以活性导向为基础的新疆特有民间药用植物-天山假狼毒中瑞香烷二萜靶向抗胃癌活性物质基础研究

Stelleropsis tianschanica is endemic plants in Xinjiang Uygur Autonomous Region. Although its folk application effect is significant, there was no related research reports. Our research confirmed that daphnane diterpenes were the main material basis of anti-tumor effect of Stelleropsis tianschanica. Further study found that such components may inhibit the survivin protein to anti gastric cancer effect. On the basis of previous work and the combination of advanced methods and technology, we aim to systematically investigate the daphnane constituents of anti gastric activity and mechanism research. Based on the methodology integrated LC–MS dereplication, a variety of chromatography technology and spectroscopic approaches, daphnane diterpenes will be rapidly screened, isolated and elucidated. Virtual screen method was also used to analyze the structure-activity relationships. Meanwhile, in vitro and vivo anti gastric model were established to evaluated the isolated compounds, and its possible mechanism will also be carried out. In this way, our findings will elucidate the anti-cancer efficacy material of daphnane compounds, and provide a theoretical basis for the further development and utilization of Xinjiang endemic plant - Stelleropsis tianschanica.

天山假狼毒为新疆特有植物，民间应用疗效显著，国内外未见其相关研究报道。课题组初步研究证实瑞香烷二萜是天山假狼毒发挥抗肿瘤药效的物质基础，作用机制可能与其抑制Survivin蛋白有关。因此，本项目拟在前期基础上，综合天然药物化学、计算机虚拟筛选、药理学以及分子生物学等多学科先进的技术与方法针对活性部位中丰富的瑞香烷二萜类成分进行研究。包括对瑞香烷二萜类成分快速识别、分离与鉴定，体内外药理模型评价，抗胃癌作用的效应关系分析及可能的作用机制，在深入挖掘天山假狼毒中瑞香烷二萜抗胃癌活性药效物质基础的同时，阐明其作用机制，为新疆特有药用植物-天山假狼毒的进一步开发利用提供理论依据。

瑞香烷型二萜类化合物是一类具有5/7/6三环体系结构的二萜，是主要的生物活性成分，主要分布于瑞香科和大戟科植物中，因其重要的生物活性引起许多研究者的兴趣，现代药理学研究表明此类化合物具有显著的抗肿瘤、抗HIV活性、抗白血病、杀虫等作用，且细胞毒性较小成为近年来最为热门的研究方向。为了寻找更多新的瑞香烷二萜活性化合物，我们对天山假狼毒进行了系统的分离研究，为天山假狼毒的开发利用提供参考，以期为该类化合物的进一步开发利用找到合适的突破口。本实验采用活性跟踪的方法对天山假狼毒二氯部位浸膏进行系统分离，综合运用硅胶、凝胶、ODS反相填料以及半制备高效液相色谱等柱色谱技术从中分离得到56个瑞香烷二萜，包括新化合物12个，发现活性先导化合物1个，且发表SCI论文3篇，中文期刊一篇《天山假狼毒的化学成分研究》。相关研究获新疆维吾尔自治区省部级三等奖一项，中国民族医药协会二等奖一项。项目的开展为新疆特有植物-天山假狼毒中瑞香烷二萜化合物的抗肿瘤药物的进一步开发利用提供理论依据。