Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata Linneaus in mice

Abstract

A benzoflavone moiety (BZF) has recently been reported to be liable for many of the biological effects of the plant Passiflora incarnata Linneaus. In light of various reports mentioning the usefulness of P. incarnata in tobacco addiction, studies have been performed using four doses (1, 5, 10 and 20 mg/kg) of the bioactive BZF moiety isolated from the aerial parts of P. incarnata. In a 7-day experimental regimen, mice (n = 5) were given nicotine hydrogen tartrate (2 mg/kg), and combinations of nicotine with four doses of BZF (NnP-1, NnP-5, NnP-10 and NnP-20) q.i.d. by the s.c. route. At the end of the 7 days of treatment, naloxone was given to the mice from all groups to induce a nicotine withdrawal syndrome. The mice that had been treated with 10 and 20 mg/kg dose of BZF concurrently with nicotine showed a significantly fewer number of withdrawal jumps relative to the group treated with nicotine alone (Nn group). Separately, in a 14-day treatment regimen, mice (n = 10; for the N group, n = 12) were administered nicotine (2 mg/kg) and combinations of nicotine with four doses of BZF (NP-1, NP-5, NP-10, NP-20 groups) q.i.d. by the s.c. route. Spontaneous physical and behavioural signs of nicotine dependence were observed 3 hours after cessation of treatments on the 14th day. Mice administered with combinations of nicotine and 5, 10 and 20 mg/kg doses of BZF (i.e. NP-5, NP10 and NP-20 groups), exhibited less intensity and severity of withdrawal effects compared to the mice treated with nicotine alone. Those mice treated with the two highest doses of BZF,in combination with nicotine (NP-10 and NP-20), showed significantly fewer nicotine-abstinence withdrawal jumps and normal ambulatory behaviour. BZF treatment prevented weight loss and resulted in normal performance in the swimming endurance test, which may be a measure of stress and/or depression. Similarly, acute administration of a single 20 mg/kg dose of BZF prevented some of the nicotine-withdrawal effects; lower doses were almost inert. These studies, although preliminary, suggest that the BZF may have value in treating nicotine addiction.