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  3. Metabolic profiling of dehydrodiisoeugenol using xenobiotic metabolomics

Metabolic profiling of dehydrodiisoeugenol using xenobiotic metabolomics

  • J Pharm Biomed Anal. 2017 Oct 25;145:725-733. doi: 10.1016/j.jpba.2017.07.045.
Qian-Qian Lv 1,  Xiao-Nan Yang 2,  Dong-Mei Yan 3,  Wei-Qing Liang 4,  Hong-Ning Liu 5,  Xiu-Wei Yang 6,  Fei Li 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
  • 3 School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
  • 4 Center for Medicinal Resources Research, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, 310007, China. Electronic address: jxlwq22@163.com.
  • 5 Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
  • 6 School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing, 100191, China.
  • 7 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China. Electronic address: lifeib@mail.kib.ac.cn.
PMID: 28806569 DOI: 10.1016/j.jpba.2017.07.045
Abstract

Dehydrodiisoeugenol (DDIE), a representative and major benzofuran-type neolignan in Myristica fragrans Houtt., shows anti-inflammatory and anti-bacterial actions. In order to better understand its pharmacological properties, xenobiotic metabolomics was used to determine the metabolic map of DDIE and its influence on endogenous metabolites. Total thirteen metabolites of DDIE were identified through in vivo and in vitro metabolism, and seven of them were reported for the first time in the present study. The identity of DDIE metabolites was achieved by comparison of the MS/MS fragmentation pattern with DDIE using ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI- QTOFMS). Demethylation and ring-opening reaction were the major metabolic pathways for in vivo metabolism of DDIE. Recombinant cytochrome P450s (CYPs) screening revealed that CYP1A1 is a primary Enzyme contributing to the formation of metabolites D1-D4. More importantly, the levels of two endogenous metabolites 2,8-dihydroxyquinoline and its glucuronide were significantly elevated in mouse urine after DDIE exposure, which explains in part its modulatory effects on gut microbiota. Taken together, these data contribute to the understanding of the disposition and pharmacological activities of DDIE in vivo.

Keywords

Dehydrodiisoeugenol; Metabolic profiling; UPLC-ESI-QTOFMS; Xenobiotic metabolomics.

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