摘要
目的发现雷公藤多苷片抗不同亚型血液肿瘤的敏感细胞株及其对敏感细胞株增殖抑制作用的物质基础。方法利用CCK-8法检测雷公藤多苷片及其提取物体外对肿瘤细胞增殖的影响;构建敏感瘤株的体内异种移植瘤动物模型考察雷公藤多苷片对肿瘤细胞的抑制作用;采用色谱分离技术对雷公藤多苷片提取物进行系统分离,综合质谱和核磁共振数据鉴定化合物结构,并考察单体化合物抗人急性单核细胞白血病(Acute monocytic leukemia,AMOL)活性;进一步通过制备液相定向敲除雷公藤多苷片及其提取物中的雷公藤甲素(Triptolide,TP),考察敲除TP前后雷公藤多苷片及其提取物的抗AMOL活性。结果细胞实验结果表明雷公藤多苷片有较强的抗AMOL活性;体内异种移植瘤实验结果表明雷公藤多苷片可明显抑制AMOL细胞皮下异种移植瘤的生长;进一步对雷公藤多苷片提取物进行系统分离及其细胞水平上的活性评价,发现二萜类化合物TP抗AMOL活性最强;定向敲除TP后的雷公藤多苷片及其提取物对AMOL细胞MV-4-11的IC_(50)值分别升高8及13倍。结论雷公藤多苷片对AMOL细胞具有显著的抗白血病效应,其中TP是其发挥药效的物质基础。
OBJECTIVE To discovery sensitive cell lines of tripterygium glycosides tablet against different subtypes of hematological tumors,and to find out the material base for the effect on proliferative inhibition against sensitive cell lines.METHODS The CCK-8 assay was used to assess the effect of tripterygium glycosides tablet and its extract on cell proliferation in vitro;Then,the in vivo subcutaneous xenograft models by injecting sensitive cells were constructed to test the inhibitory activity of tripterygium glycosides tablet;Furthermore,the extract of tripterygium glycosides was systemically chemical investigated by chromatographic separation techniques,mass spectrometry,and nuclear magnetic resonance,and anti-human acute monocytic leukemia(AMOL)activity was tested for each compound;In the end,preparative HPLC was used for the specific removal of triptolide(TP)from the extract of tripterygium glycosides.The anti-AMOL activity was measured and analyzed after removing TP from the formulations of T.wilfordii.RESULTS The results of cell experiments indicated that tripterygium glycosides exhibited potent anti-AMOL activity;Next,in vivo tumor xenograft models showed tripterygium glycosides significantly inhibited the growth of subcutaneous tumor xenografts of AMOL cells;Furthermore,chemical constituents of tripterygium glycosides extract were isolated systemically,the activity were evaluated at the cellular level.It was found that TP showed the strongest anti-AMOL activity.Finally,it was found that the IC_(50) values of the tripterygium glycosides tablet and its extract against AMOL cells increased 8 and 13 fold,respectively,after removing TP.CONCLUSION Tripterygium glycosides tablet shows significant inhibitory activity against acute monocytic leukemia cells,and its diterpenoid,triptolide,is the most active ingredient.
作者
方冰倩
王亚楠
刘琰
王吓长
康迪
胡立宏
FANG Bing-qian;WANG Ya-nan;LIU Yan;WANG Xia-chang;KANG Di;HU Li-hong(School of Pharmacy,Jiangsu Key Laboratory for Functional Substances of Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China)
出处
《南京中医药大学学报》
CAS
CSCD
北大核心
2022年第9期748-760,共13页
Journal of Nanjing University of Traditional Chinese Medicine
基金
国家重点研发计划(2018YFC1707900)
国家自然科学基金青年科学基金项目(82104270)
江苏省研究生实践创新计划项目(KYCX22_2035)。
关键词
雷公藤多苷片
化学成分
人急性单核细胞白血病
雷公藤甲素
抗肿瘤
tripterygium glycosides tablet
chemical constituents
human acute monocytic leukemia
triptolide
antineoplasm
