Identification of in vitro and in vivo metabolites of alantolactone by UPLC-TOF-MS/MS

Donggui Yao, Zhe Li, Changhong Huo, Yufang Wang, Yibing Wu, Manli Zhang, Ligeng Li, Qingwen Shi, Hiromasa Kiyota, Xiaowei Shi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Alantolactone (AL), an active sesquiterpene originating from Inula helenium, is a potential anticancer and anti-inflammatory agent. However so far, studies on AL metabolism have not been reported. In the present study, we have investigated for the first time the in vivo and in vitro metabolites of AL using ultra performance liquid chromatography combined with time of flight mass spectrometry (UPLC-TOF-MS/MS). A unique on-line information-dependent acquisition (IDA) method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was applied to trace all of the probable metabolites of AL. Five MMDF templates were set according to the core structure of AL and the general metabolite biotransformation patterns, and other five sulfur-containing dimer filter templates were first established on the basis of structural elucidation of AL metabolites obtained from rat intestinal bacteria biotransformation. As a result, 44 metabolites were characterized: 41 metabolites from rat urine, bile and feces after oral administration of AL, and 13 metabolites from AL biotransformation by rat intestinal bacteria. Particularly, 26 metabolites were identified as novel sulfur-containing products. The results indicated that addition of double bond at Δ(11,13) and oxidization were the main metabolic reactions of AL. A new metabolism pathway to produce addition products of H2S to AL and further generate a series of sulfur-containing dimers of AL was revealed. This study significantly enriched our knowledge about AL metabolism, which will lead to a better understanding of the safety and efficacy of AL. At the same time, the established methodology can be widely applied for the structural determination of the metabolites of other sesquiterpene containing α-methylene-γ-lactone moiety.

Original languageEnglish
Pages (from-to)250-260
Number of pages11
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1033-1034
DOIs
Publication statusPublished - Oct 15 2016

Fingerprint

Metabolites
Biotransformation
Sulfur
Metabolism
Rats
Sesquiterpenes
Dimers
alantolactone
In Vitro Techniques
Bacteria
Inula
Defects
Liquid chromatography
Feces
Bile
Liquid Chromatography
Mass spectrometry
Oral Administration
Mass Spectrometry
Anti-Inflammatory Agents

Keywords

  • Alantolactone
  • Intestinal bacteria biotransformation
  • Metabolites
  • Multiple mass defect filter
  • UPLC-TOF-MS/MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Identification of in vitro and in vivo metabolites of alantolactone by UPLC-TOF-MS/MS. / Yao, Donggui; Li, Zhe; Huo, Changhong; Wang, Yufang; Wu, Yibing; Zhang, Manli; Li, Ligeng; Shi, Qingwen; Kiyota, Hiromasa; Shi, Xiaowei.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1033-1034, 15.10.2016, p. 250-260.

Research output: Contribution to journalArticle

Yao, Donggui ; Li, Zhe ; Huo, Changhong ; Wang, Yufang ; Wu, Yibing ; Zhang, Manli ; Li, Ligeng ; Shi, Qingwen ; Kiyota, Hiromasa ; Shi, Xiaowei. / Identification of in vitro and in vivo metabolites of alantolactone by UPLC-TOF-MS/MS. In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2016 ; Vol. 1033-1034. pp. 250-260.
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AU - Yao, Donggui

AU - Li, Zhe

AU - Huo, Changhong

AU - Wang, Yufang

AU - Wu, Yibing

AU - Zhang, Manli

AU - Li, Ligeng

AU - Shi, Qingwen

AU - Kiyota, Hiromasa

AU - Shi, Xiaowei

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AB - Alantolactone (AL), an active sesquiterpene originating from Inula helenium, is a potential anticancer and anti-inflammatory agent. However so far, studies on AL metabolism have not been reported. In the present study, we have investigated for the first time the in vivo and in vitro metabolites of AL using ultra performance liquid chromatography combined with time of flight mass spectrometry (UPLC-TOF-MS/MS). A unique on-line information-dependent acquisition (IDA) method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was applied to trace all of the probable metabolites of AL. Five MMDF templates were set according to the core structure of AL and the general metabolite biotransformation patterns, and other five sulfur-containing dimer filter templates were first established on the basis of structural elucidation of AL metabolites obtained from rat intestinal bacteria biotransformation. As a result, 44 metabolites were characterized: 41 metabolites from rat urine, bile and feces after oral administration of AL, and 13 metabolites from AL biotransformation by rat intestinal bacteria. Particularly, 26 metabolites were identified as novel sulfur-containing products. The results indicated that addition of double bond at Δ(11,13) and oxidization were the main metabolic reactions of AL. A new metabolism pathway to produce addition products of H2S to AL and further generate a series of sulfur-containing dimers of AL was revealed. This study significantly enriched our knowledge about AL metabolism, which will lead to a better understanding of the safety and efficacy of AL. At the same time, the established methodology can be widely applied for the structural determination of the metabolites of other sesquiterpene containing α-methylene-γ-lactone moiety.

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