Acrylamide (ACR) generated in carbohydrate-rich foods during thermal processing has been demonstrated to exhibit hepatotoxicity. As one of the most consumed flavonoids with diet, quercetin (QCT) possesses the ability to protect against ACRinduced toxicity, albeit its mechanism is unclear. Herein, we discovered that QCT alleviated ACR-induced elevated levels of reactive oxygen species (ROS), AST, and ALT in mice. RNA-seq analysis revealed that QCT reversed the ferroptosis signaling pathway upregulated by ACR. Subsequently, experiments indicated that QCT inhibited ACR-induced ferroptosis through the reduction of oxidative stress. With autophagy inhibitor chloroquine, we further confirmed that QCT suppressed ACR-induced ferroptosis by inhibiting oxidative stress-driven autophagy. Additionally, QCT specifically reacted with autophagic cargo receptor NCOA4, blocked the degradation of iron storage protein FTH1, and eventually downregulated the intracellular iron levels and the consequent ferroptosis. Collectively, our results presented a unique approach to alleviate ACR-induced liver injury by targeting ferroptosis with QCT.

Intestinal stem cells (ISCs) are essential to maintain intestinal epithelial regeneration and barrier function. Our previous work showed that glucomannan from Aloe vera gel (AGP) alleviated epithelial damage, but the mechanism was still elusive. Herein, RNA-sequencing analysis showed that proliferation and differentiation of intestinal epithelial cells as well as the canonical Wnt pathway were involved in this process. Further experiments exhibited that AGP promoted nuclear translocation of β-catenin and expression of transcription factor 7, increased the number of Lgr5 + ISCs, and differentiated epithelial cells in mice colon. Intriguingly, AGP reversed the inhibition of IEC-6 cells proliferation induced by an inhibitor of the canonical Wnt pathway. Hence, this study implied that AGP promoted proliferation and differentiation of colon stem cells via Wnt/β-catenin signaling, which subsequently facilitated the regeneration of epithelial cells and alleviated colitis in mice. It may provide new insights into the role of polysaccharides in regulating intestinal homeostasis and relieving intestinal injury.

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