Planta Med 2011; 77(15): 1712-1717
DOI: 10.1055/s-0030-1271063
Pharmakokinetic Investigations
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Metabolism of the Lignan Dehydrodiisoeugenol in Rats

Fei Li1 , 2 , Xiu-Wei Yang1
  • 1State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, China
  • 2Present address: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Further Information

Publication History

received February 21, 2011 revised April 2, 2011

accepted April 4, 2011

Publication Date:
03 May 2011 (eFirst)

Abstract

Dehydrodiisoeugenol (DDIE), a major active lignan from the seed and aril of the fruit of Myristica fragrans Houtt., functions as a potential anti-inflammatory agent by inhibiting lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages. However, the metabolism of DDIE remains unknown. This report describes the metabolic fate of DDIE in liver microsomes, urine, and feces of rats treated with DDIE. DDIE metabolites were isolated by sequential column chromatography and high-performance liquid chromatography from liver microsomes incubations, urine, and feces. Nine metabolites (M-1 to M-9), including 5 new metabolites, were determined spectroscopically using ultra-violet (UV), mass spectrometry (MS), nuclear magnetic resonance (NMR), and circular dichroism (CD). Analysis of the isolated metabolites showed that DDIE undergoes four major pathways of metabolism in the rat: oxidation (including hydroxylation, hydroformylation, and acetylation), demethylation, ring-opening, and dehydrogenation. In contrast to the metabolites from liver microsomes, the major metabolites in vivo were generated from DDIE by multiple metabolic reactions. Given these results, we describe a metabolic pathway for DDIE in the rat that gives insight into the metabolism of DDIE and the mechanism of DDIE bioactivity in humans.

References

Prof. Dr. Xiu-Wei Yang

State Key Laboratory of Natural and Biomimetic Drugs
Department of Natural Medicines
School of Pharmaceutical Sciences
Peking University

100191 Beijing

China

Phone: +86 10 82 80 51 06

Fax: +86 10 82 80 27 24

Email: xwyang@bjmu.edu.cn