Xanthohumol alleviates T2DM-induced liver steatosis and fibrosis by mediating the NRF2/RAGE/NF-κB signaling pathway

Hyperglycemia-associated advanced glycation end products (AGEs) and the receptor for AGE (RAGE) contribute to nonalcoholic fatty liver disease (NAFLD). Xanthohumol (XH) exhibits protective activities against liver diseases. Aim: To investigate the effects of XH on Type II diabetes mellitus (T2DM)-induced liver steatosis and fibrosis. Methods: NAFLD rat models were duplicated. Biomolecular markers were detected. Quantitative real-time PCR (RT-PCR) and western blot were used to detect mRNA and protein expression. Immunofluorescence assays were employed to identify the subcellular locations. Results: XH significantly ameliorated hyperglycemia and hyperlipidemia in rats. XH attenuated the expression of RAGE and NF-κB signaling. XH significantly alleviated inflammation and oxidation by upregulating NRF2 expression. Knockdown of NRF2 blocked XH protection in hepatocytes. Conclusion: XH protected against T2DM-induced liver steatosis and fibrosis by mediating NRF2/AGE/RAGE/NF-κB signaling.