Alcohol absorption inhibitors from bay leaf (Laurus nobilis): structure-requirements of sesquiterpenes for the activity Original Research Article

Through a bioassay-guided separation using inhibitory activity on blood ethanol elevation in oral ethanol-loaded rat, various sesquiterpenes having an α-methylene-γ-butyrolactone moiety, costunolide (1), dehydrocostus lactone (2), zaluzanin D (3), reynosin (4), santamarine (5), 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide (6) and 3-oxoeudesma-1,4,11(13)-trien-12,6α-olide (7), were isolated as the active principle from the leaves of Laurus nobilis (bay leaf, laurel). In order to characterize the structure requirement for the activity, several reduction products (2a–2d) and amino acid adducts (2e, 2f) of the α-methylene-γ-butyrolactone moiety were synthesized from 2 and the inhibitory activities of these sesquiterpenes, together with α-methylene-γ-butyrolactone (12) and its related compounds (13–16), were examined. These results indicated that the γ-butyrolactone or γ-butyrolactol moiety having α-methylene or α-methyl group was essential for the inhibitory activity on ethanol absorption. Since 1, 2 and 12 showed no significant effect on glucose absorption, these sesquiterpenes appeared to selectively inhibit ethanol absorption. In addition, the acute toxicities of 1 and 2 in a single oral administration were found to be lower than that of 12.