Mitragynine Reverses LPS-Induced Anxiety and Oxidative Stress in Rats via Modulation of Toll-Like Receptor 4 and Malondialdehyde (MDA).
- 1Centre for Drug Research, Universiti Sains Malaysia, 11800 USM Pulau Pinang, Malaysia.
- 2Department of Pharmacology, Sa'adu Zungur University, Bauchi, PMB 65 Itas/Gadau, Bauchi State, Nigeria.
Abstract
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.
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BibTeX
@article{faiz2026mitragynine,
title = {{Mitragynine Reverses LPS-Induced Anxiety and Oxidative Stress in Rats via Modulation of Toll-Like Receptor 4 and Malondialdehyde (MDA).}},
author = {Hanisah Muhammad Faiz and Suleiman Yunusa and Muhammad Hazim Abdullah and Zurina Hassan},
journal = {Tropical life sciences research},
year = {2026},
month = oct,
doi = {10.21315/tlsr2026.37.3.8},
url = {https://europepmc.org/article/MED/42997699},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mitragynine Reverses LPS-Induced Anxiety and Oxidative Stress in Rats via Modulation of Toll-Like Receptor 4 and Malondialdehyde (MDA).
AU - Hanisah Muhammad Faiz
AU - Suleiman Yunusa
AU - Muhammad Hazim Abdullah
AU - Zurina Hassan
PY - 2026
DA - 2026/10/15
JO - Tropical life sciences research
DO - 10.21315/tlsr2026.37.3.8
UR - https://europepmc.org/article/MED/42997699
AB - 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.
SN - 1985-3718
SN - 2180-4249
ER -