Abstract
Curcumol is one of the major components of the essential oil of Curcuma wenyujin with the structure of a guaiane-type sesquiterpenoid hemiketal. It exhibits clear antitumor, antihepatic fibrosis, antioxidant, and antimicrobial activities. In this article, the metabolism of curcumol in rats was investigated by characterizing metabolites excreted into urine. Sixteen phase 1 metabolites of curcumol were isolated from the urine of rats after an oral dose of 40 mg/kg, and their structures were elucidated on the basis of spectroscopic data. The metabolites were characterized as 2α-hydroxycurcumol (M-1), (11αH)-3α-hydroxy-9-en-8,13-epoxycurcumol (M-2), (11αH)-14-hydroxy-9-en-8,13-epoxycurcumol (M-3), (11βH)-14-hydroxy-9-en-8,12-epoxycurcumol (M-4), 10α,14-dihydroxy-(1αH,7βH)-guai-4-en-3,8-dione (M-5), 10β,14-dihydroxy-(1αH,7βH)-guai-4-en-3,8-dione (M-6), 10β-hydroxy-(1αH,7βH,11αH)-guai-8(13),8(14)-diepoxy-4-en-3-one (M-7), 10β-hydroxy-(1αH,7βH,11βH)-guai-8(12),8(14)-diepoxy-4-en-3-one (M-8), 10α-hydroxy-(1αH,7βH,11αH)-guai-8(13), 8(14)-diepoxy-4-en-3-one (M-9), 10α-hydroxy-(1αH,7βH,11βH)-guai-8(12),8(14)-diepoxy-4-en-3-one (M-10), 10α,14,15-trihydroxy-(1αH,7βH)-guai-4-en-3,8-dione (M-11), 10β-hydroxy-(1αH,7βH)-guai-4-en-3,8-dioxo-13-oic acid (M-12), (1αH,7βH)-guai-4,10(14)-dien-3, 8-dioxo-13-oic acid (M-13), 5β,10β-dihydroxy-(1αH,7βH,11αH)-guai-8(13),8(14)-diepoxide (M-14), 10β,14-dihydroxycurcumol (M-15), and 5β,10β,14-trihydroxy-(1αH,7βH)-guai-8-one (M-16). All were newly identified compounds, among which M-3 and M-4, M-5 and M-6, and M-7, M-8, M-9, and M-10 are three groups of epimers. On the basis of the metabolite profile, the possible metabolic pathways of curcumol in rats are proposed. This is the first study of the metabolites of guaiane-type sesquiterpene in animals.
Footnotes
This work was supported by the National Natural Science Foundation of China [Grant 30973630]; and the Liaoning Natural Science Foundation [Grant 20062057].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.110.034215.
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ABBREVIATIONS:
- HPLC
- high-performance liquid chromatography
- HMQC
- heteronuclear multiple-quantum correlation
- HMBC
- heteronuclear multiple-bond correlation
- NOESY
- nuclear Overhauser effect spectroscopy
- ESI-MS
- electrospray ionization-mass spectrometry
- HRFAB-MS
- high-resolution fast atom bombardment-mass spectrometry
- EtOAc
- ethyl acetate
- TLC
- thin-layer chromatography
- MeOH
- methanol
- EtOH
- ethanol
- OH
- hydroxy
- LC-MS
- liquid chromatography-mass spectrometry.
- Received May 4, 2010.
- Accepted August 3, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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