Work

Dihydromyricetin attenuates aflatoxin B1-induced IEC-6 cell damage and intestinal damage in mice by activating the Nrf2/HO-1 signaling pathway and modulation of gut microbiota.

Year: 2025

Type: article

Abstract: Aflatoxin B1 (AFB1) is commonly found in food and feed and has toxic effects on the gastrointestinal tract, impacting public health and livestock development. Dihydromyricetin (DHM) is a natural oxanthrone that has been proven to have significant protective effects on the intestines. This study aimed to elucidate the potential mechanism of DHM alleviating AFB1 exposure-intestinal toxicity in mice. In vitro , rat small intestinal crypt epithelial cells (IEC-6) were treated with aflatoxin B1 (0–120 μmol/L) and DHM (0–320 μmol/L). In vivo , BALB/c mice were divided into four groups: control, AFB1(200 μg/kg), DHM-L (AFB1 + DHM-100 mg/kg), and DHM-H (AFB1 + DHM-200 mg/kg), and gavaged for 30 days. The results showed that the viability of IEC-6 cells decreased with increasing mycotoxin concentration. In addition, RT-qPCR, Western blot, and immunofluorescence results showed that DHM significantly reversed AFB1-induced down-regulation of tight junction proteins, inhibition of the Nrf2/HO-1 signaling pathway, increased expression levels of Caspase-3, Bax, and inflammatory factors, and decreased Bcl-2 levels. In in vivo experiments, we also found that chorionic villus height and crypt depth, expression levels of tight junction proteins, Nrf2/HO-1 signaling pathway, Bax, Bcl-2, Caspase-3, and inflammatory factors, as well as intestinal microbiota, were significantly adversely affected in AFB1-exposed mice. However, the microbial diversity was significantly improved and enhanced by the DHM intervention. In conclusion, DHM intervention attenuated aflatoxin B1-induced intestinal injury by remodeling the gut microbiota, activating the Nrf2/HO-1 signaling pathway, strengthening the intestinal barrier, reducing apoptosis, and inhibiting the release of pro-inflammatory cytokines. • DHM attenuated intestinal mucosal injury by regulating the tight junction protein. • DHM attenuated intestinal mucosal injury by activating the Nrf2/HO-1 signaling pathway and controlling ROS content. • DHM controlled the content of Bax and Caspase-3 and up-regulated the level of Bcl-2 to prevent AFB1-induced apoptosis. • DHM effectively attenuated AFB1-induced inflammatory factor levels of IL-1β, IL-6, TNF-α, NF-kB, and p-NF-kB in the intestine. • DHM corrected AFB1-induced gut microbiota dysbiosis and enhanced microbial diversity in the gut.

Source: Journal of Functional Foods

DOI: 10.1016/j.jff.2025.106716