Abstract

Salvia miltiorrhiza (SM) coupled with Dalbergia odorifera (DO) has been used to relieve cardiovascular diseases in China for many years. Our previous studies have integrated that SM—the volatile oil of DO (SM-DOO)—has a cardioprotective effect on chronic myocardial ischemia based on a pharmacological method, but the cardioprotective mechanism has not been elucidated completely in the metabonomic method. In the present study, a metabonomic method based on high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was performed to evaluate the effects of SM-DOO on chronic myocardial ischemia induced by an ameroid constrictor, which was placed on the left anterior descending coronary artery (LAD) of pigs. Pigs were divided into three groups: sham, model, and SM-DOO group. With multivariate analysis, a clear cluster among the different groups was obtained and the potential biomarkers were recognized. These biomarkers were mainly related to energy metabolism, glucose metabolism, and fatty acid metabolism. Furthermore, the protein expressions of phosphorylated AMP-activated protein kinase (p-AMPK) and glucose transporter-4 (GLUT4) were significantly upregulated by SM-DOO. The result indicated that SM-DOO could regulate the above biomarkers and metabolic pathways, especially energy metabolism and glucose metabolism. By analyzing and verifying the biomarkers and metabolic pathways, further understanding of the cardioprotective effect of SM-DOO with its mechanism was evaluated. Metabonomic is a reliable system biology approach for understanding the cardioprotective effects of SM-DOO on chronic myocardial ischemia and elucidating the mechanism underlying this protective effect.

Highlights

  • Coronary artery disease is the largest composition of cardiovascular diseases, which is the leading cause of morbidity and mortality [1, 2]

  • The results suggest that pretreatment of SMDOO can restore the pathological process of chronic x102 1

  • The metabolic profiling of the pigs’ plasma in chronic myocardial ischemia and the effect of Salvia miltiorrhiza (SM)-Dalbergia odorifera (DOO) were revealed using HPLC-Q-TOF-mass spectrometry (MS) followed by multivariate analysis

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Summary

Introduction

Coronary artery disease is the largest composition of cardiovascular diseases, which is the leading cause of morbidity and mortality [1, 2]. Previous investigations suggested beneficial effects of traditional Chinese medicine in the treatment of coronary artery disease, including Salvia miltiorrhiza (SM), Panax notoginseng, Ligusticum chuanxiong, and Dalbergia odorifera (DO) [4,5,6]. We reported that SM—the volatile oil of DO (SM-DOO)—exhibited a significant effect in myocardial ischemia/reperfusion (MI/R) injury rats in both traditional pharmacological methods and metabonomic methods [13, 14]. On this basis of these data, traditional pharmacological methods (myocardial injury markers, myocardial oxygen consumption, ventricular function, and myocardial tissue damage) were used to evaluate the therapeutic effect of SM-DOO on chronic myocardial ischemia in pigs [15]. A more systematic approach to elucidating its possible mechanisms is lacking

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