The discovery of Q-markers of Qiliqiangxin Capsule, a traditional Chinese medicine prescription in the treatment of chronic heart failure, based on a novel strategy of multi-dimensional "radar chart" mode evaluation
The discovery of Q-markers of Qiliqiangxin Capsule, a traditional Chinese medicine prescription in the treatment of chronic heart failure, based on a novel strategy of multi-dimensional "radar chart" mode evaluation
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基于多维度“雷达图”模式评价新策略发现芪苈强心胶囊Q标记物治疗慢性心力衰竭
DOI：
10.1016/j.phymed.2020.153443
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发表时间：
2021-01-08
期刊：
影响因子：
7.9
通讯作者：
Yao, Xinsheng
中科院分区：
文献类型：
--
作者：
He, Liangliang;Liu, Yuehe;Yao, Xinsheng
背景资料：芪苈强心胶囊是我国临床上专门用于治疗慢性心力衰竭的中药方剂。但由于缺乏对质量标志的系统研究，芪灵芪仙的整体质量控制还没有建立起来（Q标记）。目的：针对传统方法不能全面、直观地评价Q标记物的多属性的问题，提出了多维“雷达图”模式的新策略，方法：首先，通过对QLQX的体内化学和代谢特征的研究，筛选出19个进入体内体循环的QLQX原型作为候选的QLQX标记物。采用超高效液相色谱-串联质谱法（UHPLC-MS/MS）对QLQX中各组分的含量进行定量分析，并对H9 c2心肌细胞模型进行生物活性评价。进一步构建了与CHF密切相关的体内组分-靶点网络。最后，基于Q标记相关的多重特征，通过数据标准化和可视化整合，建立了多维“雷达图”模型，并计算了相应的回归面积（RA）和变异系数（CV（包括中药配伍贡献、含量、生物活性、预测的体内生物利用度和中药方剂中候选成分的网络药理学程度）。通过对“雷达图”中化学物质的相对吸收度和相对变异度的比较，筛选出7个主要来源于王母药和臣药的化合物筛选出5个化合物（松果菊苷、毛蕊异黄酮-7-O-β-D-吡喃葡萄糖苷、甘草苷、丹参酮IIA、甘草酸Re、橙皮苷和泽泻醇A）作为QLQX的Q标记物，表明芪连芪仙配伍合理，含量高，对CHF有较好的药理作用，具有良好的生物利用度和较高的系统药理靶点。本研究Q标记的发现为QLQX的质量控制改进奠定了重要基础，该模型规范了Q标志物的抽象定义，实现了对中药方剂Q标志物多属性的综合评价，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。
Background: 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).Purpose: 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.Methods: 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).Results: 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-beta-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.Conclusion: 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.