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Alcohol and Alcoholism Vol. 37, No. 2, pp. 121-127, 2002
© 2002 Medical Council on Alcohol

INHIBITORY MECHANISM OF COSTUNOLIDE, A SESQUITERPENE LACTONE ISOLATED FROM LAURUS NOBILIS, ON BLOOD-ETHANOL ELEVATION IN RATS: INVOLVEMENT OF INHIBITION OF GASTRIC EMPTYING AND INCREASE IN GASTRIC JUICE SECRETION

Hisashi Matsuda, Hiroshi Shimoda, Kiyofumi Ninomiya and Masayuki Yoshikawa,*

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Received 22 May 2001; first review notified 17 July 2001; accepted 30 July 2001

Basic inhibitory mechanisms of costunolide and its active component, {alpha}-methylene-{gamma}-butyrolactone ({alpha}-MGBL), on blood-ethanol elevation were investigated in rats. In normal rats, blood-ethanol elevation (30 min later) induced by 20% (v/v) ethanol [5 ml/kg, per os (p.o.)] was strongly inhibited by pretreatment (30 min earlier) with costunolide and {alpha}-MGBL (50 mg/kg, p.o.). In pylorus-ligated rats given ethanol, blood-ethanol level (30 min) was barely elevated compared with that of normal rats. Neither costunolide nor {alpha}-MGBL affected the blood-ethanol elevation in pylorus-ligated rats or that induced by intraperitoneal and intraduodenal ethanol administration. Moreover, these compounds given orally induced no irreversible changes in alcohol dehydrogenase activity in rat liver. We continuously investigated the rate of gastric emptying in rats given various test meals. Costunolide and {alpha}-MGBL suppressed gastric emptying in rats given 20% ethanol and 1% sodium carboxymethyl cellulose. {alpha}-MGBL (50 mg/kg), but not costunolide, suppressed gastric emptying in 20% glucose-loaded rats. In an in vitro experiment, {alpha}-MGBL contracted the pylorus strip at a high concentration (20 mM), which was the estimated concentration in the stomach when the substance was given orally in vivo. These findings suggested that {alpha}-MGBL constricted the pylorus and caused delay of gastric emptying. Moreover, both compounds increased gastric fluid secretion with pepsin and mucus. In conclusion, the inhibitory effects of costunolide and {alpha}-MGBL on blood-ethanol elevation were based on inhibition of gastric emptying and dilution of the ethanol concentration by the increased gastric fluid.


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