Multi-omics analysis reveals the pre-protective mechanism of Dendrobium flexicaule polysaccharide against alcohol-induced gastric mucosal injury.

Dendrobium flexicaule (DF) is an endemic plant primarily found in the mountains of central China with important medicinal and edible values. In traditional Chinese medicine, DF has the effects of nourishing stomach and "Yin", and clearing heat. At present, no studies have explored the mechanisms by which Dendrobium flexicaule polysaccharides (DFP) exert pre-protect effects against alcohol-induced gastric mucosal injury. In this study, DFP (367.478 kDa) was extracted through water extraction and ethanol precipitation, and composed of mannose (79.89 %), glucose (19.05 %), xylose (0.42 %), arabinose (0.33 %), and galactose (0.31 %). A rat model of alcohol-induced gastric mucosal injury was established to evaluate the pre-protective effects of DFP. Histological analysis, using hematoxylin-eosin staining, revealed that DFP alleviated gastric mucosal congestion and redness. Furthermore, DFP downregulated the expression of IL-6, IL-1β, MPO and MDA, while upregulating the expression of PGE2, GSH and SOD. Immunofluorescence analysis demonstrated that DFP upregulated the expression of ZO-1 and Occludin, thereby improving gastric barrier function. Multi-omics analysis revealed its regulation of the complement and coagulation cascade signaling pathway, as well as the propanoate metabolism pathway. Immunohistochemical analysis further confirmed that DFP significantly down-regulated the expression of C3, VTN, F2, Serpind1, CPB2, FGA and VWF. Overall, this study offers novel insights into the pre-protective effects and mechanisms of DFP against alcohol-induced gastric mucosal injury, laying the groundwork for the development of DF based therapeutic resources.