"Recycling preparative isolation of six bicyclol active metabolites from SD rat urine using macroporous resin, offline 2D LPLC/HPLC, and prep-HPLC combined with pharmacodynamic evaluation of two active metabolites"

作者全名："Huang, Xucong; Wu, Zhenghua; Qiaolongbatu, Xijier; Qu, Han; Ma, Cui; Xiang, Yujie; Jia, Mengqi; Liu, Yanchao; Wang, Shuowen; Jing, Lili; Jiang, Xinhui; Lou, Yuefen; Fan, Guorong"

作者地址："[Huang, Xucong; Lou, Yuefen] Tongji Univ, Shanghai Peoples Hosp 4, Dept Pharm, Sch Med, Shanghai 200434, Peoples R China; [Huang, Xucong; Xiang, Yujie; Jiang, Xinhui; Fan, Guorong] Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China; [Wu, Zhenghua; Ma, Cui; Jia, Mengqi; Liu, Yanchao; Wang, Shuowen; Fan, Guorong] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Clin Pharm, Sch Med, Shanghai 200080, Peoples R China; [Wu, Zhenghua; Qiaolongbatu, Xijier; Qu, Han; Wang, Shuowen; Jing, Lili; Fan, Guorong] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China"

通信作者："Lou, YF (通讯作者)，Tongji Univ, Shanghai Peoples Hosp 4, Dept Pharm, Sch Med, Shanghai 200434, Peoples R China.; Jiang, XH; Fan, GR (通讯作者)，Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China."

来源：ARABIAN JOURNAL OF CHEMISTRY

ESI学科分类：CHEMISTRY

WOS号：WOS:001045886800001

JCR分区：Q2

影响因子：5.3

年份：2023

卷号：16

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：Bicyclol; Metabolites; Offline 2D LPLC; HPLC; Recycling prep-HPLC; Liver injury zebrafish model

摘要："In our previous study, several bicyclol (BIC) metabolites were found to possess higher solubility, security, and efficacy than the parent drug. However, further research can't be conducted without monomeric metabolites. In the current study, a highly efficient preparative approach for six BIC-active metabolites from Sprague-Dawley (SD) rat urine was developed. First, 1000 mL of urine was purified and concentrated to 50 mL using microporous resin. Second, middle chromatogram isolated (MCI) GEL & REG;CHP20P adsorbent was used to create a low-pressure liquid chromatography (LPLC) column, which was combined with high-performance liquid chromatography (HPLC) to build an offline 2D system to visualize the separation process. Samples were segmented into 25 tubes and merged into three fractions. Then, recycling preparative HPLC was applied to the monomeric preparation to improve the efficiency. The prepared metabolites possessed high purity (greater than98%), and were verified by nuclear magnetic resonance (NMR). Finally, an isoniazid (INH)-induced liver injury zebrafish model was established to evaluate the efficiency of the BIC, M7, and M8 metabolites. The M7 metabolite exhibited a higher efficiency than BIC in histopathology, gene expression, and aminotransferase levels. Consequently, this study provided a strategy that inte-grating modern analytical techniques to prepare metabolites for discovering high value candidate compounds from biological metabolism.& COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)."

基金机构：National Natural Science Foundation of China [81793289]; Shanghai Key Clinical Discipline Construction Project [02. DY11.03.19.03]; Shanghai Songjiang District Science and technology research project [2020SJ277]; Special fund for clinical research of Wu Jieping Medical Foundation [320.6750.2021-2-75]; 2022 Bethune Quest -Pharmaceutical research capacity Building Program [Z04JKM202100]; Shanghai Sailing Program [21YF1436300]

基金资助正文：This work was supported by grants from the National Natural Science Foundation of China (81793289); Shanghai Key Clinical Discipline Construction Project (02. DY11.03.19.03); Shanghai Songjiang District Science and technology research project (2020SJ277); Special fund for clinical research of Wu Jieping Medical Foundation (320.6750.2021-2-75). 2022 Bethune Quest -Pharmaceutical research capacity Building Program(Z04JKM202100); Shanghai Sailing Program (21YF1436300).