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This study aims to explore the neurotoxic effects of T-2 toxin and the protective mechanisms of betulinic acid.

May 26, 2026Veterinary Sciences0 citationsOpen Access

Betulinic Acid Ameliorates T-2 Toxin-Induced Neuroinflammation by Suppressing Oxidative Stress via Regulating Nrf2/NLRP3 Axis

Key Points

This study aims to explore the neurotoxic effects of T-2 toxin and the protective mechanisms of betulinic acid.
Evaluated T-2 toxin effects on the hippocampus and cerebral cortex in mice at 1 mg/kg/bw.
Assessed oxidative stress and inflammatory cytokine levels post-exposure to T-2 toxin.
Conducted molecular docking analyses to investigate betulinic acid interactions with key proteins.
T-2 toxin exposure caused significant neuronal damage and increased reactive oxygen species levels.
Betulinic acid restored Nrf2 expression and suppressed NLRP3 inflammasome activation, reducing inflammation.
BA showed strong binding affinity to proteins in the blood-brain barrier and the Nrf2/NLRP3 pathway.

Abstract

T-2 toxin is widely present in agricultural products and poses a significant neurotoxicity threat. Betulinic acid (BA), a natural triterpenoid, exhibits strong antioxidant and anti-inflammatory properties. However, its protective role against T-2 toxin-induced neuroinflammation remains poorly understood. This study aimed to elucidate the mechanisms underlying T-2 toxin-induced neurotoxicity and evaluate the therapeutic potential of BA. Our results demonstrated that T-2 toxin (1 mg/kg/bw) exposure caused significant pathological damage in the hippocampus and cerebral cortex. T-2 toxin also induced marked oxidative stress, reflected by elevated reactive oxygen species (ROS) accumulation. At the inflammatory level, T-2 toxin upregulated the mRNA expression of pro-inflammatory cytokines (Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6)) and altered anti-inflammatory IL-10 expression. In addition, T-2 toxin exhibited strong binding affinity for the tight junction proteins Occludin and Claudin-1 (docking energies of −4.41 and −5.53 kcal/mol, respectively), and molecular dynamics simulations confirmed stable protein–ligand interactions. At the molecular level, T-2 toxin suppressed Nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression, increased Kelch-like ECH-associated protein 1 (Keap1) expression, and activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway. Furthermore, molecular docking analysis revealed that BA displayed strong binding affinity to proteins associated with the blood–brain barrier and the Nrf2/NLRP3 signaling pathway. Collectively, these findings indicate that BA mitigates T-2 toxin-induced neuroinflammation through regulating the Nrf2/NLRP3 signaling pathway in mice. Not only do these results clarify a key mechanism of T-2 toxin-induced central nervous system injury, but they also highlight BA as a promising candidate for developing interventions targeting mycotoxin-related neurological disorders.

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