枳椇子乙酸乙酯部位抗肿瘤活性成分筛选
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摘要
目的:研究筛选枳椇子Hovenia acerba Lindl.乙酸乙酯部位中具有抗肿瘤活性的化合物。方法:利用乙酸乙酯萃取枳椇子60%乙醇水提取物,并采用300～400目硅胶与制备级HPLC对其萃取物进行分离纯化,最终得到4个化合物,通过MTT法筛选发现其中ZJZ-Z2具有最优的活性,通过ESI-MS、~1H-NMR和~(13)C-NMR检测,并通过与相关文献对比,初步推测该化合物为二氢杨梅素(dihydromyricelin),体内实验证明ZJZ-Z2具有体内抗肿瘤活性。结果:通过MTT法分别对枳椇子乙酸乙酯部位硅胶分离得到的12个组分进行测定,发现其中第4组分对肿瘤细胞Huh-7、OS-RC-2的半数抑制率(IC_(50))分别为70.4、69.8μg·mL~(-1);进一步分离纯化得到的ZJZ-Z2对肿瘤细胞OS-RC-2、Huh-7、HCT-116、CFPAC-1的IC_(50)分别为33.8、63.9、46.8、55.1μg·mL~(-1),且对H22荷瘤小鼠模型表现出一定的抑瘤作用。结论:枳椇子乙酸乙酯部位具有抗肿瘤活性,其主要的抗肿瘤活性成分为二氢杨梅素。
Objective:To study the anti-tumor activity constituents in the ethyl acetate extract of Hovenia acerba.Methods:60% ethanol aqueous extract of H.acerba was extracted with ethyl acetate and purified with 300-400 mesh silica gel and preparative grade HPLC.The chemical structures of the isolated compounds were determined by ESI-MS,~1H-NMR and ~(13)C-NMR.Results:Twelve components were isolated from the ethyl acetate fraction of H.acerba.Four compounds were obtained and found that ZJZ-Z2 had the best activity.The compounds were dihydromyricelin.The in vivo experiments showed that ZJZ-Z2 had antitumor activity.By MTT method,IC_(50) of the fourth component to Huh-7 and OS-RC-2 was 70.4 μg·mL~(-1) and 69.8 μg·mL~(-1) Further separation and purification to obtain ZJZ-Z2,which half-inhibition rate(IC_(50))to tumor cells OS-RC-2,Huh-7,HCT-116,CFPAC-1 was 33.8 μg·mL~(-1),63.9 μg·mL~(-1),46.8 μg·mL~(-1),55.1 μg·mL~(-1),and it is found that they had a certain anti-tumor effect to H22 tumor-bearing model mice.Conclusion:The ethyl acetate fraction of H.acerba has antitumor activity,and the main active ingredient is dihydromyricetin.
Objective:To study the anti-tumor activity constituents in the ethyl acetate extract of Hovenia acerba.Methods:60% ethanol aqueous extract of H.acerba was extracted with ethyl acetate and purified with 300-400 mesh silica gel and preparative grade HPLC.The chemical structures of the isolated compounds were determined by ESI-MS,~1H-NMR and ~(13)C-NMR.Results:Twelve components were isolated from the ethyl acetate fraction of H.acerba.Four compounds were obtained and found that ZJZ-Z2 had the best activity.The compounds were dihydromyricelin.The in vivo experiments showed that ZJZ-Z2 had antitumor activity.By MTT method,IC_(50) of the fourth component to Huh-7 and OS-RC-2 was 70.4 μg·mL~(-1) and 69.8 μg·mL~(-1) Further separation and purification to obtain ZJZ-Z2,which half-inhibition rate(IC_(50))to tumor cells OS-RC-2,Huh-7,HCT-116,CFPAC-1 was 33.8 μg·mL~(-1),63.9 μg·mL~(-1),46.8 μg·mL~(-1),55.1 μg·mL~(-1),and it is found that they had a certain anti-tumor effect to H22 tumor-bearing model mice.Conclusion:The ethyl acetate fraction of H.acerba has antitumor activity,and the main active ingredient is dihydromyricetin.
引文
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[2] 余选良,朱肖鸿,冯舒婷.枳椇子治疗酒精性肝病现状[J].浙江中西医结合杂志,2017,27(4):342-344.
[3] 蔡冰洁.枳椇多糖的理化性质及生物活性研究[D].合肥:合肥工业大学,2017.
[4] 罗千古,陶莉.枳椇子的药理作用和临床应用研究[J].中国中医药咨讯,2012,4(3):265.
[5] 叶文斌,樊亮,王昱,等.拐枣多糖对糖尿病小鼠血糖血脂的影响[J].现代食品科技,2016,32(1):6-12.
[6] 嵇扬.枳椇子水提取物细胞毒作用与抑瘤功效的研究[J].中华中医药学刊,2003,21(4):538-538.
[7] AMMAR R B,NEFFATI A,SKANDRANI I,et al.Anti-lipid peroxidation and induction of apoptosis in the erythroleukaemic cell line K562 by extracts from(Tunisian)Rhamnus alaternus L.(Rhamnaceae)[J].Nat Prod Res,2011,25(11):1047-1058.
[8] 王旭,陈绍红,钟赣生,等.葛花、枳椇子配伍对慢性酒精性肝损伤大鼠海马7种单胺类神经递质及代谢产物含量水平的影响[J].中国现代中药,2016,18(5):558-562.
[9] 柳海艳,钟赣生,王茜,等.葛花枳椇子及其配伍采用水提和醇提对酒精性肝损伤大鼠肝脏功能的影响[J].科技导报,2012,30(增刊1):65-70.
[10] 王楠,杜双奎,冯宪超,等.枳椇乳酸菌发酵饮料对小鼠酒精肝损伤的保护作用[J].现代食品科技,2016,32(8):28-33.
[11] 张奇.枳椇子抗肿瘤活性化合物SIPI-ZQ2的分离、纯化及其体内、外抗肿瘤活性评价和急性毒性研究[D].上海:上海医药工业研究院,2017.
[12] 徐方方.枳椇子的化学成分研究[D].广州:暨南大学,2011.
[13] 晋海洋.枳椇子化学成分的研究[D].长春:吉林大学,2015.
[14] 谢蓉蓉,张德志,庞小雄,等.枳椇子乙酸乙酯部位化学成分的研究[J].亚太传统医药,2012,8(9):27-28.
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