Five new eudesmane-type sesquiterpenoid lactones biotransformed from atractylenolide I by rat hepatic microsomes

The work presented here is the first study performed on the biotransformation and/or metabolism of atractylenolide I (1) as a valuable anti-inflammatory and chemopreventive agent, using liver microsomes from rats pre-treated with sodium phenobarbital. Two known eudesmane-type sesquiterpenoid lactones, namely 1 beta-acetoxyatractylenolide 1 (2) and 1 beta-hydroxy-atractylenolide 1(3), and five new ones, namely 3 beta-hydroxy-atractylenolide 1(4), 1 beta,13-dihydroxy-atractylenolide I (5),1 beta,2 alpha-dihydroxy-atractylenolide I (6), 1 beta,3 alpha-dihydroxy-atractylenolide 1(7), and 1 beta,3 beta-dihydroxy-atractylenolide I (8) were obtained. Their chemical structures were unambiguously established by both 1D and 2D NMR as well as mass spectroscopic techniques. The result indicated that the parent prototype compound 1 could be specifically oxidized at C-1, C-2 and C-3 of A-ring, suggesting that the oxidizable of I may contribute to its in vivo anti-inflammatory and chemopreventive effects. And the result also provided valuable information for further investigation of relationship among metabolic activation and liver microsomal cytochrome P450 enzyme isoforms. (C) 2013 Elsevier B.V. All rights reserved.