基于"活性"指纹图谱的不同品种来源陈皮应用价值的分析与评价

Citri Reticulatae Pericarpium (CRP, Chenpi in Chinese), the dried ripe pericarp of Citrus reticulata Blanco or its cultivars, is one of the most popular traditional medicinal herbs with great medicinal values. China is abundant in citrus resources of various cultivars. However, the quality of various citrus peel from different cultivars are significantly uneven. The confused application on these medical herbs might have a negative influence on the pharmacological effect of CRP. Although HPLC fingerprint is widely used as a traditional mean of quality control for herbs, there are so many defects such as chemical compositions remained unknown and irrelevant to pharmacological effects. Therefore, the establishment of a more scientific quality assessment on medicinal value for CRP should be quite important. So that, the purpose of this project is to establish a quality evaluation system for various CRP based on the "activity fingerprint". Firstly, in order to explore the pharmacodynamic material of CRP, some systematic separation and analysis methods coupled with high-speed countercurrent chromatography (HSCCC), LC-MS, LC-PDA would be carried out, which based on the pharmacological model of relieving cough and resolving phlegm, antitumor cell model in vitro and Caco-2 cell model. Then, On the basis of the full manifestation of the pharmacodynamic material in CRP, analysis and evaluation would be carried out and focused on construction method and elucidation process of “activity fingerprint”, and the results may be in favor of revealing the genuineness feature of various CRP in material basis aspect through comparison of the types and the contents of effective constituents and the differences in similarity of chemical constituents. The results of the project would not only play an important role on the quality evaluation and on the guidance of identity for various CRP, but also contribute to the protection of the improved cultivars of CRP and the effective development and utilization of citrus resources.

陈皮（橘皮）为芸香科植物橘及其栽培变种的干燥成熟果皮。我国是柑橘生产大国，柑橘品种繁多，不同品种来源的陈皮之间混用情况严重，已极大地影响到了陈皮的实际应用效果。因此，建立适当的方法并克服常规质量评价方法存在片面性、模糊性等问题，科学地评价各种陈皮的应用价值就显得尤为重要。本项目拟在建立能体现陈皮传统止咳化痰功效的小鼠动物模型、现代体外抗肿瘤细胞模型及Caco-2 细胞模型模拟机体吸收的基础上，结合HSCCC、LC-MS、LC-PDA等多种分离分析手段探明陈皮有效部位的效应物质，进一步在效应物质基础上构建与药理活性及化学成分相关联的陈皮“活性”指纹图谱，并对其进行充分解析，以求在效应成分的“数”与“量”及成分整体相似性的差异上对不同品种来源的陈皮质量进行全面、深入地评价。课题的实施，不仅可以为各种陈皮的鉴定和合理应用提供科学的依据，而且能为陈皮品种的保护及资源的有效开发利用提供一定的借鉴。

陈皮（橘皮）为芸香科植物橘及其栽培变种的干燥成熟果皮。我国是柑橘生产大国，柑橘品种繁多，不同品种来源的陈皮之间混用情况严重，已极大地影响到了陈皮的实际应用效果。因此，建立适当的方法并克服常规质量评价方法存在片面性、模糊性等问题，科学地评价各种陈皮的应用价值就显得尤为重要。.主要研究内容：（1）制备了陈皮黄酮类有效部位，并对其化学成分进行了分离鉴定；（2）结合传统功效模型及现代药理模型，对陈皮黄酮类有效部位及其单体成分进行了活性评价，明确了效应成分；（3）构建了陈皮“活性”指纹图谱，结合指纹图谱对不同品种来源陈皮的质量进行了分析与评价；（4）对2015年版《中国药典》陈皮标准提出了修订建议。.重要结果及关键数据：（1）制备了陈皮黄酮类有效部位，从其中鉴定出了41个化学成分，包括7个黄酮氧苷、4个黄酮碳苷和19个多甲氧基黄酮；（2）通过止咳化痰功效实验和抗肿瘤、降糖活性分析，明确了陈皮效应成分，包括橙皮苷及多甲氧基黄酮类成分如川陈皮素、橘皮素、3,5,6,7,8,3’,4’-七甲氧基黄酮和5-羟基-6,7,8,3’,4’-五甲氧基黄酮等；（3）建立了22个品种来源合计92批不同产地的陈皮药材的“活性”指纹图谱，鉴定了指纹图谱中17个共有峰结构，结合5种主要黄酮类效应成分的含量测定结果及相似度评价研究结果，表明除药典规定的陈皮三种主要品种茶枝柑（广陈皮）、福橘（建陈皮）和大红袍（川陈皮）外，砂糖橘等9个品种作为陈皮的应用价值较高，而温州蜜柑等7个品种作为陈皮的应用价值较低。.课题的实施，不仅可以为各种陈皮的鉴定和合理应用提供科学的依据，而且能为陈皮品种的保护及资源的有效开发利用提供一定的借鉴。