Aflatoxin B1 (AFB1) is one of the
most harmful
and toxic mycotoxins in foods and feeds, posing a serious health risk
to both humans and animals, especially its hepatotoxicity. Nuclear
factor-erythroid 2-related factor 2 (Nrf2), an important nuclear transcription
factor, is generally recognized as a potential target for phytochemicals
to ameliorate liver injury. The current study sought to elucidate
the molecular processes by which licochalcone A (Lico A), a compound
derived from Xinjiang licorice Glycyrrhizainflate, protects against AFB1 toxicity. In vivo, male wild-type (WT) and Nrf2 knockout (Nrf2–/–) C57BL/6 mice were orally administered AFB1 at 1.5 mg/kg body weight (BW) with or without Lico A at 5
mg/kg. In vitro, AML12 cells were utilized to evaluate
the protective effect and mechanism of Lico A against the AFB1-induced hepatotoxicity. Our findings demonstrated that AFB1 caused severe hepatotoxicity, while Lico A treatment successfully
relieved the toxicity. Meanwhile, Lico A effectively improved liver
injury, inflammatory mediators, oxidative insults, apoptosis, liver
fibrosis, and pyroptosis, which contributed to the inhibition of toll
receptor 4 (TLR4)-NF-κB/MAPK and NOD-like receptors protein
3 (NLRP3)/caspase-1/GSDMD signaling pathway activation. Furthermore,
Lico A was able to enhance the Nrf2 antioxidant signaling pathway.
Intriguingly, Lico A still had a protective effect on AFB1-caused liver injury in mice via the inhibition of inflammation and
pyroptosis, while apoptosis and liver fibrosis were blocked in the
absence of Nrf2. To sum up, the present study first elucidated that
Lico A ameliorated AFB1-induced hepatotoxic effects and
its main mechanism involved the inhibitory effects on oxidative stress,
apoptosis, liver fibrosis, inflammation, and pyroptosis, which might
be partially dependent on the regulation of Nrf2. The work may enrich
the role and mechanism of Lico A’s resistance to liver injury
caused by various factors, and its application is promising.