Involvement of l‐arginine‐nitric oxide pathway in the antidepressant and memory promoting effects of morin in mice

Abstract

l‐Arginine‐nitric oxide pathway has been reported to be involved in the mediation of the psychopharmacological effects of many psychotropic drugs. Previous studies have shown that morin, a psychotropic compound isolated from mulberry leaf produces functional psychopharmacological effects indicative of antidepressant, antipsychotic, anxiolytic and nootropic properties. However, the role of l‐arginine‐nitric oxide pathway in the psychotropic effects of morin has not been fully investigated, hence, the need for this study. Male Swiss mice were pretreated individually or in combination with nitric oxide precursor [l‐arginine (750 mg/kg, i.p.)], competitive nonselective nitric oxide synthase (NOS) inhibitor [N(G)‐nitro‐l‐arginine methyl ester (l‐NAME, i.p) (50 mg/kg)] or selective neuronal NOS inhibitor [methylene blue (3.75 mg/kg, i.p)] prior to morin (100 mg/kg, i.p.) or saline (10 mL/kg, i.p.) treatment. Psychopharmacological activities were then evaluated 30 min later using open field, Y‐maze, and forced swim tests. l‐Arginine significantly reversed the effects of morin on locomotion, memory and depression in mice. The reduced motor activity and enhanced memory function produced by morin were significantly attenuated by methylene blue but augmented the antimobility activity of morin in the FST. Moreover, l‐NAME potentiated the psychopharmacological effects of morin in the open field and forced swim tests but reduced its memory promoting effect. Meanwhile, morin supplementation reversed the effects of l‐arginine on l‐NAME‐treated mice in all behavioral models. The results of this study suggest that l‐arginine‐nitric oxide pathway might play a role in the modulation of the antidepressant and memory promoting effects of morin in mice.

Probable mechanisms involved in the antiepileptic activity of Clerodendrum polycephalum Baker (Labiatae) leaf extract in mice exposed to chemical‐induced seizures

“…However, animals pretreated with flumazenil before CP (100 mg/kg) or DZP inhibited their anticonvulsant activity (Table 2). In another experiment, the modulatory role of the nitric oxide‐cGMP pathway on CP‐induced anticonvulsant activity was examined (Ben‐Azu, Aderibigbe, Ajayi, Umukoro, & Iwalewa, 2019). While L‐arginine alone prolonged the duration of PTZ‐induced seizures (Table 2), the administration of L‐arginine before CP (100 mg/kg) significantly reduced the seizure threshold in comparison with CP‐only treatment (Table 2).…”

L‐arginine metabolism ameliorates age‐related cognitive impairment by Amuc_1100‐mediated gut homeostasis maintaining

“…L‐arginine was metabolized into many bioactive molecules in a tightly regulated manner in mammals (Morris, 2007 ). L‐arginine produced NO through nitric oxide synthase (Nos) (Paul & Ekambaram, 2011 ), including endothelial Nos (eNos), neuronal Nos (nNos), and inducible Nos (iNos) (Ben‐Azu et al., 2019 ; Zhang et al., 2013 ). eNos loss contributed to APP amyloid formation processes and cognitive decline (Bergin et al., 2018 ), nNos played a vital role in synaptic plasticity and learning and memory (Paul & Ekambaram, 2011 ), while iNos could act as proinflammatory agents (Haj‐Mirzaian et al., 2016 ).…”

“…eNos loss contributed to APP amyloid formation processes and cognitive decline (Bergin et al., 2018 ), nNos played a vital role in synaptic plasticity and learning and memory (Paul & Ekambaram, 2011 ), while iNos could act as proinflammatory agents (Haj‐Mirzaian et al., 2016 ). NO was also involved in synaptic plasticity, long‐term potentiation, and memory consolidation (Ben‐Azu et al., 2019 ). NO deficiency promoted endothelial dysfunction, accelerated amyloid formation and accumulation, reduced synaptic plasticity, activated microglia, and induces neuroinflammation (Katusic & Austin, 2014 ).…”

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

“…The results also indicated its possible role in inflammasome activation, as morin reduced levels of the inflammasome pathway markers TNF-α, IL-1β, toll-like receptor-4 (TLR-4), NLRP3, and caspase-1, indicating its promising potential in alleviating the inflammatory basis of the disease [ 264 ]. Another study performed on mice suggested that the antidepressant effects of morin could be mediated through the L-arginine-NO pathway, as beneficial effects of morin on despair-like behavior were reversed by the NO precursor L-arginine [ 265 ].…”