmitic acid and ribonic acid were observed in the diet-induced hyperlipidemic rats compared with the control rats. However, tendencies of these metabolites were obviously reversed in the rhubarb-treated hyperlipidemic rats. Changes of these metabolites were mainly associated with the perturbations of fatty acid metabolism, amino acid metabolism and nucleoside metabolism. The results indicated the amelioration and the therapeutic effect of rhubarb for hyperlipidemia, and further provided new insights into hyperlipidemia and the therapeutic effect of rhubarb.