Natural Phenolic Compounds against Trichothecenes: From Protective Mechanisms to Future Perspectives.

Trichothecenes (TCNs), Fusarium-derived mycotoxins exemplified by deoxynivalenol and T-2 toxin, threaten global health through multisystem toxicity and widespread contamination. Natural phenolic compounds (NPCs), leveraging their intrinsic safety and natural abundance, demonstrate multimechanistic efficacy in counteracting TCN toxicity. This article reviews both domestic and international research on the protective mechanisms of NPCs against TCN-induced toxicity. NPCs exert protective effects against TCN toxicity through multitiered mechanisms: (1) molecular regulation via Nrf2-centric antioxidant activation and MAPK/NF-κB inflammatory axis suppression, coupled with coordinated inhibition of programmed cell death pathways (apoptosis/ferroptosis/pyroptosis) and autophagy modulation, where GPX4 emerges as a critical ferroptosis regulator; (2) restoring microbiome balance, enhancing intestinal barrier function, and optimizing nutrient transport. Gut microflora may also serve as an additional target for NPCs in mitigating the toxicity of TCNs. NPCs further inhibit Fusarium proliferation and mycotoxin biosynthesis. While there is demonstrated potential for food safety and sustainable feed development, critical challenges persist in bioavailability optimization, pharmacokinetic profiling, and microbiota-metabolite crosstalk. This analysis advances NPC-based strategies for mycotoxin detoxification and sustainable agriculture.