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), (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.
Lou
Yan
Y
Department of Natural Products Chemistry, Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China.
Zhang
Hui
H
He
Hao
H
Peng
Kaifeng
K
Kang
Ning
N
Wei
Xingchuan
X
Li
Xuegai
X
Chen
Lixia
L
Yao
Xinsheng
X
Qiu
Feng
F
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D050216:Metabolic Detoxication, Phase I; D015394:Molecular Structure; D009822:Oils, Volatile; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism* / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization
D009822:Oils, Volatile; D012717:Sesquiterpenes; C022801:curcumol