Effects of Ferula gummosa Boiss. fractions on morphine dependence in mice

Activity-guided fractionation of methanol-chloroform (1:1) extract of Ferula gummosa was carried out to investigate the isolation of the active component(s) responsible for the alleviation of morphine withdrawal syndrome induced by naloxone. Dependence was induced using subcutaneous (s.c.) injections of morphine daily for three days. On day 4, morphine was injected 0.5 h before the interaperitoneal (i.p.) injections of fractions or diazepam (5 mg/kg, i.p.) as positive control. Naloxone was injected (5 mg/kg, s.c.) 2 h after the final dose of morphine. The number of episodes of jumping during 30 min after the injection of naloxone was considered as the intensity of the withdrawal syndrome. The methanol-chloroform (1:1) extract of the aerial parts of plant was prepared and partitioned between water and chloroform. The active chloroform layer was concentrated and partitioned between methanol-water (9:1) and n-hexane. Activity was observed in the hydroalcoholic layer. This layer was concentrated and partitioned further between methanol-water (3:2) and chloroform. The chloroform layer showed a dose-dependent and significant activity. For all fractions the activity was observed at 470 mg/kg. Further purification on silica gel column chromatography gave a pure compound, which was 10 times as effective as the crude extract. The results of this study indicated that the plant extract contained component(s) that could be useful for the alleviation of morphine withdrawal syndrome.