Abstract
INTRODUCTION: Oxidative stress and proinflammatory signaling in the brain have been found to have a significant role in the pathogenesis of depression. Therefore, drugs that reduce oxidative stress and neuroinflammation may be helpful in depression as monotherapy or as an adjunct to conventional antidepressants. Zileuton, a 5-lipoxygenase inhibitor, has been identified as a putative antidepressant in an in vitro study. It was shown to modulate the proinflammatory macrophage response in the brain and, hence, neuroinflammation. Currently, there are no antidepressants that target the inflammatory component of depression. Hence, this would be a desirable addition to our armamentarium against depression, particularly in patients with poor responses to antidepressants. Phyllanthus emblica, commonly known as amla, is an important medicinal plant from the traditional Indian system of medicine. It has significant antioxidant and anti-inflammatory activity and is believed to be neuroprotective. However, its role as an antidepressant needs further elucidation. METHODS: The primary aim of this study was to evaluate whether zileuton and aqueous extract of Phyllanthus emblica exert antidepressant activity in a chronic stress model of depression in Swiss albino mice. A total of six groups (six mice each) were used in the study. They were disease control (given normal saline), positive control (PC; given fluoxetine), Phyllanthus emblica low dose and high dose, and zileuton low and high dose. After induction of depression, drugs were given for 14 days. The antidepressant effect of the study drugs was evaluated using two behavioral tests: the tail suspension test (TST) and the forced swim test (FST). Interleukin-6 (IL-6) levels in the hippocampus were measured on day 45. Descriptive statistics and ANOVA were used for the statistical analysis. P-value < 0.05 was considered statistically significant. RESULTS: It was observed that zileuton and aqueous extract of Phyllanthus emblica decreased the duration of immobility in both behavioral tests, which indicated their antidepressant effect. Also, it was observed that the antidepressant effect of zileuton and Phyllanthus emblica was comparable to fluoxetine. There was a statistically significant decrease (p < 0.001) in hippocampal IL-6 levels in the positive control (fluoxetine) group, Phyllanthus emblica low dose and high dose groups, and zileuton low dose and high dose groups compared to the disease control group. CONCLUSION: According to our study's findings, zileuton and Phyllanthus emblica exert an antidepressant effect comparable to that of fluoxetine, as evidenced by the reduction in immobility time in the behavioral tests. The reduction in the IL-6 levels by zileuton and Phyllanthus emblica signifies a decrease in neuroinflammation, which may be responsible for the antidepressant effect.