The First Affiliated Hospital of Jinan University, Guangzhou 510632, PR China; College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, PR China.
College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
Phytomedicine. 2021 Feb;82:153443. doi: 10.1016/j.phymed.2020.153443. Epub 2020 Dec 23.
Qiliqiangxin Capsule (QLQX), a traditional Chinese medicine (TCM) prescription, is especially used for clinical treatment of chronic heart failure (CHF) in China. However, the holistic quality control of QLQX has not been well established due to lack of system research on the quality marker (Q-marker).
In this study, a new strategy of multi-dimensional "radar chart" mode was proposed to overcome the problem that traditional methods cannot evaluate the multiple properties of Q-markers comprehensively and visually, and the strategy was successfully applied to discover the Q-markers of QLQX.
First, nineteen prototypes that entered the in vivo systemic circulation were selected out as the candidate Q-markers based on our previous studies of chemical and in vivo metabolic profiles. Then, their contents in QLQX were quantitatively analyzed by UHPLC-MS/MS, and the bioactivities on the H9c2 cardiomyocytes cell model was evaluated. The network of in vivo component-target closely related to CHF was further constructed. Finally, a multi-dimensional "radar chart" mode was developed and corresponding Regression Area (RA) and Coefficient Variation (CV) were calculated after data standardization and integration visually based on the Q-marker related multiple characteristics (including the compatibility contribution of herbal medicines, the content, the bioactivity, the in vivo predicted bioavailability and the degree of network pharmacology of candidate components in the TCM prescription).
By comparison of RA and CV of the chemicals in the "radar chart", seven compounds mainly from King and Minister herbs (songorin, calycosin-7-O-β-D-glucopyranoside, astragaloside, tanshinone IIA, ginsenoside Re, hesperidin and alisol A) were screened out as the Q-markers of QLQX, showing the reasonable compatibility contribution and high content in QLQX, preferable pharmacological effect on CHF, as well as good bioavailable characteristics and high target hits in system pharmacology.
The Q-marker discovery of QLQX in this study laid an important foundation for its quality control improvement, and the mode standardized the abstract definitions of Q-marker and realized the comprehensive assessment of multiple properties of Q-marker in TCM prescriptions, which has a reference value for revealing the Q-marker in the quality control researches of TCM prescriptions.
芪苈强心胶囊（QLQX）是一种中药方剂，特别用于中国临床治疗慢性心力衰竭（CHF）。然而，由于缺乏对质量标志物（Q-marker）的系统研究，QLQX 的整体质量控制尚未得到很好的建立。
在本研究中，提出了一种多维“雷达图”模式的新策略，以克服传统方法无法全面、直观地评价 Q-标志物的多种特性的问题，并成功地应用于发现 QLQX 的 Q-标志物。
首先，根据我们之前对化学和体内代谢谱的研究，选择了 19 个进入体内系统循环的原型作为候选 Q-标志物。然后，通过 UHPLC-MS/MS 对 QLQX 中的含量进行定量分析，并评估其对 H9c2 心肌细胞模型的生物活性。进一步构建了与 CHF 密切相关的体内成分-靶网络。最后，根据候选成分在中药方剂中的多种特性（包括草药的配伍贡献、含量、生物活性、体内预测生物利用度和网络药理学程度），通过数据标准化和整合，在视觉上开发了多维“雷达图”模式，并计算了相应的回归面积（RA）和变异系数（CV）。
通过比较“雷达图”中化学物质的 RA 和 CV，从君臣药（松果菊苷、毛蕊异黄酮-7-O-β-D-葡萄糖苷、黄芪甲苷、丹参酮 IIA、人参皂苷 Re、橙皮苷和阿魏酸）中筛选出 7 种主要化合物作为 QLQX 的 Q-标志物，显示出合理的配伍贡献和高含量、对 CHF 的良好药理作用以及良好的生物利用特性和系统药理学中的高靶点命中率。
本研究中 QLQX 的 Q-标志物发现为其质量控制的改进奠定了重要基础，该模式标准化了 Q-标志物的抽象定义，并实现了对中药方剂 Q-标志物多种特性的综合评价，对揭示中药方剂质量控制研究中的 Q-标志物具有参考价值。
