Evaluation of the anti-atherosclerosis effect of Shanhuaxiaozhi Formulation by combination of GC–MS-based metabolomics and TMT-based proteomics technology

Abstract Objective Shanhuaxiaozhi formulation (SHXZF) is a traditional Chinese medicine preparation composed of Saffron, Crataegi Fructus, Chrysanthemi Flos, Tangerine Peel and Fructus Lycii. It is used in clinics for treating atherosclerosis with promising evidence of efficacy. Although some of the drugs in SHXZF have been reported to have significant therapeutic effects on atherosclerosis, the metabolic regulation and underlying mechanism of SHXZF during the remission of atherosclerosis are still unclear. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of SHXZF in treating atherosclerosis. Methods Serum samples and aortic arch tissue from male ApoE−/− mice and C57BL/6L mice were analyzed respectively using gas chromatography–mass spectrometry (GC–MS) based metabolomics technology and Tandem Mass Tags (TMT) based quantitative proteomics technology. Metabonomics and proteomics data were integrated to analyze the mechanism of SHXZF in the treatment of atherosclerosis. Results A total of 24 potential biomarkers and 70 differential proteins were identified. These substances were mainly involved in three biological pathways: the cAMP signaling pathway, the lipid metabolism pathway, and the myocardial contraction pathway. Conclusions The results suggested that SHXZF could effectively treat atherosclerosis, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of SHXZF on atherosclerosis.