Flavonoids as multi-target protective agents against aflatoxin B1 toxicity: mechanistic convergence and translational challenges.

Aflatoxin B1 (AFB1) is the most widespread and toxic mycotoxin found in food and feed. It is both chemically and physically stable and shows resistance to degradation during processing. AFB1 can cause damage to multiple organs, including the liver, immune system, nervous system, kidneys, reproductive system, intestines, and genetic material. Therefore, the development of a safe and effective antidote is urgently needed. Flavonoids are a class of natural polyphenols widely found in fruits, vegetables, and herbs, which can mitigate AFB1-induced organ toxicity through various mechanisms. However, the precise molecular mechanisms responsible for their detoxifying actions have yet to be systematically characterized and fully elucidated. Therefore, this review systematically summarizes the protective effects of flavonoids (including flavones, flavonols, dihydroflavones, dihydroflavonols, isoflavones, flavanols, chalcones, and anthocyanins, among others) against AFB1-induced multi-organ toxicity. These flavonoids primarily exert their protective effects by targeting multiple key pathways, including activation of the Nrf2/ARE antioxidant system, inhibition of the NF-κB/NLRP3 inflammatory axis, regulation of the Bax/Bcl-2/Caspase-3 apoptotic cascade, suppression of ferroptosis via the GPX4/xCT/ACSL4 pathway, and modulation of the gut-liver/spleen axis. This review provides a mechanistic basis for the development of flavonoid-based AFB1 detoxification strategies.