Identification of the metabolites of episesamin in rat bile and human liver microsomes

Abstract

Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7′β,8α, 8′α)-3,4-dihydroxy-3′,4′-methylenedioxy-7,9′: 7′,9-diepoxylignane (EC-1-1), (7α,7′β,8α, 8′α)-3,4-methylenedioxy-3′,4′-dihydroxy-7,9′: 7′,9-diepoxylignane (EC-1-2) and (7α,7′β,8α, 8′α)-3,4:3′,4′-bis(dihydroxy)-7,9′:7′, 9-diepoxylignane (EC-2), (7α,7′β,8α,8′α)-3- methoxy-4-hydroxy-3′,4′-methylenedioxy-7,9′:7′, 9-diepoxylignane (EC-1m-1), (7α,7′β,8α,8′α)- 3,4-methylenedioxy-3′-methoxy-4′-hydroxy-7,9′:7′, 9-diepoxylignane (EC-1m-2), (7α,7′β,8α,8′α)- 3-methoxy-4-hydroxy-3′,4′-dihydroxy-7,9′:7′, 9-diepoxylignane (EC-2m-1) and (7α,7′β,8α, 8′α)-3,4-dihydroxy-3′-methoxy-4′-hydroxy-7,9′: 7′,9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans. © 2012 The Pharmaceutical Society of Japan.