Isolation and identification of phase 1 metabolites of curcumol in rats.

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), (11ßH)-14-hydroxy-9-en-8,12-epoxycurcumol (M-4), 10α,14-dihydroxy-(1αH,7ßH)-guai-4-en-3,8-dione (M-5), 10ß,14-dihydroxy-(1αH,7ßH)-guai-4-en-3,8-dione (M-6), 10ß-hydroxy-(1αH,7ßH,11αH)-guai-8(13),8(14)-diepoxy-4-en-3-one (M-7), 10ß-hydroxy-(1αH,7ßH,11ßH)-guai-8(12),8(14)-diepoxy-4-en-3-one (M-8), 10α-hydroxy-(1αH,7ßH,11αH)-guai-8(13), 8(14)-diepoxy-4-en-3-one (M-9), 10α-hydroxy-(1αH,7ßH,11ßH)-guai-8(12),8(14)-diepoxy-4-en-3-one (M-10), 10α,14,15-trihydroxy-(1αH,7ßH)-guai-4-en-3,8-dione (M-11), 10ß-hydroxy-(1αH,7ßH)-guai-4-en-3,8-dioxo-13-oic acid (M-12), (1αH,7ßH)-guai-4,10(14)-dien-3, 8-dioxo-13-oic acid (M-13), 5ß,10ß-dihydroxy-(1αH,7ßH,11αH)-guai-8(13),8(14)-diepoxide (M-14), 10ß,14-dihydroxycurcumol (M-15), and 5ß,10ß,14-trihydroxy-(1αH,7ßH)-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.

Three major metabolites of mulberroside A in rat intestinal contents and feces.

Mulberroside A, a major stilbene constituent of MORUS ALBA L. (Moraceae), displays significant antitussive and antiasthmatic effects in animals. As part of our ongoing research on its biotransformation in rats, mulberroside A was orally administered to rats, and the metabolites in the gastrointestinal contents and feces were investigated. Three major metabolites were isolated from the feces of rats and identified as oxyresveratrol-2- O- beta- D-glucopyranoside ( 1), oxyresveratrol-3'- O- beta- D-glucopyranoside ( 2), and oxyresveratrol ( 3) on the basis of chemical and spectroscopic evidence. The three metabolites were also detected in the small intestinal contents of rats following oral administration of mulberroside A. These findings suggest that mulberroside A is metabolized prior to absorption into the body.