Alcohol absorption inhibitors from bay leaf (Laurus nobilis): structure-requirements of sesquiterpenes for the activity.
Through a bioassay-guided separation using inhibitory activity on blood ethanol elevation in oral ethanol-loaded rat, various sesquiterpenes having an alpha-methylene-gamma-butyrolactone moiety, costunolide (1), dehydrocostus lactone (2), zaluzanin D (3), reynosin (4), santamarine (5), 3alpha-acetoxyeudesma-1,4(15),11(13)-trien-12,6alpha-+ ++olide (6) and 3-oxoeudesma-1,4,11(13)-trien-12,6alpha-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 alpha-methylene-gamma-butyrolactone moiety were synthesized from 2 and the inhibitory activities of these sesquiterpenes, together with alpha-methylene-gamma-butyrolactone (12) and its related compounds (13-16), were examined. These results indicated that the gamma-butyrolactone or gamma-butyrolactol moiety having alpha-methylene or alpha-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.
Yoshikawa
M
M
Kyoto Pharmaceutical University, Japan. shoyaku@mb.kyoto-phu.ac.jp
Shimoda
H
H
Uemura
T
T
Morikawa
T
T
Kawahara
Y
Y
Matsuda
H
H
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000042:Absorption / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D019770:Lauraceae / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D005663:Furans; D007783:Lactones; D012717:Sesquiterpenes; C014096:alpha-methylene gamma-butyrolactone; D000431:Ethanol; C018674:tetrahydrofuran; C083030:dehydrocostus lactone; C002602:costunolide; D015107:4-Butyrolactone