Dendrobium officinale Polysaccharides Inhibit CDCA-Induced Gastric Intestinal Metaplasia through Activating NRF2/HO-1 and Modulating HNF4α/CDX2 Signaling Pathway

Bile reflux (BR) was considered to be an independent risk factor for the development of precancerous gastric lesions and GC. Dendrobium officinale polysaccharides (DOP) show a novel potential in preventing the progress of gastric cancer. However, the specific mechanism of DOP that causes such activities remains a mystery. This study aimed to investigate the effects of DOP on chenodeoxycholic acid (CDCA)-induced gastric intestinal metaplasia and explore the underlying mechanisms. Different concentrations of DOP had no significant damage to normal GSE-1 cells and gastric intestinal metaplasia model cells by CCK-8 assay. After DOP treatment, the mRNA and protein expression of CDX2 ( $p$ < 0.01) and HNF4α ( $p$ < 0.01) were decreased, and HO-1 ( $p$ < 0.05) and TFF2 ( $p$ < 0.01) were increased. The NRF2 protein expression was slightly upregulated ( $p$ < 0.05), and H-DOP further promoted NRF2 protein expression in the nucleus ( $p$ < 0.05). Hence, our findings reveal that DOP could be used as a potential anti-inflammation supplement by activating NRF2/HO-1 and modulating the HNF4α/CDX2 signaling pathway to inhibit the progress of CDCA-induced gastric intestinal metaplasia.