Background: Previous work found that extracts from the roots of Salvia miltiorrhiza, a Chinese medicinal herb, reduced alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to evaluate whether miltirone, one of the possible active constituents of Salvia miltiorrhiza, might be responsible for the reducing effect of the extracts on alcohol intake. Methods: An initial experiment assessed the effect of 100 mg/kg (i.g.) of four extracts of Salvia miltiorrhiza, differing in miltirone content (0%, 2%, 3% and 7%, respectively), on alcohol intake in alcohol-experienced sP rats exposed to the 2-bottle "alcohol (10%, v/v) vs water" choice regimen. Subsequently, the effect of pure miltirone (2.5-10 mg/kg, i.g., i.e. a dose-range comparable to its content in the effective doses of the active extracts) on acquisition and maintenance of alcohol drinking behavior was evaluated in alcohol-naive and -experienced sP rats exposed to the 2-bottle choice regimen. The effect of miltirone (10 mg/kg, i.g.) on blood alcohol levels was assessed after the i.g. and i.p. administration of alcohol. Finally, the effect of miltirone (30-100 mg/kg, i.g.) on the severity of alcohol withdrawal syndrome was evaluated in Wistar rats made physically dependent on alcohol by the repeated administration of intoxicating doses of alcohol. Results: The reducing effect of four different extracts of Salvia miltiorrhiza on alcohol intake was positively and significantly correlated with their miltirone content. Pure miltirone reduced alcohol intake in alcohol-experienced rats and delayed acquisition of alcohol drinking behavior in alcohol-naive rats. Similarly to Salvia miltiorrhiza extracts, miltirone markedly reduced blood alcohol levels when alcohol was administered i.g. but not i.p., suggesting that miltirone hampered alcohol absorption from the gastrointestinal system. Finally, miltirone failed to affect the severity of alcohol withdrawal syndrome in alcohol-dependent rats. Conclusions: The results of the present study suggest that miltirone is the likely active constituent of Salvia miltiorrhiza responsible for the reducing effect of its extracts on alcohol intake in different experimental models of excessive alcohol consumption.
Identification of miltirone as active ingredient of Salvia miltiorrhiza responsible for the reducing effect of root extracts on alcohol intake in rats
Colombo G;Gessa GL;
2006
Abstract
Background: Previous work found that extracts from the roots of Salvia miltiorrhiza, a Chinese medicinal herb, reduced alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to evaluate whether miltirone, one of the possible active constituents of Salvia miltiorrhiza, might be responsible for the reducing effect of the extracts on alcohol intake. Methods: An initial experiment assessed the effect of 100 mg/kg (i.g.) of four extracts of Salvia miltiorrhiza, differing in miltirone content (0%, 2%, 3% and 7%, respectively), on alcohol intake in alcohol-experienced sP rats exposed to the 2-bottle "alcohol (10%, v/v) vs water" choice regimen. Subsequently, the effect of pure miltirone (2.5-10 mg/kg, i.g., i.e. a dose-range comparable to its content in the effective doses of the active extracts) on acquisition and maintenance of alcohol drinking behavior was evaluated in alcohol-naive and -experienced sP rats exposed to the 2-bottle choice regimen. The effect of miltirone (10 mg/kg, i.g.) on blood alcohol levels was assessed after the i.g. and i.p. administration of alcohol. Finally, the effect of miltirone (30-100 mg/kg, i.g.) on the severity of alcohol withdrawal syndrome was evaluated in Wistar rats made physically dependent on alcohol by the repeated administration of intoxicating doses of alcohol. Results: The reducing effect of four different extracts of Salvia miltiorrhiza on alcohol intake was positively and significantly correlated with their miltirone content. Pure miltirone reduced alcohol intake in alcohol-experienced rats and delayed acquisition of alcohol drinking behavior in alcohol-naive rats. Similarly to Salvia miltiorrhiza extracts, miltirone markedly reduced blood alcohol levels when alcohol was administered i.g. but not i.p., suggesting that miltirone hampered alcohol absorption from the gastrointestinal system. Finally, miltirone failed to affect the severity of alcohol withdrawal syndrome in alcohol-dependent rats. Conclusions: The results of the present study suggest that miltirone is the likely active constituent of Salvia miltiorrhiza responsible for the reducing effect of its extracts on alcohol intake in different experimental models of excessive alcohol consumption.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
