title: Isolation and identification of phase I metabolites of resibufogenin in rats.
abstract: 1. Resibufogenin (1), a major bufadienolide of Chinese medicine Chan Su, had a wide range of pharmacological activities. In present work, the metabolism of 1 in male Sprague-Dawley rats was investigated by identifying the metabolites of resibufogenin excreted in rat bile. 2. Following an oral dose of 60 mg/kg resibufagenin, nine metabolites were isolated from bile of rats, and their structures were identified as 3-keto- resibufogenin (2), 3-epi-resibufogenin (3), 5β-hydroxy-3-epi-resibufogenin (4), 1α, 5β-dihydroxy-3-epi-resibufogenin (5), 3α, 5β, 14α, 15β-tetrahydroxyl-bufa- 20, 22-dienolide (6), 3α, 14α, 15β-trihydroxy-bufa-20, 22-dienolide (7), 3-epi- 5β-hydroxy-bufalin (8), 12α, 16β-dihydroxy-3-epi-resibufogenin (9), and 5β, 16β-dihydroxy-3-epi-resibufogenin (10), respectively, on the basis of widely spectroscopic methods including 2D-NMR technology. It is first time to describe the metabolites of 1 in vivo, and metabolites 5-7 and 9-10 are novel. 3. On the basis of these identified metabolites, a possible metabolism pathway for 1 in rats has been proposed. This is the first systematic study on the phase I metabolites of resibufogenin.
authors.affiliation: The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Z-T
authors.initials: ZT
authors.lastname: Zhu
authors.forename: S
authors.initials: S
authors.lastname: Deng
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: B-J
authors.initials: BJ
authors.lastname: Zhang
authors.forename: H-Z
authors.initials: HZ
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: X-C
authors.initials: XC
authors.lastname: Ma
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000302:isolation & purification / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D050216:Metabolic Detoxication, Phase I; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002018:Bufanolides; D002316:Cardiotonic Agents; C005734:bufogenin