Asiatic acid potentiates the activity of common antidepressant drugs in mice

Abstract

Rationale: Conventional pharmacotherapy for depression faces numerous challenges, including side effects. Moreover, less than 50–70% of patients fully respond to treatment, and 20–30% experience recurrence. This has led to a growing interest in alternative treatments, particularly phytotherapy. Among various plant-based compounds, asiatic acid has gained attention due to its multidirectional therapeutic properties. Objective: The aim of this study was to evaluate whether asiatic acid could enhance the antidepressant effects of conventional drugs (imipramine, reboxetine, and escitalopram). Methods: The antidepressant-like effect was tested by the forced swim test and in the tail suspension test in male Albino Swiss mice. Additionally, pharmacokinetic studies and biochemical analyses were carried out. Results: According to obtained results, asiatic acid at a sub-active dose (5 mg/kg) significantly potentiates the antidepressant activity of imipramine (15 mg/kg), reboxetine (2.5 mg/kg), and escitalopram (2 mg/kg). It was demonstrated that asiatic acid (5 mg/kg) did not increase serum or brain levels of the tested antidepressants. However, when given concurrently with escitalopram (2 mg/kg) it elevated concentrations of catalase and glutathione peroxidase as well as decreased levels of TBARS in mice brains. Co-administration of asiatic acid with imipramine (15 mg/kg) and reboxetine (2.5 mg/kg) reduced concentrations of TBARS in the tested tissue. Conclusions: Our findings give a new light on the potential use of asiatic acid in the management of depression. The terpenoid has antidepressant properties, potentially making it a valuable addition/adjunct to conventional treatment.