Isoliquiritigenin attenuates high-fat diet-induced intestinal damage by suppressing inflammation and oxidative stress and through activating Nrf2

This study examined if isoliquiritigenin (ISL) attenuates high-fat diet (HFD)-induced intestinal damage and if this involves modulating Nrf2. Rats included 5 groups (n = 8/group): control (vehicle), ISL, HFD, HFD + ISL, and HFD + ISL + brusatol (an inhibitor of Nrf2). Treatments with the vehicle and ISL (30 mg/kg) were given orally. With no effect on intestinal lipids, ISL improved the duodenal structure in HFD rats and reduced the duodenal levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-6, macrophage chemoattractant protein-1, and nuclear levels of NF-kappa B p65. Also, ISL increased the intestinal levels of superoxide dismutase, catalase, glutathione, and the cytoplasmic and nuclear levels of Nrf2. Furthermore, ISL lowered circulatory levels of lipopolysaccharides, deactivated the myosin light chain kinase (MLCK), and increased mRNA claudin-1, occluding, and zonula occludens-1. All these effects were prevented by co-treatment of brusatol. In conclusion, ISL is a potent activator of Nrf2 intestinal inflammatory disorders.