基于经方黄芩汤的芍药基原考证及品质评价研究

It is necessary to clarify the quality and biological effect equivalence in traditional Chinese medicines (TCMs) derived from multi-species, which is key to refine and improve their current quality standards, and also is the core problem to identify the original species of crude drugs with multi-species in Chinese formulas, and to guarantee their clinical application. In this study, we proposed a new research idea that investigation the differences and correlations between chemical and pharmacological properties in different Huangqin decoction which were respectively made from peony root derived from different species by using modern laboratory methods, the aims are to find the a series of differences in pharmacological activities and chemical composition between red peony root (RPR) and white peony root (WPR), to reveal the pharmacodyamic material basis for their medicinal properties, and then to obtain the Q-markers for quality evaluation of WPR and RPR, which will be serving as useful means for reliable assessment of chemical and biological properties of peony root, and lay the foundation for the safe and scientific application of WPR, RPR and other crude drugs derived from the different species.their medicinal properties, and then to obtain the Q-markers for quality evaluation of WPR and RPR, which will be serving as useful means for reliable assessment of chemical and biological properties of peony root, and lay the foundation for the safe and scientific application of WPR, RPR and other crude drugs derived from the different species.

“多基原”中药的品质和生物效应等同性问题是中药现代进程中普遍关注的难题。仅仅以品种间化学成分的差异难以全面揭示其内在品质的科学内涵。本研究在中医理论指导下，以白芍和赤芍（北赤芍和川赤芍）为研究对象，以经方黄芩汤为载体，采用中药化学、分析化学、中药药理学相结合的研究方法和技术，对多基原芍药放在方剂中同步对比研究，并进行化学/药效关联分析，发现与鉴定引起药效差异的化学成分（群），“基于经方黄芩汤药效与成分关联”阐明白芍和赤芍的药效物质基础，并在此基础上建立白芍和赤芍的质量标准，为黄芩汤中芍药基原确定，白芍和赤芍科学质量标准的修订，也为其他“同属多基原”中药材质量和生物效应等同性共性问题的探索研究提供借鉴。

“一药多基原”中药的质量与生物效应等同性研究是中药标准化所面临的传统难题。本研究以白芍和赤芍（北赤芍和川赤芍）为研究对象，以经方黄芩汤为载体，将不同芍药分别放入方剂中同步对比研究，发现与鉴定引起药效差异的化学成分（群），阐明白芍和赤芍的药效物质基础，为黄芩汤中芍药基原确定和品质评价提供科学依据。. 采用UPLC-Q-TOF-MS/MS技术，建立了不同芍药分别制备的黄芩汤特征指纹图谱，同步比较成分组成差异，借助对照品比对和文献数据，发现与鉴定其共性与差异成分。共47个主要色谱峰被检识，20个来源于黄芩，17个来源于甘草，9个来源于芍药、1个来源于大枣，其中46个色谱峰被鉴定。不同芍药制备的黄芩汤化学成分组成较为相似，主要差异集中于不同品种芍药，主要体现在芍药苷类和鞣质类成分。. 采用UPLC-QqQ-MS/MS结合多成分定量分析手段，建立了不同芍药制备的黄芩汤中17个主要特征成分的同时定量分析方法，定量结果发现氧化芍药苷、儿茶素在黄芩汤（赤芍组）中含量明显高于其他两组；没食子酸、没食子芍药苷在黄芩汤（川赤芍组）中含量最高，芍药苷在黄芩汤（白芍组）中含量相对较少，但芍药内酯苷含量最高。. 采用DSS诱导的小鼠溃疡性结肠炎模型，从动物行为学、病理切片和细胞因子表达水平（IL-1、IL-6）等综合评价和比较不同芍药对经方黄芩汤整体药效的影响。结果表明，与黄芩汤（白芍组）相比，黄芩汤（赤芍）、黄芩汤（川赤芍）组在UC小鼠体重降低率、结肠长度、DAI评分上均有显著差异，但黄芩汤（赤芍）与黄芩汤（川赤芍）间无明显差异。黄芩汤（川赤芍）小鼠的结肠组织病理形态改善最为明显，粘膜缺损情况较赤芍与白芍均有显著改善。结合成分组成及含量比较结果，我们初步认为可能黄芩汤中芍药以川赤芍为最佳，可能与川赤芍中含有大量芍药单萜苷和没食子鞣酸类成分有关，其相关药效评价及机制研究有待于后续进一步研究。