NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway contribute to the antidepressant-like effect of Yueju pill in mice

Abstract

The present study aims to evaluate the involvement of N-methyl-d-aspartate receptor and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in antidepressant-like effects of Yueju pill (YJ), a Chinese herbal medicine. The immobility time in tail suspension test (TST) and forced swim test (FST) was used to assess the antidepressant effects. Prior administration of L-arginine (750 mg/kg, intraperitoneal [i.p.]), a NO synthase substrate that enhances NO signaling or sildenafil (5 mg/kg, i.p.), a phosphodiesterase 5 inhibitor that enhances cGMP, blunted the antidepressant-like activity of YJ (2.7 g/kg, i.g.). Co-treatment of ineffective dose of YJ (1.35 g/kg, i.g.) with one of the reagents that suppress the NO/cGMP signaling, including methylene blue (10 mg/kg, i.p.), an inhibitor of NO synthase; 7-NI (7-nitroinidazole, 30 mg/kg, i.p.), an nNOS specific inhibitor; L-NAME (10 mg/kg, i.p.), a non-specific inhibitor of NO synthase; and MK-801 (0.05 mg/kg, i.p.), an NMDA receptor antagonist, reduced the immobility time in TST and FST, compared with those in vehicle or single drug treatment groups. Neither above drugs alone or co-administrated with YJ affected locomotor activity or anxiety behavior in open field test. Thus, our results suggest that the antidepressant-like action of YJ may depend on the inhibition of NMDA/NO/cGMP pathway.

Review of Herbal Medicines for the Treatment of Depression

“…110 In the mice behavior test using the tail suspension and forced swimming tests, Yueju pill was used to examine its antidepressant effect, which may mediate the inhibition of NMDA receptors and the NO/cGMP pathway. 111 Plantago asiatica, Scrophularia ningpoensis, and Ilex pubescens also reportedly exert antidepressant effects in the LH model. 112 In general, animal models can partially simulate the state of depression, but they cannot fully reproduce patients' suicidal behavior and difficult-to-observe symptoms such as mood swings.…”

“…110 In the mice behavior test using the tail suspension and forced swimming tests, Yueju pill was used to examine its antidepressant effect, which may mediate the inhibition of NMDA receptors and the NO/cGMP pathway. 111 Plantago asiatica , Scrophularia ningpoensis , and Ilex pubescens also reportedly exert antidepressant effects in the LH model. 112…”

Antidepressant-like effect of acute dose of Naringin involves suppression of NR1 and activation of protein kinase A/cyclic adenosine monophosphate response element-binding protein/brain-derived neurotrophic factor signaling in hippocampus

“…injection. The doses of ketamine (30 mg/kg), NMDA (750 mg/kg,) and MK-801(0.05 mg/kg,) were referred to the published literature (Xue et al, 2013;Wang et al, 2019;Zhang et al, 2020;Khan et al, 2021).…”

Early Enhancement of Neuroplasticity Index, the Ratio of Serum Brain-Derived Neurotrophic Factor Level to HAMD-24 Score, in Predicting the Long-Term Antidepressant Efficacy

“…Traditional medicine has been used as an alternative monotherapy or an adjunct to conventional antidepressant therapy, whose efficacy and safety has been supported on the basis of increasing number of clinical trials ( Zhang et al, 2007 ; Qin et al, 2011 ; Wang et al, 2012 ; Yang et al, 2020 ). Yueju pill is a multiherbal pill formulated 800 years ago to treat syndromes associated with mood disorders ( Ren and Chen, 2017 ; Wang et al, 2019 ). It contains multiple antidepressant components and some of the bioactive compounds have been identified ( Wei et al, 2008 ; Zhang et al, 2015 ; Wu et al, 2016 ).…”