Pharbitis nil Polysaccharide Ameliorate Ulcerative Colitis in Mice via Regulating Sphingolipid Metabolism

Abstract

Objective This study aimed to investigate the therapeutic effects of Pharbitis nil polysaccharides (PNP) on ulcerative colitis (UC) and elucidate the underlying mechanisms. Methods PNP were extracted using water extraction and alcohol precipitation. Acute UC was induced in mice by administration of 3% dextran sulfate sodium (DSS), and PNP was administered by oral gavage throughout the modeling period. Body weight, disease activity index (DAI), and colon length were assessed to evaluate colitis severity. Serum and colonic levels of inflammatory cytokines (IL-10, TNF-α, andsIgA) were measured by ELISA, and myeloperoxidase (MPO) activity was determined to evaluate intestinal inflammation. Fecal metabolomics and colonic sphingolipid metabolomics were performed using LC-MS/MS, followed by pathway enrichment analysis to identify the metabolic pathways involved in the protective effects of PNP. Results PNP effectively alleviated DSS-induced colitis in mice. Compared with the DSS group, the high-dose PNP (PNPH) increased body weight by 16.1%, reduced the DAI score by 38.9%, and restored colon length by 25.9%, indicating a significant improvement in disease manifestations. PNP also attenuated intestinal inflammation, as evidenced by decreased MPO activity in serum and colonic tissues, reduced TNF-α levels by 50.8%, and increased serum IL-10 levels by 176.5%. Furthermore, PNP improved immune function by normalizing the thymus and spleen indices and recoveringsIgA levels. Metabolomic analysis revealed that sphingolipid metabolism was the most significantly altered pathway associated with PNP treatment. PNP reversed DSS-induced disturbances in sphingolipid metabolism by regulating key metabolites, including ceramide (Cer), sphingomyelin (SM), and lactosylceramide (LacCer), and by restoring their abnormal accumulation in colonic tissues. Conclusions PNP alleviated DSS-induced colitis by suppressing intestinal inflammation and restoring immune homeostasis. Modulation of sphingolipid metabolism may be involved in the protective mechanisms of PNP against UC.