SUPPRESSION OF ALCOHOL INTAKE AFTER ADMINISTRATION OF THE CHINESE HERBAL MEDICINE, NPI-028, AND ITS DERIVATIVES

The Chinese herbal medicine, NPI-028, has been used for centuries in C hina to counteract alcohol intoxication. The present study used a numb er of different experimental conditions to determine whether NPI-028 a nd its derivatives might selectively influence alcohol intake in roden ts that naturally exhibit high alcohol intakes. It was determined that intraperitoneal (IP) injections of NPI-028 (0.5, 0.75, and 1.0 g/kg) suppressed alcohol intake by up to 30% in both alcohol-preferring P an d Fawn-Hooded (FH) rats during a continuous access schedule. These inj ections did not significantly affect food or water intakes, nor did th e highest dose of NPI-028 (1 g/kg) alter blood ethanol levels after an IP injection of 2.5 g/kg of ethanol. In P rats, it was found that NPI -028 was orally active with the dose of 1.5 g/kg having a greater effe ct on ethanol intake than the 1.0 g/kg dose; once again, food and wate r intakes were not significantly altered. In FH rats maintained on a l imited access schedule (1 hr/day), alcohol intake was completely aboli shed by 1.5 g/kg of NPI-028. Chronic IP administration of NPI-028 (0.7 5 g/kg) for four consecutive days in FH rats maintained on a continuou s access schedule did not lead to any diminution of its alcohol-suppre ssant effects. Thus, NPI-028 has significant effects on alcohol intake without much effect on water and food intake, and tolerance does not readily develop to these effects. The IP administration of a partially purified extract (NPI-031) of NPI-028, obtained by countercurrent chr omatography, also dose-dependently suppressed ethanol intake in FH rat s, but the highest dose (200 mg/kg) also significantly decreased food intake. Finally, the IP administration of puerarin (NPI-31G), an isofl avone isolated from NPI-031 by countercurrent chromatography, signific antly reduced ethanol intake in FH rats without affecting food or wate r intake. Therefore, NPI-028 and one of its pure components, NPI-031G, selectively reduced ethanol intake in alcohol-preferring rats.