Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus

Abstract

Context: Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Zanthoxylum alatum Roxb. (Rutaceae), commonly called Timur, has high medicinal value and is used ethnomedicinally for the treatment of various diseases.Objective: To evaluate the effect of hexane extract of Z. alatum seeds (ZAHE) on lipopolysaccharide (LPS)-induced depression-like behaviour in Swiss albino mice.Materials and methods: Mice were treated with ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) for 14 days. On 14th day of the treatment, depression-like behaviour was induced by LPS (0.83 mg/kg injected i.p.) and after 24 h of LPS administration, it was assessed by measuring behavioural parameters and biochemical estimations.Results: Behavioural tests, including the open field test, forced swimming test, tail suspension test and sucrose preference test revealed that ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) alleviated the depression symptoms of LPS-induced mice. Moreover, ZAHE treatments reversed the LPS-induced alterations in the concentrations of norepinephrine and serotonin (5-HT) and inhibited the expression of brain-derived neurotrophic factor, pro-inflammatory cytokines and oxido-nitrosative stress in the mice. Acute toxicity was calculated to be LD50 > 2500 mg/kg.Discussion and conclusions: This study showed that LPS-induced depression in mice was significantly prevented by ZAHE at both the dosages. In conclusion, ZAHE exhibited an antidepressant activity by altering monoaminergic neurotransmitters in the brain combined with its anti-inflammatory potential. Thus, it could be an effective therapeutic against inflammation-induced depression and other brain disorders.

Suppression of behavioral activity and hippocampal noradrenaline caused by surgical stress in type 2 diabetes model mice

“…In the hippocampus, a decrease of NA is associated with mental impairments such as a decrease of activity, depression and cognitive dysfunction [18][19][20]33]. In the present study, hippocampal NA level was decreased 24 hours after surgical stress.…”

Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway

“…Moreover, the present results are in line with those of previous studies using CMS mice ( 17 , 31 , 32 ). It has been shown that abnormal levels of monoamine neurotransmitters are a typical feature of depression and stress in animals, and have been proposed as the principal pathogenic factor involved in this condition ( 10 ). The present results indicated that the levels of neurotransmitters, 5-HT and NE, decreased significantly after CMS exposure, which is consistent with previous studies ( 3 , 32 ).…”

“…Moreover, inflammatory cytokines impair neurogenesis, activity of neurotrophic factors and neuronal plasticity ( 8 , 9 ). Inflammatory cytokines have been proposed to regulate monoamine neurotransmitter metabolism by inhibiting neurotransmitter synthesis and promoting monoamine neurotransmitter hydrolysis ( 10 , 11 ). Therefore, inhibiting inflammation may be a potential therapeutic strategy for depression ( 12 , 13 ).…”

A review on effective utilization, phytochemical compounds, pharmacological intervention of a popularly used plant for developing a new drug: Zanthoxylum armatum with reference to its anticancer activity

“…The behavioural as well as biochemical and molecular studies have shown that the seed of the plant possesses significant antidepressant property. 31…”