Wang Dan, Shi Chang, Ge Zhen-Hua, Wei Yu-Xi, Liu Tian-Tian, Wang Yue, Zhou Xin-Feng, Yang Zi-Jun, Wang Wei-Ting, Zhang Yan-Wen, Zhu Xue-Hui, Zhang Jun, Li Ying, Gong Min, Wu Xiao-Hui, Duan Hong-Quan
College of Pharmacy, Tianjin Medical University, Tianjin, China.
Department of Pharmacy, Tianjin Huanhu Hospital, Tianjin, China.
Front Pharmacol. 2021 Mar 25;12:650438. doi: 10.3389/fphar.2021.650438. eCollection 2021.
: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. : A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. : GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. : GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.
冠心舒通胶囊（GXSTC）是一种中药，在中国已用于治疗冠心病（CHD）多年。然而，GXSTC抗冠心病的整体机制仍不清楚。因此，本文的目的是采用代谢组学策略系统地探索GXSTC治疗冠心病大鼠的作用机制。
通过结扎左冠状动脉前降支（LAD）诱导建立冠心病模型。对每组进行超声心动图检查；测定血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）和天冬氨酸转氨酶（AST）的含量；并测量心肌梗死面积。采用基于超高效液相色谱-串联质谱（UHPLC-MS/MS）的非靶向代谢组学方法分析血浆中的代谢物。然后，进行多元统计分析，以筛选与LAD诱导的大鼠冠心病模型中GXSTC治疗相关的潜在生物标志物。最后，使用MetaboAnalyst 4.0平台进行代谢途径富集分析。
GXSTC能够调节CK、LDH和AST的含量；恢复受损的心功能；并显著缩小模型大鼠的心肌梗死面积。通过基于UHPLC-MS/MS的非靶向代谢组学分析，鉴定出GXSTC治疗冠心病的22种生物标志物和9条代谢途径。
GXSTC调节LAD诱导的冠心病大鼠内源性成分的代谢紊乱。GXSTC抗冠心病的机制主要与氨基酸、脂质和激素代谢的调节有关。本研究提供了GXSTC抗冠心病作用机制的整体视图。
