Abstract:This study explores the protective effects and mechanisms of Dendrobium officinale polysaccharides (Dendrobium officinale polysaccharide, DOP) on gallstone-induced gastric mucosal intestinal metaplasia (GIM) cell models using the histone deacetylase 3 (HDAC3)/hepatic nuclear factor 4α (HNF4α) pathway. A GIM model induced by 100 μM chenodeoxycholic acid (CDCA) was established, and cells were simultaneously treated with 400,200, and 100 μg/mL DOP interventions. The CCK8 assay was used to evaluate the effects of DOP and CDCA on GES-1 cells and the impact of DOP on CDCA-induced GIM model cell viability. Morphological changes in the CDCA-induced GIM model were observed using EdU staining, and the proliferation effects of DOP on the CDCA-induced GIM model were assessed through RT-PCR and Western Blot. The expression levels of tail-like homologous box gene (CDX2), mucin 2 (MUC2), hepatic nuclear factor 4α (HNF4α), G protein-coupled receptor (TGR5), farnesyltransferase receptor (FXR), and histone deacetylase 3 (HDAC3) genes and proteins were detected using RT-PCR and Western Blot. An HDAC3 overexpression GIM model was constructed, and the regulation of HNF4α by HDAC3 was investigated using Western Blot and CO-IP. The results show that DOP has no toxic side effects on GES-1 cells and is more effective than CDCA at concentrations above 100 μM. DOP does not significantly affect the viability or proliferation of cells in the CDCA-induced GIM model, but it helps maintain the normal phenotype of GES-1 cells. DOP can significantly downregulate the expression levels of genes and proteins such as CDX2, MUC2, HNF4α, TGR5, FXR, and HDAC3 (P<0.05, P<0.01, P<0.001), with HDAC3 and HNF4α showing an interaction. In summary, DOP is a potential HDAC3-targeted inhibitor that can prevent bile acid-induced gastric mucosal intestinal metaplasia by regulating the HDAC3/HNF4α signaling pathway. The research findings provide experimental foundations for further development of DOP and support clinical drug use with data.
