吴茱萸水煎液肝毒质量标志物确认研究  

Confirmation study of hepatotoxic quality marker in Euodiae Fructus decoction

作　　者：王亮[1] 孙凯滨 吴晓文[1] 孙蓉 WANG Liang;SUN Kai-bin;WU Xiao-wen;SUN Rong(Shandong Academy of Chinese Medicine,Jinan 250014,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Second Hospital of Shandong University,Jinan 250033,China;School of Advanced Medical Science,Shandong University,Jinan 250012,China)

机构地区：[1]山东省中医药研究院,山东济南250014 [2]山东中医药大学,山东济南250355 [3]山东大学第二医院,山东济南250033 [4]山东大学高等医学研究院,山东济南250012

出　　处：《中草药》2019年第19期4547-4555,共9页Chinese Traditional and Herbal Drugs

基　　金：国家重点基础研究发展计划“973”中医基础理论专项资助项目课题2(2009CB522802);山东省中医药科技发展计划(2013-120);山东省重大科技创新工程(2017CXGC1308);山东省自然科学基金青年基金(ZR2016HQ17);泰山学者工程专项经费资助(Ns201511107)

摘　　要：目的对吴茱萸水煎液的肝毒质量标志物(Q-marker)进行确认研究。方法通过体外肝毒性指标和流式细胞分析对目标化合物的肝毒性进行初步研究,通过网络药理学对其作用靶点和靶器官进行预测,通过LC-MS对目标化合物3-O-反式-咖啡酰葡萄糖酸(1)、4-O-反式-咖啡酰葡萄糖酸(2)、2-O-反式-咖啡酰葡萄糖酸(3)的吸收入血情况进行定性分析,通过Q-marker属性的系统研究,对吴茱萸水煎液的肝毒Q-marker进行确认。结果化合物1、2、3主要通过直接毒性影响肝脏L02细胞的活力和G0/G1期的阻滞作用影响L02细胞的增殖,从而产生肝毒性;网络药理学分析结果表明作用的靶器官可能为肝脏;给药后化合物1、2、3可以原型形式吸收入血;化合物1、2、3具有结构确认、毒性确认、可测性、传递性的特点,可能不具有专属性。结论化合物1、2、3可确认为吴茱萸水煎液的肝毒Q-marker。Objective To confirm the hepatotoxic Q-marker of Euodiae Fructus decoction. Methods The hepatotoxicity of target compounds was studied by hepatotoxicity index and flow cytometry. The targets and target organs were predicted by network pharmacology. The qualitative absorption analysis of 3-O-trans-caffeoylgluconic acid(1), 4-O-trans-caffeoylgluconic acid(2), 2-O-trans-caffeoylgluconic acid(3) was performed by LC-MS. Through the systematic study of Q-marker properties, the confirmation study of hepatotoxicity Q-marker in Euodiae Fructus decoction was performed. Results Compounds 1, 2, and 3 inhibited the growth of L02 cells in G0/G1 phase and had direct toxicity to L02 cells, which led to hepatotoxicity. The target organ may be the liver by the network pharmacology analysis. After drug administration, compounds 1, 2, and 3 could be absorbed into the blood by prototype. Compounds 1, 2, and 3 had properties of structural confirmation, toxicity confirmation, measurability, and transmissibility. Conclusion Compounds 1, 2, and 3 could be confirmed as hepatotoxic Q-marker of Euodiae Fructus decoction.

关 键 词：吴茱萸 肝毒质量标志物 入血分析 网络药理学 可测性 传递性 3-O-反式-咖啡酰葡萄糖酸 4-O-反式-咖啡酰葡萄糖酸 2-O-反式-咖啡酰葡萄糖酸 

分 类 号：R285.5[医药卫生—中药学]