Standardized Xin-Ke-Shu tablets improves the disturbances of lipid, energy, and amino acid metabolism in a rabbit model of atherosclerosis

Abstract

Objective: Xin-Ke-Shu (XKS), a patent drug, used to treat coronary artery diseases in China for many years. Previous research indicates that XKS has similar therapeutic effect as atorvastatin (AS) against atherosclerotic in rabbits. However, biochemical assays demonstrate that XKS could have a different therapeutic mechanism from AS. The aim of this study is to explore the mechanism of XKS therapeutic effect, especially those different from AS. Materials and Methods:1H nuclear magnetic resonance-based metabonomics were applied to profile the low-molecular-weight polar metabolites in the plasma of rabbits fed a high cholesterol diet. Results: Seven of the eleven pathological biomarkers related to atherosclerosis in rabbits were mediated by XKS treatment, namely low-density lipoprotein/very-low-density lipoprotein (LDL/VLDL), lactate, citrate, phosphatidylcholine, glutamine, creatinine, and methionine, as well as two characteristic metabolites of pyruvate and α-glucose. These metabolites involved lipid, energy, and amino acid metabolism, and all could be considered XKS treatment targets. However, AS only affected the metabolic disorders associated with LDL/VLDL and phosphatidylcholine, which is mainly target lipid metabolism. Conclusions: This study indicates that the anti-atherosclerosis effects of AS mainly involve reducing blood–lipid levels, but those of XKS involve a multitargeted activity.

Keywords

• 1H nuclear magnetic resonance
• atherosclerosis
• plasma metabonomics
• polar small molecules metabolites
• Xin-Ke-Shu