UPLC-Q/TOF MS standardized Chinese formula Xin-Ke-Shu for the treatment of atherosclerosis in a rabbit model

Xin-Ke-Shu (XKS), a patent traditional Chinese medicine (TCM) preparation, has been commonly used for the treatment of coronary heart disease in China. In order to understand its mechanism of action, a metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QJTOF MS) was utilized to profile the plasma metabolic fingerprints of atherosclerosis (AS) rabbits with and without XKS treatment. The metabolic profile of model group clearly separated from normal, and that of XKS group was closer to the control group. Metabolites with significant changes during atherosclerosis were characterized as potential biomarkers related to the development of atherosclerosis by using orthogonal partial least-squares-discriminate analysis (OPLS-DA). Twenty potential biomarkers, including L-acetylcarnitine (1), propionylcarnitine (2), unknown (3), phytosphingosine (4), glycoursodeoxycholic acid (5), LPC(14:0) (6), sphinganine (7), LPC(20:5) (8), LPC(16:1) (9), LPC(18:2) (10), LPC(18:3) (11), LPC(22:5) (12), LPC(16:0) (13), LPC(18:1) (14), LPC(22:4) (15), LPC(17:0) (16), LPC(20:2) (17), elaidic carnitine (18), LPC(18:0) (19) and LPC(20:1) (20), were identified by their accurate mass and MSE spectra. The derivations of those biomarkers can be regulated by administration of XKS, which suggested that the intervention effect of XKS against AS may involve in regulating the lipid perturbation including fatty acid beta-oxidation pathway, sphingolipid metabolism, glycerophospholipid metabolism and bile acid biosynthesis. This study indicated that the UPLC-QJTOF MS-based metabonomics not only gave a systematic view of the pathomechanism of AS, but also provided a powerful tool to study the efficacy and mechanism of complex TCM prescriptions. (C) 2014 Elsevier GmbH. All rights reserved.