Mitragynine Reverses LPS-Induced Anxiety and Oxidative Stress in Rats via Modulation of Toll-Like Receptor 4 and Malondialdehyde (MDA)

Neuroinflammation marked by increased toll-like receptor 4 (TLR4) 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. This study investigated the effects of mitragynine on anxiety-like behaviours, TLR4 expression and oxidative stress in the brains of rats treated with lipopolysaccharide (LPS). Rats received a single 1 mg/kg LPS injection intraperitoneally (i.p.) to induce anxiety. Mitragynine was then administered at doses of 1 mg/kg, 5 mg/kg or 10 mg/kg body weight 1 hour post-LPS administration. The impact of mitragynine on anxiety was assessed using the elevated plus maze (EPM). TLR4 expression was measured using a Western blot, while oxidative stress markers (MDA, GSH, GPx, CAT) were measured using protein assays. Mitragynine ameliorated LPS-induced anxiety behaviours in the EPM. Mitragynine (5 mg/kg 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. As conclusion, the Mitragynine effects on LPS-induced anxiety may be associated with the reduction in TLR4 expression and MDA level.