Cimicifuga foetida L. polysaccharide alleviates ulcerative colitis by inhibiting pyroptosis and regulating gut microbiota
TL;DR
The preliminary biological assessment suggests that the polysaccharide subfraction SM05 alleviated the symptoms of UC induced by DSS, and may be related to the activation of the Nrf2/Keap1 pathway, the inhibition of pyroptosis, and the regulation of the intestinal microbiota.
Abstract
Introduction Cimicifuga foetida L. is widely applied in the clinical treatment of ulcerative colitis (UC); however, its active components and mechanisms have not been deeply investigated. The objective of this study is to investigate the potential bioactive constituents of C. foetida L. for the treatment of UC, and elucidate its therapeutic mechanism. Methods The crude polysaccharide of C. foetida L. was extracted by hot water and purified by DEAE Sepharose™ Fast Flow column to obtain, and named SM05. The structure was determined by HPLC, FT-IR and SEM. The effect of polysaccharide (SM05) on the mouse UC model and its mechanism of action were investigated using a dextran sodium sulfate (DSS)-induced UC model. Changes in body weight, disease activity index, colon length, organ index, histopathological injury, cytokine expression and intestinal tight junction proteins were measured to evaluate the effect of SM05 on UC. IHC, RT-qPCR, and 16s rDNA sequencing were performed to elucidate the underlying mechanism. Results SM05 is mainly composed of mannose, glucose, galactose, and arabinose. SM05 exerts antioxidant effects by activating the Nrf2/Keap1 pathway, thereby inhibiting the NLRP3-induced pyroptosis pathway. This reduces abnormal intestinal cell death and the secretion of inflammatory cytokines, thus protecting the intestinal barrier and suppressing further inflammation. Additionally, SM05 modulates the gut microbiota structure in mice with ulcerative colitis by reducing pathogenic bacteria (e.g., Bacteroides and Desulfovibrio) that damage the intestinal barrier and increasing the abundance of beneficial bacteria (e.g., Akkermansia and Saccharibacteria), thereby alleviating the progression of ulcerative colitis. Discussion In the preliminary biological assessment, the polysaccharide subfraction SM05 alleviated the symptoms of UC induced by DSS. This effect may be related to the activation of the Nrf2/Keap1 pathway, the inhibition of pyroptosis, and the regulation of the intestinal microbiota.