UPLC-QTOF/MS-based metabolomics analysis of plasma reveals an effect of Xue-Fu-Zhu-Yu capsules on blood-stasis syndrome in CHD rats

Blood-stasis syndrome (BSS) is a specific ZHENG type of coronary heart disease (CHD) in traditional Chinese medicine (TCM). The Xue-Fu-Zhu-Yu (XFZY) decoction is a common herbal formula that has been used for several centuries to treat BSS, but its mechanism has not been thoroughly elucidated to date.In this study, serum lipid, blood haemorheology and metabolomics analyses were performed to depict a complete profile of XFZY capsules for the treatment of CHD with BSS and to reveal the potential mechanism of the XFZY capsules.A rat model of CHD with BSS was generated by combining a high-fat diet (HFD) with a left anterior descending coronary artery (LAD) ligation. After four weeks of treatment with XFZY capsules or simvastatin pills, an echocardiography was performed for a therapeutic evaluation. Blood samples and heart tissues were then collected for further analyses. A UPLC-QTOF/MS-based metabolomics analysis of the plasma was performed, and all metabolic features were fit by PCA and OPLS-DA pattern for the biomarker screen. The identified biomarkers were later implemented into a metabolic pathway analysis. Furthermore, we used qRT-PCR and Western blot analyses to verify the treatment effects of the XFZY capsules.A total of 49 metabolites (VIP>1.0, p < 0.05, RSD%<20%) were identified in the Model rats, and 27 metabolites (VIP>1.0, p < 0.05, RSD%<20%) were identified in the XFZY-H rats. The results of the pathway analysis indicated that the XFZY capsules treated CHD primarily by regulating cardiac energy, phospholipid, polyunsaturated fatty acid (PUFA) and amino acid metabolism. In addition, blood viscosity and serum lipid assays suggested that XFZY capsules could decrease serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and whole blood viscosity at a low shear rate.This study demonstrated that the XFZY capsule effectively decreases serum lipids and whole blood viscosity in CHD with BSS. The underlying metabolic mechanism mainly included improving cardiac energy supply, reducing phospholipid peroxide, maintaining the PUFA metabolic balance and regulating amino acid metabolism.