人参花蕾中新颖结构三萜皂苷的发现及抗肿瘤活性研究

Ginseng Flos was the flower buds of traditional Chinese herb Panax ginseng C. A. Mey. Previously, we screened the antitumor activity using its ethanol extracts in vitro, and found the extracts of ethyl acetate had better inhibitory effect on tumor cells Hep G2and MGC80-3, further studies led to the discovery of six dammarane type triterpenoid saponins with novel C-17 changed side-chain from the extracts, among them, one was a new sapogenin. Then these compounds were tested for cytotoxicity against Hep G2, MGC80-3 and MCF-7 by MTT experiment, and showed good cytotoxicity. Further experiments proved that these compounds could induce the apoptosis of tumor cells. This showed that triterpenoid saponins with novel structure in the ethanol extracts of ginseng flower buds had good antitumor activity. So, we decided to carry out the systemic chemical constituent studies on the active fraction of ginseng flower buds of the C-17 changed side-chain ginsenoside with similar parent nucleus, not significant polarity difference and lower content, identified the chemical structures and clarified the influence on the activity after C-17 side-chain structure was changed, discussed the SAR research of C-17 changed side-chain ginsenoside with the apoptosis of tumor cells, and gained antitumor lead compounds to further pursue the mechanisms of action of antitumor activity. Moreover, this research project will provide basis for the development of novel antitumor agents from ginseng plant.

人参花蕾是我国名贵中药人参含苞待放的花。本课题组通过对其醇提物体外抗肿瘤活性的筛选研究，发现乙酸乙酯萃取物对Hep G2和MGC80-3细胞具较强的抑制作用，并已从该活性组分中分离鉴定了六个结构新颖的C-17侧链结构改变的达玛烷型人参皂苷，其中一个三萜皂苷元为新化合物。MTT实验表明，该类化合物对Hep G2、MGC80-3和MCF-7具有较强的细胞毒作用，进一步研究证明其能诱导肿瘤细胞凋亡。为此，本课题组拟对人参花蕾醇提物活性组分中含有的母核相近、极性差别较小、含量较低的一系列具有C-17不同侧链结构的人参皂苷（元）进行系统的化学成分研究，明确C-17侧链结构改变对活性强弱的影响，探讨C-17侧链结构改变化合物诱导肿瘤细胞凋亡的构效关系，发现具有更佳活性的药物先导物，并从分子和细胞水平上研究其抗肿瘤的作用机制。为人参中新型抗肿瘤药物筛选奠定基础。

人参花蕾是我国名贵中药人参含苞待放的花。本课题组对人参花蕾醇提物体外抗肿瘤活性的筛选研究，发现乙酸乙酯萃取物对Hep G2和MGC80-3细胞具较强的抑制作用。本项目在人参花蕾醇提物抗肿瘤活性导向的指引下，开展了对人参花蕾中的化学成分分离鉴定、单体化合物抗肿瘤活性测定、人参皂苷M1结构修饰和产物活性评价等研究工作。利用HPLC、LC-MS等分离分析技术，共分离鉴定得到皂苷类、黄酮类及脂肪酸酯类共81个单体化合物，其中含12个新皂苷类化合物和1个新黄酮苷类化合物。尤其是得到了一系列分子极性差别较小且含量较低的单体皂苷，并实现了对4对人参皂苷差向异构体的拆分，表征了其S/R型的新化合物的核磁数据。通过单体皂苷对Hep G2、MGC80-3和HL-60的抗肿瘤实验表明，人参皂苷C-20及C-24位S构型的活性强于R构型、羟基酰化能增强活性、糖链较短的皂苷活性较强等初步构效关系。设计了人参皂苷M1的单酯化结构修饰路线，得到了3个抗乳腺癌活性强于M1的3'-单酯化产物。本项目的研究，为掌握人参花蕾的药用物质基础提供了重要的理论参考，建立了微量皂苷的分离纯化及结构鉴定方法，明确了C-17侧链结构改变对人参皂苷抗肿瘤活性的影响，提供了一条改造人参皂苷结构的工艺路线，为人参皂苷的药物开发奠定了一定的基础。