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.

Keywords

• cytokines
• dopamine
• imipramine
• norepinephrine
• serotonin