Mitigation of Lps-induced Anxiety and Oxidative Stress Through Mitragynine: Targeting Tlr-4 and Mda Modulation

Abstract

Introduction: Neuroinflammation marked by increased toll-like receptor (TLR)-4 expression contributes to the pathogenesis of anxiety disorders. Mitragynine, an indole alkaloid derived from the kratom plant (Mitragyna speciosa Korth), shows promise as a potential pharmacotherapeutic agent for anxiety due to its anti-inflammatory activity. However, the mechanism involved in its anxiolytic effect remains unclear. Aims: This study investigated the effects of mitragynine on anxiety-like behaviours, TLR4 expression and oxidative stress in the frontal cortex of rats treated with lipopolysaccharide (LPS). Methodology: Rats received a single 1 mg/kg LPS injection intraperitoneally (i.p.) to induce anxiety. Mitragynine was then administered at the doses of 1, 5 or 10 mg/kg body weight 1h post-LPS administration. Impact of mitragynine on anxiety was assessed using both open field test (OFT) and elevated plus maze (EPM). TLR4 expression was measured using western blot, while oxidative stress markers (MDA, GSH, GPx, CAT) were measured using protein assays. Results: Mitragynine ameliorated LPS-induced anxiety behaviours in the EPM. Mitragynine (5 and 10 mg/kg) reversed the effect of LPS on TLR4 expression in the rats’ brains. All doses of mitragynine reduced lipid peroxidation in the frontal cortex of LPS-treated rats. Conclusion: Mitragyninemitigates LPS-induced anxiety by alleviating lipid peroxidation in the frontal cortex.