Abstract
Metabolic research for herbal medicine (HM) is a formidable task, which is still in its infancy due to complicated components in HM, complex metabolic pathways, and lack of authentic standards. The present work contributes to the development of a powerful technical platform to rapidly identify and classify metabolites of herbal components based on a liquid chromatography hybrid ion trap time-of-flight mass spectrometry. Taking Schisandra lignans extract as an example, the metabolic studies were completed both in vitro and in vivo. In the in vitro study, metabolites for five representative Schisandra lignans were identified and structurally characterized. The major metabolic pathways were summed as demethylation, hydroxylation, and demethylation and hydroxylation. In the in vivo study, 44 metabolites were detected in rat urine. These metabolites were identified and classified rapidly according to the metabolic rules obtained in the in vitro studies, and hydroxylation was confirmed as the primacy metabolic pathway for lignans in rat urine. In addition, “relative cumulative excretion” (RCE) for the metabolites in female and male rats were calculated according to their relative intensities in the urine samples collected at 0 to 12, 12 to 24, and 24 to 36 h. As a result, great gender-related difference on RCE was observed. For most metabolites, RCE in female rats was significantly lower than that in male rats. In conclusion, the presently developed methodology and approach on metabolic research for Schisandra lignans will find its wide use in metabolic studies for herbal medicines.
Footnotes
This work was supported in part by the National Natural Science Foundation of China [Grants 30801422, 30630076]; the Natural Science Foundation of Jiangsu Province [Grant BK2008038]; and the National Key New Drug Creation Special Programme [Grants 2009ZX09304-001, 2009ZX09502-004].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.110.033373.
↵ The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
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ABBREVIATIONS:
- HM
- herbal medicine
- HPLC
- high-performance liquid chromatography
- MS
- mass spectrometry
- IT-TOF/MS
- hybrid ion trap and time-of-flight mass spectrometry
- LC-IT-TOF/MS
- liquid chromatography-hybrid ion trap and time-of-flight mass spectrometry
- SLE
- Schisandra lignans extract
- RCE
- relative cumulative excretion
- EICs
- extracted ion chromatograms
- LC-ESI-IT-TOF/MS
- liquid chromatography electrospray ionization hybrid ion trap and time-of-flight mass spectrometry
- GEM
- gradient elution mode
- CID
- collision-induced dissociation
- UDPGA
- UDP-glucuronic acid
- P450
- cytochromes P450.
- Received March 18, 2010.
- Accepted July 13, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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