Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
College of Preclinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Sci Rep. 2017 May 25;7(1):2410. doi: 10.1038/s41598-017-02305-y.
Current chemical markers based quality assessment methods largely fail to reflect intrinsic chemical complexity and multiple mechanisms of action of botanical drugs (BD). The development of novel quality markers is greatly needed. Here we propose bioactive chemical markers (BCM), defined as a group of chemo-markers that exhibit similar pharmacological activities comparable to the whole BD, which can therefore be used to effectively assess the quality of BD. As a proof-of-concept, a BCM-based strategy was developed and applied to Xuesaitong Injection (XST) for assessing the efficacy and consistency of different batches. Firstly, systemic characterization of chemical profile of XST revealed a total number of 97 compounds. Secondly, notoginsenoside R, ginsenoside Rg, Re, Rb and Rd were identified as BCM of XST on treating cardiovascular and cerebrovascular diseases according to Adjusted Efficacy Score following an in vivo validation. Analytical method for quantification of BCM was then developed to ensure the efficacy of XST. Finally, chemical fingerprinting was developed and used to evaluate the batch-to-batch consistency. Our present case study on XST demonstrates that BCM-based strategy offers a rational approach for quality assessment of BD and provides a workflow for chemistry, manufacturing, and controls (CMC) study of BD required by regulatory authority.
目前基于化学标记物的质量评估方法在很大程度上未能反映植物药（BD）的内在化学复杂性和多种作用机制。因此，非常需要开发新的质量标志物。在这里，我们提出了生物活性化学标志物（BCM），将其定义为一组表现出与整个 BD 相似的药理学活性的化学标志物，因此可用于有效评估 BD 的质量。作为概念验证，我们开发并应用了基于 BCM 的策略来评估不同批次的血塞通注射液（XST）的疗效和一致性。首先，对 XST 的化学特征进行了系统的表征，揭示了总共 97 种化合物。其次，根据体内验证后的调整疗效评分，鉴定出三七总皂苷、人参皂苷 Rg、Re、Rb 和 Rd 是治疗心脑血管疾病的 XST 的 BCM。然后，开发了定量 BCM 的分析方法，以确保 XST 的疗效。最后，开发了化学指纹图谱并用于评估批间一致性。我们对 XST 的案例研究表明，基于 BCM 的策略为 BD 的质量评估提供了一种合理的方法，并为监管机构所需的 BD 的化学、制造和控制（CMC）研究提供了工作流程。
