中国中药杂志

2019, v.44(21) 4704-4712

[打印本页] [关闭]
本期目录(Current Issue) | 过刊浏览(Past Issue) | 高级检索(Advanced Search)

迷迭香酸的大鼠体内代谢产物及代谢途径分析
Profiling and identification of in vivo metabolism of rosmarinic acid in rats

郭少波;徐露露;蒋丽娟;王菲;王子健;张加余;刘斌;
GUO Shao-bo;XU Lu-lu;JIANG Li-juan;WANG Fei;WANG Zi-jian;ZHANG Jia-yu;LIU Bin;School of Chinese Pharmacy,Beijing University of Chinese Medicine;People's Hospital of Peking University;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine;

摘要(Abstract):

迷迭香酸是薄荷、丹参、迷迭香、紫苏等中药的有效成分。目前对迷迭香酸的体内代谢过程和代谢产物尚不明确,该研究对迷迭香酸在大鼠体内的代谢进行分析。采用UHPLC-LTQ-OrbitrapHRMS对迷迭香酸在大鼠体内的代谢产物和代谢途径进行分析。大鼠灌胃给药后,收集大鼠血浆、尿液和粪便样品。经固相萃取法处理生物样品后,采用Acquity UPLCBEH C18色谱柱(2. 1 mm×100 mm,1. 7μm),以0. 1%甲酸水溶液(A)-乙腈(B)为流动相,梯度洗脱,流速0. 30 m L·min-1,柱温35℃。在正负离子模式下对比含药血浆、尿液、粪便及对应的空白组样品进行分析。通过分析高分辨质谱提供的准分子离子峰和碎片离子信息,结合对照品与文献报道结果,共从大鼠生物样品中筛选鉴定了包括原型在内的36个代谢产物,主要代谢途径为迷迭香酸分解为小分子化合物(反式咖啡酸、香豆酸、间羟基苯甲酸和丹参素)后进一步发生硫酸酯化、甲基化、葡萄糖醛酸结合和葡萄糖结合等反应。结果表明,应用UHPLC-LTQ-Orbitrap高分辨液质联用技术可较全面地阐明迷迭香酸在大鼠体内的代谢产物和代谢途径,为进一步的药效学和毒理学研究提供借鉴。
Rosmarinic acid,a hydrosoluble polyphenolic hydroxyl compound,is the active ingredient in such traditional Chinese medicines as Menthae Haplocalycis Herba,Salviae Miltiorrhizae Radix et Rhizoma,Rosemary,Perillae Folium. Because of its good anti-inflammatory,anti-oxidant and anti-tumor effects,it is widely used in food,medicine and other fields. However,the metabolic process and metabolites of rosmarinic acid in vivo have not been completely defined. In this study,an efficient method of ultra-high performance liquid chromatography combined with linear ion trap-Orbitrap(UHPLC-LTQ-Orbitrap) mass spectrometer was used to analyze the metabolites in vivo of rosmarinic acid in rats. Plasma,urine and feces samples were collected after oral administration of rosmarinic acid. After biological samples were processed by solid phase extraction,Acquity UPLC  BEH C18 column(2. 1 mm × 100 mm,1. 7 μm) was used with 0. 1% formic acid(A)-acetonitrile(B) solution as the mobile phase at the speed of 0. 30 m L·min-1 and temperature of 35 ℃ under gradient conditions. The plasma,urine,feces and the blank samples were then analyzed by ESI-LTQ-Orbitrap under both negative and positive ion modes. Based on the accurate mass measurement(<5),MS/MS fragmentation patterns,standards and literatures,a total of 36 metabolites were screened out and identified in the biological samples collected from rats after intragastric administration. Three were identified 3 from rat plasma,31 from urine,and 7 from feces. The main metabolic pathways of rosmarinic acid in rats can be divided into five parts. Rosmarinic acid were first decomposed into small molecules,such as trans-caffeic acid,coumaric acid,m-hydroxybenzoic acid and Danshensu,which were followed by sulfation,methylation,glucuronic acid conjugation and glucose conjugation. The results showed that UHPLC-LTQ-Orbitrap mass spectrometer could be used to analyze the metabolism of rosmarinic acid in rats,and provide reference for further studies on toxicology,pharmacodynamics and secondary development of Chinese medicine.

关键词(KeyWords): UHPLC-LTQ-Orbitrap;迷迭香酸;代谢产物;代谢途径
UHPLC-LTQ-Orbitrap;rosmarinic acid;metabolites;metabolic pathways

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81173520);; 江苏省中药药效与安全性评价重点实验室项目(JKLPSE201816);; 中医脑病学山西省重点实验室(山西中医药大学)项目(CME-OP-2017002)

作者(Authors): 郭少波;徐露露;蒋丽娟;王菲;王子健;张加余;刘斌;
GUO Shao-bo;XU Lu-lu;JIANG Li-juan;WANG Fei;WANG Zi-jian;ZHANG Jia-yu;LIU Bin;School of Chinese Pharmacy,Beijing University of Chinese Medicine;People's Hospital of Peking University;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine;

DOI: 10.19540/j.cnki.cjcmm.20190314.001

参考文献(References):

扩展功能
本文信息
服务与反馈
本文关键词相关文章
本文作者相关文章
中国知网
分享