[关键词]
[摘要]
目的 针对中药复杂的质量属性提出基于质量标志物(quality markers,Q-Marker)的“量效转换”概念,通过多项生物效价的多元整合分析,建立一种药材功效的综合评价方法。方法 以当归为例选取药材中具有抗血小板聚集、Ca2+拮抗舒张血管、抑制NO活性释放以及具有抗炎、抗纤维化作用的抑制核转录因子κB(nuclear factor-κB,NF-κB)和Smad3蛋白(drosophila mothers against decapentaplegic protein-3)的关键药效成分作为Q-Marker,分别建立其含量与对应功效之间的多元量效关系函数。以药材不同生物效价的预测值(yi)与其多批次均值(yi)之间的偏离度(KBio)表示其功效之间的差异。同时引入权重分配系数(Wi)对各生物效价的权重进行优化,并通过质量综合评价指数(Fq)公式(Fq=∑KBio)对上述指标进行整合。结果 利用近红外光谱技术分别检测了500批次当归药材中阿魏酸、绿原酸、洋川芎内酯I、欧当归内酯A和Z-藁本内酯等Q-Marker的含量(xi),通过其含量变化分别预测出其抗血小板聚集与Ca2+、NO、NF-κB和Smad3拮抗活性(yi)。并通过限定Fq值的正态分布的置信区间,筛选出功效相对稳定的药材。结论 确立了一种基于Q-Marker的“量效转换”关系预测当归活血补血的功效的综合评价方法。基于数据分析和近红外光谱快速检测技术,为筛选品质稳定的药材提供了一种新的科学监管模式。
[Key word]
[Abstract]
Objective In light of the complex quality attributes of Chinese materia medica (CMM), the concept of “dose-effect conversion” based on quality markers (Q-Marker) was proposed. A comprehensive evaluation method for the efficacy of CMM was established through multi-component integrated analysis of multiple bio-titers, so as to establish a comprehensive evaluation method for Chinese medicinal materials. Methods Taking Danggui (Angelicae Sinensis Radix, ASR) as an example, the key pharmacodynamic ingredients, with efficacy of improving blood circulation by anti-platelet aggregation, antagonizing Ca2+ for vasodilator, inhibiting NO, anti-inflammatory and anti-fibrosis effect by inhibiting NF-κB, and Smad3 transcription, were selected as Q-Marker. Then the multiple dose-effect relationship between the content (xi) of Q-Marker and corresponding efficacy (yi) were established, respectively. The difference of each bio-titer was indicated by the deviation degree (KBio) between the predicted value of different biological potency (yi) and the mean value of multiple batches (yi). Meanwhile, the weight distribution coefficient (Wi) was introduced to optimize the importance of each bio-titer indexes, and the quality comprehensive evaluation index factor (Fq = ∑KBio) was finally used to integrate the above indexes. Results The contents of Q-Marker including ferulic acid, chlorogenic acid, senkyunolide I, levistilide A, and Z-ligustilide in 500 batches of ASR samples were detected by near infrared reflectance spectroscopy, and the antiplatelet aggregation activity and antagonistic activities of Ca2+, NO, NF-κB, and Smad3 was predicted by the variation of corresponding Q-marker contents, respectively. Coupled with the investigation of the normal distribution interval of the Fq value, the CMM with relatively stable efficacy could be finally screened by the restriction of the confidence interval. Conclusion In this study, a “dose-effect conversion” relationship based on Q-Marker was established to predict different bio-titer of ASR in promoting blood circulation and nourishing blood. And a comprehensive evaluation strategy for the key efficacy of ASR was established by integrating various bio-titer and multiple data analysis, with view to providing a new scientific supervision model for screening CMM with the stable quality.
[中图分类号]
R283.6
[基金项目]
天津市科技援助项目(18YFYZCG00060)