基于谱效先导—整合药理学的滇黄精质量标志物研究

黄精健脾益气、滋阴降火，常用于内热消渴（今糖脂代谢紊乱）等症治疗。云南道地药材滇黄精是药典三个法定品种之一，蕴藏量、产量均有优势，项目组研究了调节糖、脂代谢的活性及新颖机制。然而，其质量评价方法严重滞后于其活性研究与临床应用，仅有其总多糖及总皂苷含量测定，无专属性高的质量评价成分及方法，严重限制该药材应用与开发。项目组提出以滇黄精为研究对象，采用“化学指纹-生物效应”谱效关联分析为先导，筛选其中与调节机体糖、脂代谢功效高度关联的甾体皂苷、黄酮等单体，结合成分的亲缘特异性、结构专属性确定并靶向制备准质量标志物，利用网络药理学、药效学、代谢组学及药物动力学等整合药理学方法对其进行综合评价，确定药动性质良好、对药效贡献度高的滇黄精质量标志物（Q-Marker）。本项目为科学评价滇黄精药材质量奠定基础，阐释其用于糖、脂代谢异常相关疾病治疗的科学依据，对黄精药材的深入开发应用具有重要推动意义。

Polygonati Rhizoma, which could reduce fire, replenishe qi and nourish yin, has been used in the treatment of internal heat and thirst for thousand of years. Polygonatum kingianum Coll. Et Hemsl. is one of the three legal source plants of Polygonati Rhizoma recorded in the Chinese Pharmacopoeia. P. kingianum, as a kind of important "YunYao" has large resource reserves and productions in Yunnan Province. The project team has explored its excellent effects and novel mechanism of regulating glucose and lipid metabolism disorders. However, the limited quality evaluation researches about Polygonati Rhizoma, mainly focused on the determination of total polysaccharides and total saponins, are far behind its great bio-actives and clinic applications. There are no specific quality evaluation substance and no suitable quality evaluation method, which severely limit its application and development. This research aims at find the quality evaluation substances and methods for P. kingianum. The project team proposes that the "chemical fingerprint-biological effect" relationship analysis should be used as the guide to screen and identify the steroid saponins and flavonoids, which are highly correlated with its regulation effect of glucose and lipid metabolism. Phylogenic and structural specificity data will be considered when preparing quasi-quality marker. Then, integrated pharmacology methods, such as network pharmacology, pharmacodynamics, metabolomics and pharmacokinetics will be applied to designate quality marker (Q-Marker) with good pharmacokinetic properties and great contribution to pharmacological efficacy. This project will lay a foundation for scientific evaluation of the quality of P. kingianum and will explain its scientific basis for the treatment of diseases related to abnormal glucose and lipid metabolism. It has important impetus to the wider application of Polygonati Rhizoma.