title: Metabolism of the lignan dehydrodiisoeugenol in rats.
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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Yang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000652:urine; D005243:Feces / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D026323:Myristica / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry
chemical_list: D017705:Lignans; D010936:Plant Extracts; C496603:dehydrodiisoeugenol; D005054:Eugenol