基于药用植物亲缘学的蒙药达格沙的“有效性-物质基础-质量标记物”研究

Medicinal plants in the Genus Oxytropis are widely distributed in Inner Mongolia, and some species are known to possess drug value. It is known as "Ta-gesha" used in Mongolian medicine,which consists mainly of the dried herb of Oxytropis myriophylla (Pall) DC.,and O.hirta Bge. There are many kinds of folk are often used as a substitute for"Ta-gesha"..The project is planned to study covering historic,botanical,and clinical aspects of "Ta-gesha"under the theoretical guidance of pharmacophylogenetic study. We plan to study their efficacy and effective material basic of the herb of Oxytropis myriophylla and O.hirta which are used frequently in Mongolian medicine as"Ta-gesha" authentic medicinal materials. We expect to find bioactive natural compounds,determine their chemical structures, and examine the pharmacological activity of the components and extracts to provide a rational approach for their traditional use. Then, on this basis,we clarify Q-marker and establish a comprehensive system for quality control and ensure the quality that is stable and controllable.In addition,medicinal plants whin the Genus Oxytropis in various regions will be widely collected especially the substitute of "Ta-gesha", to research in molecular biology genome related information, explore its phylogenetic relationship based on Q-marker and the main secondary metabolites of the genus.We expect to clarify the correlation between phylogeny，chemical constituents and the traditional efficacy (pharmacological activity) of Oxytropis plants，and then to evaluate the drug efficacy of medicinal plants in the Genus Oxytropis..Through publication of this research based on traditional pharmacology,plant chemistry, analytical chemistry, molecular pharmacognosy, resource chemistry and pharmacology information we will provide a scientific basis for the rational and sustainable utilization of medicinal plants in the Genus Oxytropis.

棘豆属药用植物种类较多，广泛分布于内蒙古地区，民间疗效确切。其中，多叶棘豆和硬毛棘豆是蒙医习用的特色药材，蒙药名“达格沙”，另外，本属许多种类在民间和临床也用作“达格沙”的代用品，与其有相似的疗效。因此，本项目拟在药用植物亲缘学理论指导下，对“达格沙”类蒙药传统药物学、原植物生物多样性及临床使用情况进行调查，以正本清源；对蒙药“达格沙”正品药材多叶棘豆和硬毛棘豆的有效性和物质基础进行研究，确定质量标记物，建立能全面系统地反映其内在质量的客观评价体系和指标；广泛收集棘豆属药用植物特别是“达格沙”的代用品，采用分子生物学手段研究基因组亲缘关系信息；以质量标记物和主要次生代谢产物为主，探讨该属植物的化学亲缘关系；同时阐明棘豆属药用植物亲缘关系-化学成分-传统疗效（药理活性）之间的相关性及内在规律，进而对棘豆属药用植物的用药有效性进行评价，为扩大该属资源的开发利用方面奠定理论依据。

棘豆属Oxytropis药用植物种类较多，广泛分布于内蒙古地区。多叶棘豆和硬毛棘豆是蒙医习用的特色药材，蒙药名“达格沙”，另外，本属许多种类在民间用作“达格沙”的代用品，与其有相似的传统疗效。本项目在药用植物亲缘学理论指导下，采用传统药物学、植物及分析化学、生药学、资源化学、代谢组学和药理学等多学科方法对棘豆属药用植物进行了深入系统的研究和整理。1）进行了棘豆属文献资料的整理和民间疗效调查，完成了棘豆属药用植物的传统药物学研究。2）完成蒙药“达格沙”多叶棘豆和硬毛棘豆，以及砂珍棘豆、刺叶柄棘豆的植物化学研究，阐明药材的质量标记物主要为黄酮类。 3）建立了多叶棘豆、硬毛棘豆、砂珍棘豆以及刺叶柄棘豆的指纹图谱及指标性成分的含量测定方法；建立了总黄酮含量测定方法；测定了水分、总灰分以及酸不溶性灰分，和生药学研究一起，构建了药材科学的质量评价体系。4）建立了多叶棘豆和硬毛棘豆的指纹图谱及对照图谱。从化学成分的角度上看两者差异很大，不能代替使用。所建立的指纹图谱具有稳定性和可控性，能够区分蒙药“达格沙”正品及代用品。5）结合传统功效，对12种棘豆属药用植物及其中的5个黄酮单体，进行了抗炎、抗癌活性研究。6）完成了多叶棘豆、硬毛棘豆、砂珍棘豆、二色棘豆、刺叶柄棘豆、蓝花棘豆、瘤果棘豆、薄叶棘豆、阴山棘豆、线叶棘豆、大花棘豆以及缘毛棘豆的生药学研究，建立了从显微水平准确鉴别棘豆属药用植物的方法。7）使用单分子实时测序（SMRT），获得多叶棘豆、硬毛棘豆、砂珍棘豆、二色棘豆的转录组信息，为分析种间基因差异表达提供了有价值的基础。8）采用基于UPLC-QTOF-MS的植物代谢组学技术，鉴定了多叶棘豆、硬毛棘豆、砂珍棘豆、二色棘豆4种不同棘豆中的化学成分并挖掘潜在的代谢差异物。 .本项目的实施对提高棘豆属药用植物的认知度，特别是为“达格沙”类蒙药的开发和可持续利用提供比较充分的理论依据和基础。