DataSheet_1_Non-Targeted Metabolomic Profiling of Coronary Heart Disease Patients With Taohong Siwu Decoction Treatment.pdf

Traditional Chinese medicine is one of the complementary and alternative therapies to improve the prognosis of coronary heart disease (CHD). Taohong Siwu Decoction (THSWD), a classical traditional Chinese medication that promotes blood circulation, is clinically beneficial in CHD. However, the underlying mechanism of THSWD is still unclear. To comprehensively understand the material foundation of the “blood”, it is significantly important to study the differential metabolites involved in the treatment of CHD with Chinese medicinal herb promoting blood circulation in TCM theory. Hence, this study investigated the metabolic profiles of the serum in CHD patients to determine the differential metabolites between the THSWD group and the placebo group. Eleven CHD patients were recruited and divided into two groups randomly and double-blindly. Serum samples were determined by performing non-targeted ultra-performance liquid chromatography with tandem mass spectrometry-based metabolomics. Pearson’s correlation analysis was used to assess the association between identified metabolites and clinical serum indexes of CHD. Based on the result, a total of 513 metabolites were found in the serum of CHD patients, of which 27, involved in 29 metabolic pathways, were significantly different between the two groups. Among the differential metabolites, THSWD upregulated succinylcarnitine in fatty acid metabolism and 5′-methylthioadenosine in cysteine and methionine metabolism compared with the placebo group. However, THSWD downregulated pelargonic acid, involved in FA metabolism; succinate, involved in the tricarboxylic acid cycle; gluconic acid, gluconolactone, and d-glucose, involved in pentose phosphate pathway; glycerophosphocholine, involved in glycerophospholipid metabolism; 8,9-dihydroxyeicosatrienoic acid (8,9-DiHETrE), l-lysine, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, indoxyl sulfate, and 3-ureidopropionate involved in amino acid metabolism compared with the placebo group. Moreover, succinylcarnitine, pelargonic acid, succinate, d-glucose, gluconic acid, l-lysine, N-alpha-acetyl-l-asparagine, 5′-methylthioadenosine, indoxyl sulfate, 8,9-DiHETrE, and 3-ureidopropionate were associated with total cholesterol or low-density lipoprotein. Succinylcarnitine, pelargonic acid, gluconolactone, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, and 5′-methylthioadenosine were associated with activated partial thromboplastin time. Our findings indicated that glycerophosphocholine, 8,9-DiHETrE, 5′-methylthioadenosine, hippurate, indoxyl sulfate, and 3-ureidopropionate might constitute the partial material foundation of the “blood” in CHD patients treated with THSWD.

中医药是改善冠心病（coronary heart disease, CHD）预后的补充与替代疗法之一。桃红四物汤（Taohong Siwu Decoction, THSWD）作为经典的活血化瘀类中药方剂，在冠心病的临床治疗中具有确切获益，但其潜在作用机制仍未阐明。基于中医理论，为全面解析“血”的物质基础，研究活血化瘀类中药干预冠心病时涉及的差异代谢物具有重要学术价值。因此，本研究对冠心病患者的血清代谢谱进行分析，以明确桃红四物汤组与安慰剂组之间的差异代谢物。本研究共招募11名冠心病患者，采用随机双盲法将其分为两组。通过非靶向超高效液相色谱-串联质谱代谢组学技术检测血清样本。采用Pearson相关分析评估已鉴定代谢物与冠心病临床血清指标之间的关联。研究结果显示，冠心病患者血清中共鉴定出513种代谢物，其中27种代谢物涉及29条代谢通路，在两组间存在显著差异。与安慰剂组相比，桃红四物汤可上调脂肪酸代谢通路中的琥珀酰肉碱，以及半胱氨酸与蛋氨酸代谢通路中的5'-甲硫腺苷；同时下调脂肪酸代谢通路中的壬酸、三羧酸循环中的琥珀酸、磷酸戊糖途径中的葡萄糖酸、葡萄糖酸内酯与D-葡萄糖、甘油磷脂代谢通路中的甘油磷酸胆碱，以及氨基酸代谢通路中的8,9-二羟基二十碳三烯酸（8,9-DiHETrE）、L-赖氨酸、N-乙酰-L-天冬氨酸、N-α-乙酰-L-天冬酰胺、马尿酸盐、硫酸吲哚酚与3-脲基丙酸。此外，琥珀酰肉碱、壬酸、琥珀酸、D-葡萄糖、葡萄糖酸、L-赖氨酸、N-α-乙酰-L-天冬酰胺、5'-甲硫腺苷、硫酸吲哚酚、8,9-DiHETrE及3-脲基丙酸与总胆固醇或低密度脂蛋白存在显著关联；琥珀酰肉碱、壬酸、葡萄糖酸内酯、N-乙酰-L-天冬氨酸、N-α-乙酰-L-天冬酰胺、马尿酸盐及5'-甲硫腺苷与活化部分凝血活酶时间存在显著关联。本研究结果表明，甘油磷酸胆碱、8,9-二羟基二十碳三烯酸、5'-甲硫腺苷、马尿酸盐、硫酸吲哚酚及3-脲基丙酸或可构成桃红四物汤治疗冠心病患者时“血”的部分物质基础。