BACKGROUND: Ulcerative colitis (UC) is a form of inflammatory bowel disease and a serious and increasingly prevalent global health concern. Cistanche tubulosa (Schenk) R. Wight is a traditional Chinese medicine containing polysaccharides and used to regulate immunity and replenish essence to alleviate UC. However, the mechanism of action of C. tubulosa polysaccharides (CTCA) for the treatment of UC needs further validation.
OBJECTIVE: The study aimed to investigate the protective effect of CTCA in mice with chronic UC and to explore its underlying mechanisms through short-chain fatty acid (SCFA) analysis and 16S rRNA sequencing.
METHODS: In vitro experiments using RAW264.7 cells and in vivo studies using a C57BL/6 chronic UC mouse model were conducted to examine the potential role of CTCA in alleviating inflammation. 16S rRNA sequencing was used to evaluate the effect of CTCA on the gut microbiota, and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis was performed to predict potential pathways involved in its therapeutic effects. SCFA analysis, quantitative PCR (qPCR), and Western blotting (WB) were used to validate the pathway predictions from KEGG analysis. Pseudo-germfree mice experiments were used to validate the impact of the gut microbiota on the therapeutic effects of CTCA in UC.
RESULTS: In vitro and in vivo experiments have demonstrated the potential of CTCA in treating chronic UC induced by dextran sulfate sodium (DSS). 16S rRNA sequencing results demonstrated that CTCA can restore intestinal microbial homeostasis in UC mice. KEGG analysis revealed that carbohydrate metabolism and immune regulation are involved in the therapeutic efficacy of CTCA. qPCR and WB experiments verified that CTCA act through modulation of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) signalling pathway. The combined analyses suggested a strong correlation between gut microbiota and CTCA for the treatment of UC. Pseudo-germfree mice experiments validated that the anti-inflammatory and gut-protective functions of CTCA in UC were limited in the absence of the gut microbiota.
CONCLUSIONS: CTCA protects the intestinal mucosal barrier and alleviates inflammation, thereby ameliorating DSS-induced chronic ulcerative colitis in mice. This effect is strongly correlated with CTCA's regulation of SCFA metabolism mediated by the gut microbiota and the MAPK/NF-κB pathway. CTCA holds potential application as a dietary supplement to modulate gut microecology as a clinical option for the treatment of UC.
