土家族药物扣子七中三萜皂苷成分及抗肿瘤活性研究  

Study on antitumor activity of triterpenoid saponins from Tujia ethnomedicine Kouziqi

作　　者：王晓娟 谢谦 刘杨 陆世银 Muhammad Daniyal 李斌 段淑莉 龚力民 梁娜 毛羽 于勇 王炜 WANG Xiao-juan;XIE Qian;LIU Yang;LU Shi-yin;Muhammad Daniyal;LI Bin;DUAN Shu-li;GONG Li-min;LIANG Na;MAO Yu;YU Yong;WANG Wei(Hunan Food and Drug Vocational College,Changsha,410208,China;TCM and Ethnomedicine Innovation&Development International Laboratory,Innovative Drug Research Institute,Sino-pakisitan TCM&Ethnomedicine Research International Cooperation Base(Hunan Province),School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;Department of Phamacy,Liuzhou Traditional Chinese Medical Hospital Guangxi Zhuang Autonomous Region,Liuzhou 545026,China)

机构地区：[1]湖南食品药品职业学院,湖南长沙410208 [2]湖南中医药大学药学院,创新药物研究所,中药民族药物创新发展实验室,中国-巴基斯坦中医药民族医药研究国际合作基地(湖南),湖南长沙410208 [3]广西壮族自治区柳州市中医医院药学部,广西柳州545026

出　　处：《中草药》2020年第7期1831-1838,共8页Chinese Traditional and Herbal Drugs

基　　金：湖南省自然科学基金科教联合项目(2017JJ5041);国家自然科学基金青年基金资助项目(81703819);湖南省大学生研究性学习和创新性实验计划项目(2018-413)。

摘　　要：目的研究土家族药物扣子七Panax japonicus var. major中三萜皂苷类成分,对其抑制肿瘤细胞增殖活性进行筛选,并初步探讨化合物结构与活性的关系。方法应用多种色谱方法对土家族药物扣子七正丁醇部位进行分离,所分离化合物运用核磁共振方法进行结构鉴定,应用MTT法测定分离化合物对体外培养人肿瘤细胞增殖的影响。结果从扣子七根茎正丁醇部位分离得到14个三萜皂苷,分别鉴定为竹节参皂苷IVa甲酯(1)、竹节参皂苷Ⅳa丁酯(2)、竹节参皂苷Ⅳ(3)、竹节参皂苷Ⅳa(4)、28-去糖竹节参皂苷Ⅳa(5)、齐墩果酸-3-O-β-D-(6′-甲酯)-吡喃葡萄糖醛酸苷(6)、(24R)-珠子参苷R1(7)、(24R)-拟人参皂苷F11(8)、(20S)-三七皂苷R2(9)、(20S)-人参皂苷Rg2(10)、人参皂苷Rg1(11)、人参皂苷Re(12)、人参皂苷Rd(13)、竹节参皂苷V甲酯(14)。活性研究结果显示,化合物5和6对胃癌BGC-823细胞、结肠癌HCT-116细胞、宫颈癌HeLa细胞及肝癌Hep G2细胞均显示了较强的活性,呈良好的剂量依赖关系,其中化合物5对BGC-823、HCT-116细胞的IC50分别为9.94、14.17μmol/L,化合物6对肝癌HepG2细胞的抑制作用最强(IC50=12.70μmol/L)。结论首次从扣子七中分离得到化合物6并报道了其光谱数据;其部分化学成分显示出抗肿瘤活性,其抗肿瘤活性与齐墩果烷型皂苷密切相关,且活性强弱可能与C-28取代基有关联,相关抗肿瘤机制值得进一步研究。Objective To study the active triterpenoid saponins of Tujia ethnomedicine Kouziqi(Panax japonicus var. major). The antitumor activity was screened and the relationship between the structure and activity of the compounds was discussed. Methods The ethanol extract of Kouziqi was isolated by Silica gel, ODS and MCI column chromatograph and purified by preparative HPLC. The structures were elucidated on the basis of spectroscopic analysis and compared with literatures. Using MTT assay to detect the cytotoxicity of 14 compounds in BGC-823, HCT-116, Hela, HepG-2 cells. Results A total of 14 known compounds were isolated from Tujia ethnomedicine Kouziqi and determined as chikusetsusaponin Ⅳa methyl ester(1), chikusetsusaponin Ⅳa butyl ester(2), chikusetsusaponin Ⅳ(3), chikusetsusaponin Ⅳa(4), 28-desglucosylchikusetsusaponin Ⅳa(5), oleanolic acid-3-O-β-D-(6’-methylester)-glucuronopyranoside(6),(24 R)-majonoside R1(7),(24 R)-pseudoginsinoside F11(8),(20 S)-notoginsinoside-R2(9),(20S)-ginsenoside Rg2(10), ginsenoside Rg1(11), ginsenoside Re(12), ginsenoside Rd(13) and chikusetsusaponin-V methyl ester(14). Among the 14 compounds, compounds 5 and 6 showed dose-dependent cytotoxicity to BGC-823, HCT-116, Hela and HepG-2 cells. Compound 5 had cytotoxicity in BGC-823 and HCT-116 cells with IC50 values of 9.94 and 14.17 μmol/L, respectively. Compound 6 had the best cytotoxicity in HepG-2 cells with IC50 value of 12.70 μmol/L. Conclusion Compound 6 is isolated from Kouziqi for the first time and its spectral data were reported. The antineoplastic activity of Tujia ethnomedicine Kouziqi is based on the oleanolic acid-type triterpenoid saponins and related to the substituents of C-28, but the mechanism still needs to be deeply studied.

关 键 词：土家族药物 扣子七 三萜皂苷 抗肿瘤活性 28-去糖竹节参皂苷Ⅳa 齐墩果酸-3-O-β-D-(6′-甲酯)-吡喃葡萄糖醛酸苷 

分 类 号：R284.1[医药卫生—中药学]