Antidepressant- and anxiolytic-like actions of Cajanus cajan seed extract mediated through monoaminergic, nitric oxide-cyclic GMP and GABAergic pathways

Abstract

Ethnopharmacological relevance: The seeds of Cajanus cajan (L) Millsp, are used in Traditional medicine for the treatment of anxiety and other neurological disorders. Hence, this study is designed to investigate the antidepressant- and anxiolytic-like properties of ethanol seed extract of Cajanus cajan (CC) in mice.

Materials and methods: CC (50, 100 or 200 mg/kg, p.o.) was administered 1h before subjecting the animals to different behavioral models: forced swim test (FST) and tail suspension test (TST) (depressive-like behaviour), open field test (OFT), elevated plus maze (EPM), light-dark test (LDT) and hole-board test (HBT) for anxiety-like behaviour. To ascertain the pharmacodynamic of CC mice were pretreated with monoaminergic, nitrergic and GABAergic receptors antagonists. As well as molecular docking analysis of about 19 flavonoids present in CC on GABA_A, α₂ adrenoceptors and 5-HT_2A receptors.

Results: CC (50, 100 or 200 mg/kg, p.o.) treatment significantly reduced immobile time in both FST and TST when compared with vehicle-treated control. However, the pretreatment of mice with prazosin/yohimbine (α_1/2 adrenoceptor antagonists, respectively), WAY100635 (5-HT_1A receptor antagonist), ketanserin (5-HT_2A receptor antagonist), sulpiride (dopamine D₂ receptor antagonist), L-N^G-Nitro arginine methyl ester (L-NAME), or methylene blue reversed the antidepressant-like effect of CC. In anxiety model, CC produced significant (p < 0.05) increase in open arms exploration and head dipping behavior which was reversed by flumazenil (benzodiazepine receptor antagonist) in the EPM. Docking analysis showed significant binding affinity of orientin, vitexin, pinostrobin and quercetin with 5HT_2A, α₂-adrenoceptor and GABA_A receptors.

Conclusion: Findings from this study showed that C.cajan seeds extract exerts antidepressant-like effect through participation of monoaminergic systems (5-HT₂ receptor, α₁/α₂-adrenoceptors, and dopamine D₂-receptors), nitric oxide-cyclic GMP pathway and anxiolytic-like effect via GABA_A benzodiazepine receptors. Moreso, presence of flavonoids with significant binding energies with monoaminergic and GABAergic systems support the potential of the extract in the management of mixed anxiety-depressive illness.

Keywords: Anxiety; Cajanus cajan; Elevated plus maze; Flavonoids; Forced swim test; depression.