BIOORGANIC & MEDICINAL CHEMISTRY ~RS Bioorganic & Medicinal Chemistry Letters 9 (1999) 2647-2652 Pergamon PREVENTIVE EFFECT OF SESQUITERPENES FROM BAY LEAF ON BLOOD ETHANOL ELEVATION IN ETHANOL-LOADED RAT: STRUCTURE REQUIREMENT AND SUPPRESSION OF GASTRIC EMPTYING Hisashi Matsuda, Hiroshi Shimoda, Toshiaki Uemura and Masayuki Yoshikawa* Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Received 24 June 1999; accepted 3 August 1999 Abstract: The methanolic extract from the leaves of Laurus nobilis (bay leaf, laurel) potently inhibited the elevation of blood ethanol level in ethanol-loaded rat. Through bioassay-guided separation, costunolide, dehydrocostus lactone, and santamarine were isolated as the active constituents and the ct-methylene-7- butyrolactone structure was found to be essential/'or the preventive effect on ethanol absorption. In addition, the retardation of gastric emptying seemed to be partially involved in the preventive effects. © 1999 Elsevier Science Ltd. All rights reserved. Long-term consumption of alcohol in large quantities induces a number of disorders in addition to hematopathy, gastrointestinal disorder, chronic pancreatitis, peripheral nerve disorder, myocardosis, hypertentonia and hematopoiesis. Not only organ disorders but also mental disorders in alcoholism have serious social effects, and many patients with alcoholic disorders is increasing in many countries. Cyanamide and disulfilam, aldehyde dehydrogenase inhibitors, are used clinically for the treatment of chronic alcoholism. However, it is known that dehydrogenase inhibitors force alcoholics to quit drinking based on the fear of unpleasant reaction elicited after ethanol intake, but these medicine are also reported to show many strong side effects. Recently, we found many active saponins from natural medicines that prevent increases in blood alcohol levels: 1 for example, elatosides 2 from the bark of Aralia clara, sapindosides ~ from the pericarps of Sapindus mukurossi, escins 3 from the seeds of Aesculus hippocastanum, camelliasaponins 4 from the seeds of Camellia japonica, senegins and senegasaponins 5 from the root of Polygala senega var. latifolia, and momordins 6 from the fruit of Kochia scoparia. Furthermore, we have characterized new dihydroflavonols with inhibitory effect on alcohol-induced muscular relaxation and hepatoprotective activity from the fruit of Hovenia dulcis, which has been used for treatment of alcohol intoxication in Chinese traditional medicine. 7 In our continuing search for inhibitors of blood alcohol elevation from natural resources, we found a potent preventive activity in the methanolic extract of the leaves of Lauraceae plant Laurus nobilis (bay leaf, laurel). L. nobilis is widely cultivated in Mediterranean and the leaves are used as a herb in cooking for soup or stew. The leaves of L. nobilis are also used as a herbal medicine for excitant, stomachic, and digestin in Europe. As the pharmacological properties of L. nobilis, it has been reported to have antiulcer (seed) 8 and antidiabetic (leaf) 9 effects, and to enhance in liver glutathione S-transferase (GST) activity ~°, Here, we found that the methanolic extract from the leaves of L. nobilb has a preventive effect on increases in blood ethanol level. In this paper, we describe the characterization of the active sesquiterpenes from the leaves of L. nobilis, the structure-requirement for the activity, and the action property. 0960-894X/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII: S0960-894X(99)00442-4