表面活性剂对姜黄素类成分水溶性与抗肝纤维化作用的影响  

Effects of surfactants on water solubility and anti-hepatic fibrosis of curcuminoids

作　　者：刘芳 张倩[1,2] 李锐 肖洪涛[3] 邝婷婷 欧阳雪倩[4] 殷恒福[4] LIU Fang;ZHANG Qian;LI Rui;XIAO Hong-tao;KUANG Ting-ting;OUYANG Xue-qian;YIN Heng-fu(School of Food and Bioengineering, Xihua University, Chengdu 610039, China;Huaian Applied Technology Research Center, Xihua University, Huaian 223001, China;Department of Pharmacy, Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People＇s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China;National Institute of Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China)

机构地区：[1]西华大学食品与生物工程学院,四川成都610039 [2]西华大学淮安应用技术研究中心,江苏淮安223001 [3]电子科技大学附属医院四川省人民医院药学部,四川成都610072 [4]成都中医药大学民族医药学院,四川成都611130

出　　处：《中草药》2018年第8期1809-1815,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81302742);淮安市重点研发项目(HAN201622);四川省教育厅重点项目(11ZA005)

摘　　要：目的研究以3种食品级表面活性剂为增溶剂增加姜黄素类成分的水溶性,并研究表面活性剂对姜黄素类成分结构、稳定性及体内抗肝纤维化作用的影响。方法采用高速分散法制备姜黄素类成分与表面活性剂的配比溶液,通过LC-MS/MS对配比溶液中姜黄素类成分进行定性分析,建立HPLC-DAD指纹图谱,进行定量分析;进一步通过肝纤维化大鼠模型评估不同质量浓度姜黄素配比溶液的抗肝纤维化作用。结果羟乙基纤维素、明胶、蔗糖酯加入的质量比为3∶5∶40,高速分散机转速为6 000 r/min时,姜黄素类成分的水溶性最大为1.387 mg/m L;LC-MS/MS分析表明,姜黄素类成分结构未改变;指纹图谱表明,有18批次样品相似度大于99%;且不同批次样品中姜黄素、脱甲氧基姜黄素、双脱甲氧基姜黄素含量稳定,RSD分别为1.60%、2.24%、3.74%;抗肝纤维化动物实验表明,游离药物混悬液组大鼠天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)水平分别为(64.1±20.3)、(45.1±13.9)U/L,而姜黄素配比溶液组为(19.4±8.7)、(11.8±4.9)U/L。结论姜黄素类成分经表面活性剂配比增溶后水溶性较游离状态(2.677μg/m L)提高了517倍,重复试验表明姜黄素类成分的化学结构与含量均稳定;增溶后的姜黄素类成分显示出更好的抗肝纤维化效果。Objective To increase the water solubility of curcumin constituents by three kinds of food grade surfactants, and to study the effect of surfactants on the quality standard and stability and anti-hepatic fibrosis in vivo of curcumin solution. Methods The high-speed dispersion method was used to prepare the solution of curcuminoids-surfactants. The qualitative analysis of curcuminoids was confirmed by LC-MS/MS. HPLC-DAD fingerprinting was established and quantitative analysis was conducted. And the effects on anti-liver fibrosis of different concentrations curcumin ratio solution were evaluated by rat model. Results The maximum water solubility of curcumin constituents was 1.387 mg/m L. LC-MS/MS analysis showed that the structure of curcuminoids were stable; The results of fingerprinting analysis demonstrated that the similarity of 18 batches of samples were higher than 99%. The contents of curcumin, demethoxycurcumin and bisdemethoxycurcumin in different batches of samples were stable with the RSD of 1.60%, 2.24%, and 3.74%. The rat model of hepatic fibrosis showed that the contents of AST and ALT in free curcumin suspension group were（64.1 ± 20.3） and（45.1 ± 13.9） U/L, respectively, while that solution of curcuminoids-surfactants group was（19.4 ± 8.7） and（11.8 ± 4.9） U/L. Conclusion The solubility of curcuminoids was increased 517 times compared with the free state（2.677 μg/m L） after solubilization with surfactants, and repeated tests indicated that the structure and contents of curcuminoids were stable; the solubilized curcuminoids exhibited better anti-liver fibrosis effects than the free.

关 键 词：姜黄素类成分 表面活性剂 水溶性 定性 定量 抗肝纤维化 

分 类 号：R283.6[医药卫生—中药学]