基于蒽醌类成分生物合成途径关键酶基因变异的大黄道地性形成机制研究

Geoherbalism of medicinal materials refers to the medicinal efficacy of Chinese medicine from some special populations (i.e. the source of Chinese medicine) is higher than that from other populations. Higher efficacy of geoherb attributes to the higher content of chemical components or a certain ratio of different components. Geoherbalism also means the chemical differentiation between populations within a source plant species, and forms the different chemical races. The formation of chemical race may be the foundation of the geoherbalism formation of Chinese medicine. Study on the chemical race of medicinal plant can facilitate to clarify the cause of geoherbalism formation of Chinese medicine. The formation of chemical race is the result of the interaction of key enzyme genes in the pathway of the secondary metabolites and environmental factors. Rhubarb is an important bulk medicinal material, and its source plants (Rheum officinale, R. palmatum and R. tanguticum) are ideal candidates for studying geoherbalism formation. Our previous studies indicated that these three 'species' should be merged into one species. Species differentiation is not morphological but chemical, which means rhubarb have formed different chemical races. The chemical race with high content of anthraquinones accords with the geo-authentic producing area of rhubarb. In this project, based on the sampling at population level, the major medicinal components, the key enzyme genes in the biosynthetic pathway of the major medicinal components and environmental factors from the distribution of the source plants of rhubarb will be analyzed. We attempt to explore the causes of the geoherbalism formation of rhubarb. The findings of the present subject would not only explain the mechanism of the geoherbalism formation of rhubarb, but also provide valuable references for studying chemical differentiation and the similar Chinese medicinal materials.

药材的道地性是指中药的基源来自于一些特殊的居群，所含的化学成分含量较高或各种成分比例合理而导致药效较好，也即植物种内发生了化学分化，产生了不同的化学宗。化学宗的形成可能是中药道地性形成的基础，对药用植物化学宗的研究有利于阐明中药道地性形成的原因。化学宗的形成是次生代谢产物代谢途径中关键酶基因和环境因素共同作用的结果。大黄是重要的常用大宗药材，其原植物（药用大黄、掌叶大黄和唐古特大黄）是研究药材道地性形成的理想材料。我们前期的研究结果表明这三个种应被归并为同一个种，种内分化并非形态学上的而是化学上的，即已经形成了化学宗，蒽醌类含量高的化学宗与道地产区相吻合。因此，本项目拟以大黄原植物的居群为研究单元，从其主要药效成分入手，结合主要药效成分代谢途径的关键酶基因和环境因子，综合探讨大黄道地性形成的原因。本项目的完成不仅能够解释中药大黄道地性形成的机制，也为同类型药材及化学分化的研究提供借鉴。

药材的道地性是指中药的基源来自于一些特殊的居群，所含的化学成分含量较高或各种成分比例合理而导致药效较好，也即植物种内发生了化学分化，产生了不同的化学宗。本项目以大黄原植物的居群为研究单元，从其主要药效成分入手，结合主要药效成分代谢途径的关键酶基因和环境因子，综合探讨大黄道地性形成的原因。取得主要研究结果如下：基于大黄的主要药效成分游离蒽醌类含量的结果分析表明不同居群的大黄划分为两大组，芦荟大黄素、大黄素及大黄酸的含量在两组之间具有显著性差异，并与大黄传统的道地产区和非道地产区相吻合。与蒽醌类生物合成途径相关的关键酶分析结果表明，大黄在道地与非道地产区之间存在不同的基因型，基因型与蒽醌类的含量具有显著的相关性。不同分布区的大黄原植物在气候因子方面也存在显著差异，分别对应大黄的非道地与道地产区。总之，无论是药效成分，还是其生物合成途径的关键酶基因和环境因子均可将大黄原植物划分为两大组，且分组趋势一致并与传统的大黄道地与非道地产区吻合，大黄道地性的形成是基因与环境共同作用的结果。本项目的完成解释了中药大黄道地性形成的机制，也为同类型药材及化学分化的研究提供借鉴。