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

Yuhang Zhao; Shanshan Nie; Min Yi; Ning Wu; Wenbo Wang; Zheyu Zhang; Ye Yao; Dongsheng Wang

doi:10.1016/j.jep.2019.111908

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

J Ethnopharmacol. 2019 Sep 15:241:111908. doi: 10.1016/j.jep.2019.111908. Epub 2019 Apr 25.

Authors

Yuhang Zhao¹, Shanshan Nie², Min Yi³, Ning Wu⁴, Wenbo Wang⁵, Zheyu Zhang⁶, Ye Yao⁷, Dongsheng Wang⁸

Affiliations

¹ Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: zyh084@csu.edu.cn.
² Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: nss085@csu.edu.cn.
³ Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: yimin66@csu.edu.cn.
⁴ Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: 373840809@qq.com.
⁵ Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: wangwenbo@csu.edu.cn.
⁶ Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. Electronic address: zhangzy3904@csu.edu.cn.
⁷ Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: yaoye123456@aliyun.com.
⁸ Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Traditional Chinese Medicine for Gan of State Administration, Central South University, Changsha, Hunan, 410008, China. Electronic address: wdsh666@126.com.

PMID: 31029757
DOI: 10.1016/j.jep.2019.111908

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Blood-stasis syndrome; Cardiovascular; Metabolomics; Myocardial infarction; Traditional Chinese medicine; Xue-Fu-Zhu-Yu.

MeSH terms

Animals
Chromatography, High Pressure Liquid / methods
Coronary Disease / blood*
Coronary Disease / pathology
Drugs, Chinese Herbal / pharmacology*
Hemostasis / drug effects
Lipids / blood
Male
Mass Spectrometry / methods
Metabolic Networks and Pathways / drug effects
Metabolomics
Myocardium / pathology
Rats, Sprague-Dawley
Syndrome

Substances

Drugs, Chinese Herbal
Lipids
Xue-Fu-Zhu-Yu decoction