State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 1;1220:123663. doi: 10.1016/j.jchromb.2023.123663. Epub 2023 Mar 6.
Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese herbal preparation for the clinical treatment of coronary disease. However, there is a lack of pharmacokinetic studies on YDXNT, and its active ingredients and their mechanism in the treatment of cardiovascular diseases (CVD) are still unclear. In this study, 15 absorbed ingredients in rat plasma after oral administration of YDXNT were quickly identified based on liquid chromatography tandem quadrupole time-of-flight mass spectrometry (LC-QTOF MS), and then a sensitive and accurate quantitative method based on ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-QQQ MS) was established and validated for simultaneous determination of the 15 ingredients of YDXNT in rat plasma, which was then applied to the pharmacokinetic study. Different types of compounds showed various pharmacokinetic characteristics, for instance, ginkgolides with higher maximum plasma concentration (C), flavonoids presenting concentration-time curve with double peaks, phenolic acids with shorter time to reach maximum plasma concentration (T), saponins with long elimination half-life (t) and tanshinones showing fluctuant plasma concentration. Then the measured analytes were regarded as effective compounds and their potential targets and mechanism of action were predicted by constructing and analyzing the compound-target network of YDXNT and CVD. Those potential active compounds of YDXNT interacted with targets such as MAPK1 and MAPK8, and molecular docking showed that the binding free energies of 12 ingredients with MAPK1 were less than -5.0 kcal/mol, indicating that YDXNT intervened in the MAPK signaling pathway to display its therapeutic effect on CVD.
银杏酮酯新纳胶囊（YDXNT）是一种常用于治疗冠心病的中药制剂。然而，目前缺乏关于 YDXNT 的药代动力学研究，其在治疗心血管疾病（CVD）中的活性成分及其作用机制尚不清楚。本研究采用液相色谱-串联四级杆飞行时间质谱（LC-QTOF MS）快速鉴定了大鼠灌胃 YDXNT 后血浆中的 15 种吸收成分，建立并验证了一种超高效液相色谱-三重四极杆串联质谱（UHPLC-QQQ MS）同时测定大鼠血浆中 15 种 YDXNT 成分的灵敏、准确的定量方法，应用于药代动力学研究。不同类型的化合物表现出不同的药代动力学特征，例如，银杏内酯类具有较高的最大血浆浓度（C），黄酮类呈现双峰浓度-时间曲线，酚酸类达到最大血浆浓度（T）的时间较短，皂苷类消除半衰期（t）较长，丹参酮类血浆浓度波动。然后将测定的分析物视为有效化合物，并通过构建和分析 YDXNT 与 CVD 的化合物-靶标网络来预测其潜在的靶标和作用机制。YDXNT 的这些潜在活性化合物与 MAPK1 和 MAPK8 等靶点相互作用，分子对接显示 12 种成分与 MAPK1 的结合自由能均小于-5.0 kcal/mol，表明 YDXNT 干预了 MAPK 信号通路，从而对 CVD 发挥治疗作用。
