Involvement of GABAergic and nitrergic systems in the anxiolytic and hypnotic effects of Curcuma longa: its interaction with anxiolytic-hypnotics.

Abstract

Concurrent use of herbs with drugs have become a major healthcare problem. Herb-drug interactions could lead to therapeutic failure or toxicity. Hence, this study seeks to evaluate the impact of combining Curcuma longa rhizome (CL) with selected anxiolytic and hypnotic drugs. CL (100, 200 or 400mg/kg, p.o.) was administered to mice 1h before subjecting the animals to elevated plus maze (EPM), hole board test (HBT), open field test (OFT) and rotarod test for anxiolytic-like effect as well as hexobarbitone-induced sleeping time (HIST) for hypnotic activity. The involvement of GABAergic and nitrergic systems in CL-induced anxiolytic and hypnotic actions were also evaluated. The effect of concurrent use of CL with midazolam, imipramine, nifedipine, propranolol and carbamazepine were evaluated in anxiolytic-hypnosis models. The peak anxiolytic-like effect of CL was obtained at 400mg/kg in the EPM and hole-board test without affecting muscle coordination in the rotarod test while the peak hypnosis-potentiation was observed at 100mg/kg. CL-induced anxiolytic-hypnotic-like effects were reversed by the pretreatment of mice with flumazenil or NG-nitro-l-arginine. Curcuma longa possesses anxiolytic and hypnotic effects through its interaction with GABAergic and nitrergic systems. Conversely, co-administration of C.longa with midazolam potentiate barbiturate-induced hypnosis.