School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; Department of Pharmacy, Chu Hisen-I Memorial Hospital, Tianjin Medical University, Tianjin, 300134, China.
School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; Department of Pharmacy, Tianjin Chest Hospital, Tianjin, 300211, China.
Anal Biochem. 2022 Apr 1;642:114480. doi: 10.1016/j.ab.2021.114480. Epub 2021 Nov 20.
Shen Gui capsule (SGC) has been demonstrated to have a significant treatment effect for coronary heart disease (CHD). Nevertheless, the holistic therapeutic mechanism of SGC in vivo remain poorly interpreted. We aimed to systematically explore the preventive effect and mechanism of SGC on CHD rats using plasma metabolomics strategy. Rat CHD model was established by left anterior descending coronary artery ligation (LAD). Echocardiography, histological analyses of the myocardium and biochemical assays on serum were used to confirm the successful establishment of the CHD model and therapeutic effects of SGC. Then, UHPLC-MS/MS-based plasma metabolomics was combined with multivariate data analysis to screen potential pharmaco biomarkers associated with SGC treatment in the LAD-induced rat CHD model. After SGC treatment, 12 abnormal metabolites considered as potiential pharmaco biomarkers recovered to near normal levels. These biomarkers were involved in several metabolic pathways, including fat and protein metabolism, phenylalanine metabolism, neuroactive ligand-receptor interaction, androgen receptor signaling pathway, and estrone metabolism.These results suggested that SGC achieves therapeutic action on CHD via regulating various aspects of the body such as energy metabolism, neurological disturbances and inflammation, and thus plays a significant role in the treatment of CHD and its complications. The study is useful to systematically understand and analyze the mechanism of SGC's "multipie pathways, multiple levels, multiple targets" prevention and treatment of CHD.
参归胶囊（SGC）已被证明对冠心病（CHD）有显著的治疗作用。然而，SGC 在体内的整体治疗机制仍未得到很好的解释。我们旨在采用血浆代谢组学策略系统地探讨 SGC 对 CHD 大鼠的预防作用及其机制。通过左前降支冠状动脉结扎（LAD）建立大鼠 CHD 模型。通过超声心动图、心肌组织学分析和血清生化测定来确认 CHD 模型的成功建立以及 SGC 的治疗效果。然后，结合多变量数据分析，采用 UHPLC-MS/MS 基于血浆代谢组学筛选与 SGC 治疗 LAD 诱导的大鼠 CHD 模型相关的潜在药效生物标志物。经过 SGC 治疗后，12 种异常代谢物被认为是潜在的药效生物标志物，恢复到接近正常水平。这些生物标志物涉及多种代谢途径，包括脂肪和蛋白质代谢、苯丙氨酸代谢、神经活性配体-受体相互作用、雄激素受体信号通路和雌酮代谢。这些结果表明，SGC 通过调节能量代谢、神经紊乱和炎症等机体的各个方面来发挥对 CHD 的治疗作用，从而在 CHD 及其并发症的治疗中发挥重要作用。该研究有助于系统地理解和分析 SGC 对 CHD 的“多途径、多水平、多靶点”防治作用的机制。
