UPLC-QTOF-MS Based Comparison of Rotundic Acid Metabolic Profiles in Normal and NAFLD Rats

被引:1
作者
Wu, Lvying [1 ]
Xing, Lei [1 ]
Zou, Yake [1 ]
Wang, Zichen [1 ]
Gou, Yuanyuan [1 ]
Zhang, Lei [1 ]
Guan, Su [1 ,2 ]
机构
[1] South China Univ Technol, Sch Biol & Biol Engn, MOE Joint Int Res Lab Synthet Biol & Med, Guangzhou 510006, Peoples R China
[2] Guangdong Prov Key Lab New Drug Design & Evaluat, Guangzhou 510407, Peoples R China
关键词
metabolite; NAFLD; rats; rotundic acid; UPLC-QTOF-MS; PERFORMANCE LIQUID-CHROMATOGRAPHY; FATTY LIVER-DISEASE; MADECASSIC ACID; IDENTIFICATION; TRITERPENOIDS; CYTOTOXICITY; MS/MS;
D O I
10.3390/metabo13010038
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rotundic acid, the principal bioactive constituent of the herbal remedy "Jiubiying", has been considered as a candidate compound for treating non-alcoholic fatty liver disease (NAFLD). However, the in vivo and in vitro metabolism of rotundic acid has remained unclear. With the aim of elucidating its metabolic profile, a reliable approach that used ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was applied for screening and identifying rotundic acid in vivo (plasma, feces, urine, and liver tissue of normal and NAFLD model rats) and in vitro (rat liver microsomes) metabolites. Herein, 26 metabolites of rotundic acid were identified, including 22 metabolites in normal rats, 20 metabolites in NAFLD model rats, and eight metabolites in rat liver microsomes. Among them, 17 metabolites were identified for the first time. These data illustrate that the pathological status of NAFLD affects the metabolism of rotundic acid. Furthermore, the major pathways of metabolism included phase I (demethylation, desaturation, etc.) and phase II (sulfation and glucuronidation) reactions, as well as a combined multiple-step metabolism. This work provides important information on the metabolism of rotundic acid and lays the foundation for its future clinical application.
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页数:15
相关论文
共 33 条
[1]   Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders [J].
Aron-Wisnewsky, Judith ;
Vigliotti, Chloe ;
Witjes, Julia ;
Le, Phuong ;
Holleboom, Adriaan G. ;
Verheij, Joanne ;
Nieuwdorp, Max ;
Clement, Karine .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2020, 17 (05) :279-297
[2]   Simultaneous Qualitative and Quantitative Analyses of Triterpenoids in Ilex pubescens by Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry [J].
Cao, Di ;
Wang, Qing ;
Jin, Jing ;
Qiu, Maosong ;
Zhou, Lian ;
Zhou, Xinghong ;
Li, Hui ;
Zhao, Zhongxiang .
PHYTOCHEMICAL ANALYSIS, 2018, 29 (02) :168-179
[3]   Advancing the understanding of NAFLD to hepatocellular carcinoma development: From experimental models to humans [J].
Chen, Kan ;
Ma, Jianbo ;
Jia, Xiaoyuan ;
Ai, Wen ;
Ma, Zhongren ;
Pan, Qiuwei .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2019, 1871 (01) :117-125
[4]  
Chen S., 2010, Patent No. 101849950
[5]   Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters [J].
Cobbina, Enoch ;
Akhlaghi, Fatemeh .
DRUG METABOLISM REVIEWS, 2017, 49 (02) :197-211
[6]   Antiplatelet aggregation triterpene saponins from the barks of Ilex rotunda [J].
Fan, Zhen ;
Zhou, Lian ;
Xiong, Tianqin ;
Zhou, Jinsong ;
Li, Qingguo ;
Tan, Qinglong ;
Zhao, Zhongxiang ;
Jin, Jing .
FITOTERAPIA, 2015, 101 :19-26
[7]   Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation [J].
Farzanegi, Parvin ;
Dana, Amir ;
Ebrahimpoor, Zeynab ;
Asadi, Mahdieh ;
Azarbayjani, Mohammad Ali .
EUROPEAN JOURNAL OF SPORT SCIENCE, 2019, 19 (07) :994-1003
[8]   Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry [J].
Guan, Su ;
Zou, Yake ;
Jia, Bingjie ;
Wu, Lvying ;
Yang, Zhicheng ;
Yuan, Fang ;
Zhang, Lei .
JOURNAL OF SEPARATION SCIENCE, 2018, 41 (24) :4469-4479
[9]   Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives [J].
He, Yu-Fang ;
Nan, Min-Lun ;
Sun, Jia-Ming ;
Meng, Zhao-Jie ;
Li, Wei ;
Zhang, Ming .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (09) :2543-2547
[10]   Synthesis, Characterization and Cytotoxicity of New Rotundic Acid Derivatives [J].
He, Yu-Fang ;
Nan, Min-Lun ;
Sun, Jia-Ming ;
Meng, Zhao-Jie ;
Yue, Fa-Gui ;
Zhao, Quan-Cheng ;
Yang, Xiao-Hong ;
Wang, Hui .
MOLECULES, 2012, 17 (02) :1278-1291