Isolation and identification of metabolites of osthole in rats.
Osthole (Ost), one of the major components of Cnidium monnieri (L.) Cusson, is had the structure of an isopentenoxy-coumarin with a range of pharmacological activities. In the present study, the metabolism of Ost in male Sprague-Dawley rats was investigated by identifying Ost metabolites excreted in rat urine.        Following an oral dose of 40 mg/kg Ost, 10 phase I and 3 phase II metabolites were isolated from the urine of rats, and their structures identified on the basis of a range of spectroscopic data, including 2D-NMR techniques. These metabolites were fully characterized as 5'-hydroxyl-osthole (M-1), osthenol (M-2), 4'-hydroxyl-osthole (M-3), 3, 5'-dihydroxyl-osthole (M-4), 5'-hydroxyl-osthenol (M-5), 4'-hydroxyl-2', 3'-dihydro-osthenol (M-6), 4'-hydroxyl-osthenol (M-7), 3, 4'-dihydroxyl-osthole (M-8), 2', 3'-dihydroxyl-osthole (M-9), 5'-hydroxyl-2', 3'-dihydroosthole (M-10), osthenol-7-O-β-D-glucuronide (M-11), osthole-4'-O-β-D-glucuronide (M-12) and osthole-5'-O-β-D-glycuronate (M-13). This is the first identification of M-1, M-3 to M-13 in vivo.        On the basis of the metabolites profile, a possible metabolic pathway for Ost metabolism in rats has been proposed. This is the first systematic study on the phases I and II metabolites of 8-isopentenoxy-coumarin derivative.
School of Pharmacy, Pharmacokinetic and Drug Transport Key Laboratory, Dalian Medical University, Dalian, China.
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Wang
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Zhang
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Deng
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Tian
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Liu
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D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D031048:Cnidium / Q000737:chemistry*; D003374:Coumarins / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D000276:Adjuvants, Immunologic; D003374:Coumarins; C046627:osthol