美洲和东北刺人参中抗肿瘤活性功能成分及作用机制研究

Oplopanax horridus and Oplopanax elatus classified as the genus Oplopanax have anticancer activities, however, the anticancer components and the mechanism are unclear. Previous studies indicated that the abundant polyynes showed strong anti-proliferative effects on several cancer cell lines, this project intends to uncover more anticancer polyynes and clarify their effective mechanism from O.horridus and O.elatus. However, the polyynes also had strong cytotoxic effects on LO2 cells from the normal human liver tissue. As tonics, O.horridus and O.elatus have not showed any significant liver toxicity in the long historical clinical applications. Studies have indicated that the hydrophilic component from the root extract of O.horridus showed no cytotoxic effects, which could promote proliferation of LO2 cells. The results suggest that the anticancer effects of O.horridus are the interaction between polyynes and the hydrophilic component. Therefore, it will provide theoretical guidance and solid evidence to facilitate the clinical application of O.horridus and O.elatus to clarify the key effective, up-effective and detoxicant, toxic, detoxicant and inactive ingredients by evaluating pharmacodynamic action of the composite with polyyne and hydrophilic ingredients together. The resource of O.horridus is rich while O.elatus is an endangered species, investigation on the anticancer effects and mechanism of the two herbs is conducive to their protection, research and development. By discovering effective and low toxic anticancer leading compounds and their composite from natural resources, the project will contribute for our national new drug development.

刺人参属美洲和东北刺人参有抗肿瘤活性，而刺人参抗癌活性的物质基础及机制尚不明确。刺人参高含量炔醇化合物对肿瘤细胞有较强的细胞毒作用，本项目将从刺人参中筛选更多抗癌活性炔醇类成分及明确其作用机制。研究发现刺人参炔醇对人正常组织肝细胞LO2也有较强的细胞毒性，而刺人参有补益功效，长期临床使用并未表现明显的肝脏毒性。美洲刺人参根提物亲水组分无细胞毒性且可促进LO2细胞的增值，揭示美洲刺人参的抗肿瘤活性是炔醇与亲水成分相互作用的综合结果。因此，采用炔醇与亲水组分组合用于抗肿瘤活性筛选药效关键成分、增效减毒成分、毒性成分、减毒成分及无效成分将为刺人参临床使用提供理论指导和科学依据。美洲刺人参资源丰富，但东北刺人参处于濒危状态，进行两种刺人参抗肿瘤物质基础研究，有利于刺人参保护和开发利用。本项目对于从天然产物中发现高效低毒的抗癌活性先导化合物及其组合物有重要意义，为促进我国创新药物的发展做出有益探索。

刺人参属美洲和东北刺人参有抗肿瘤活性，而刺人参抗癌活性的物质基础及机制尚不明确。刺人参高含量炔醇化合物对肿瘤细胞有较强的细胞毒作用，本项目从刺人参中筛选更多抗癌活性炔醇类成分及明确其作用机制。前期研究揭示美洲刺人参的抗肿瘤活性是炔醇与亲水成分相互作用的综合结果。因此，采用炔醇与亲水组分组合用于抗肿瘤活性筛选药效关键成分、增效减毒成分、毒性成分、减毒成分及无效成分将为刺人参临床使用提供理论指导和科学依据。课题主要研究内容包括：<1> 美洲和东北刺人参炔醇和亲水成分的分离与结构鉴定; <2> 美洲和东北刺人参炔醇化合物的细胞毒活性及构效关系研究; <3> 美洲和东北刺人参炔醇化合物抗肿瘤活性机制研究; <4> 亲脂性活性炔醇与亲水性组分组合药效研究; <5> 利用动物模型评估炔醇类成分在抗肿瘤作用中的效应。从美洲刺人参中分离鉴定49个化合物，其中16个为新化合物；东北刺人参中分离鉴定22个化合物，其中3个新化合物。细胞增殖和肿瘤动物实验显示刺人参中炔醇类成分具有很好抗肿瘤活性，而酚苷类成分无相关活性，但其对炔醇具有减毒增效作用；主要作用机制与肿瘤细胞周期阻滞及诱导细胞凋亡有关。本项目对于从天然产物中发现高效低毒的抗癌活性先导化合物及其组合物有重要意义，为促进我国创新药物的发展做出有益探索。