Urinary metabonomic evaluation of the therapeutic effect of traditional Chinese medicine Xin-Ke-Shu against atherosclerosis rabbits using UPLC–Q/TOF MS

• We study the protection of XKS on AS rabbit using a metabonomic approach.
• 15 urinary biomarkers were used to evaluate the mechanism of XKS.
• Ten metabolic pathways were to illustrate the pharmacological action of XKS.

Intervention of a traditional Chinese medicine (TCM) Xin-Ke-Shu (XKS) against urinary metabolic disturbance of atherosclerosis (AS) rabbits was investigated based on a metabonomic approach using an ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC–Q/TOF MS). Fifteen metabolites were characterized as novel potential biomarkers to delineate the pharmacological effect of XKS with principal component analysis (PCA), orthogonal partial least-squares-discriminant analysis (OPLS-DA) and shared and unique structure plot (SUS-plot), which were involved into citrate cycle, lysine metabolism, glutathione metabolism, proteolysis, glycerophospholipid metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism, arachidonic acid metabolism and fatty acid β-oxidation pathway. With these altered metabolic pathways as possible drug targets, XKS treatment could provide satisfactory effect on the regulations of these perturbations. Our results showed that the developed metabonomic approach offered a systematic view of AS-related metabolome and provided a new methodological cue for dissecting the underlying mechanism of TCM in treating AS.