刺五加多糖抗肿瘤活性的构效关系研究

Polysaccharides are the active components in many medicinal plants. The results from literatures and our previous experiments indicated that the polysaccharides isolated from Acanthopanax senticosus of Araliaceae have good anti-tumor activities. But the contribution to the activity and the structure-activity relationship of the polysaccharide fractions remained unclear. In this project, we are going to fractionate the polysaccharides from Acanthopanax senticosus, analyze the structures and evaluate the anti-tumor activity of each fraction in vitro and in vivo, so that the contribution to the activity of each fractions and the structure-activity relationship could be discussed. After that, the structures of each polysaccharide fraction will be modified by hydrolysis of enzymatic and acidic catalysis to remove some component units, and then, the activity variation caused by the structural modification would be studied. Thus, the effects of the component units such as domains, side chains, methyl esteration and acetylation on the activity would be revealed. Compared with results of structure-activity relationship of ginseng polysaccharides, some rules of structure-activity of polysaccharides in same family but different genus may be sumerized. The innovation of our project is that systematically expolre the relationship of monosaccharide compositions, domain structural features and whole molecular structures of Acanthopanax senticosus polysaccharides and anti-tumor activities. The results in this project will facilitate further research on structure-activity relationship of medicinal plant polysaccharides and reasonable utilization of precious medicinal plant resources.

多糖是许多药用植物的活性成分，我们前期工作表明刺五加多糖具有良好的抑制肿瘤细胞生长的活性，但刺五加多糖中各级分对活性的贡献和构效关系尚不清楚。本项目拟系统分级纯化刺五加多糖，分析各种多糖级分的结构，然后研究每种多糖级分的抗肿瘤活性，探讨刺五加多糖级分的结构与抗肿瘤活性的关系。利用选择性酶解和酸水解等方法修饰多糖结构，研究各种多糖分子的结构变化引起的活性变化，进一步探讨多糖分子中的结构单元对活性的影响，从而揭示多糖的侧链分布和长度、多糖的酯化度等因素对活性的影响。并与人参多糖构效关系的研究结果相比较，尝试总结具有抗肿瘤活性的多糖结构特征。本项目的特色和创新在于系统深入地探索了刺五加多糖的单糖组成、结构域特征以及分子整体结构与抗肿瘤活性的关系。研究结果将促进药用植物多糖构效关系的深入研究以及宝贵药用植物资源的合理利用。

多糖是药用植物的主要活性成分，我们前期工作表明刺五加多糖具有良好的抑制肿瘤细胞生长的活性，但刺五加多糖中各级分对活性的贡献和构效关系尚不清楚。因此，本项目系统深入地探索了刺五加多糖的单糖组成、结构域特征以及分子整体结构与抗肿瘤活性的关系。首先优化了刺五加多糖的提取及分离纯化，通过DEAE-纤维素离子交换层析和Sepharose CL-6B分子筛层析交替组合的方法可将刺五加多糖分级得到中性糖级分ASPN和四种酸性糖级分ASPA-1、ASPA-2、ASPA-1A和ASPA-1B。其次，运用高效液相色谱（HPLC）、红外光谱（FT-IR）和核磁共振波谱（NMR）等方法分析了各级分的结构特征。ASPN为淀粉样葡聚糖，ASPA中有RG-I、AG和XGA结构。ASPA-1中主要含有RG-I和XGA结构域，AG作为支链连接在RG-I,而XGA中的GalA发生甲酯化和乙酰化取代。ASPA-2为RG-I结构的果胶，支链为AG-I结构。ASPA-1A和ASPA-1B均包含RG-I和XGA结构，但ASPA-1B中的GalA甲酯化和乙酰化程度较高。此外，分析比较了不同结构的刺五加多糖的抗肿瘤作用，发现刺五加多糖RG-I结构域是其活性单元。又进一步比较了人参RG-I型果胶（RG-I-4）和刺五加RG-I型果胶（ASPA-2）的抗肿瘤活性，发现五加科药用植物多糖RG-I结构域是其发挥抗肿瘤药效的结构单元，而且RG-I主链上GalA的乙酰化程度可能影响抗肿瘤活性。研究结果将促进药用植物多糖构效关系的深入研究以及宝贵药用植物资源的合理利用。