Ginsenoside Rg3 Ameliorates DSS-Induced Colitis by Inhibiting NLRP3 Inflammasome Activation and Regulating Microbial Homeostasis

Abstract

Ulcerative colitis (UC) is a recurrent inflammatory disease without a specific cure or treatment for improvement.Here, we investigated the potential therapeutic effect and mechanism of ginsenoside Rg3 (Gin Rg3) on UC. We constructed an in vitro cellular inflammatory model and a dextran sulfate sodium (DSS)-induced UC mouse model. We also used Gin Rg3, MCC950 (NLRP3 inhibitor), MSU (NLRP3 activator), and fecal transplantation (FMT) to intervene the model. The results showed that Gin Rg3 inhibited NLRP3 inflammasome activation, pyroptosis, and apoptosis in vitro and in vivo. DSS-induced changes in the abundance of gut microbiota at the phylum or genus level were partially restored by Gin Rg3. Furthermore, gin Rg3 affected intestinal metabolism in mice by inhibiting the activation of NLRP3 inflammasome. The gut microbiota treated with Gin Rg3 was sufficient to alleviate DSS-induced UC. In summary, Gin Rg3 alleviated DSS-induced UC by inhibiting NLRP3 inflammasome activation and regulating gut microbiota homeostasis.

Readily Available Oral Prebiotic Protein Reactive Oxygen Species Nanoscavengers for Synergistic Therapy of Inflammation and Fibrosis in Inflammatory Bowel Disease

“…We found that Candidatus Saccharimonas and Prevotellaceae-NK3B31 group had a strong positive correlation with mucus layer thickness and fecal SCFA levels but a negative correlation with MPO, MDA, and PAF levels (Figure J). In addition, Helicobacter were positively correlated with fecal SCFA levels, which is consistent with previous studies . In contrast, Eubacterium fissicatena group and Escherichia–Shigella showed strong positive correlations with inflammatory cytokines and negative correlations with SCFA levels, mucous layer thickness, and epithelial integrity.…”

“…In addition, Helicobacter were positively correlated with fecal SCFA levels, which is consistent with previous studies. 47 In contrast, Eubacterium f issicatena group and Escherichia− Shigella showed strong positive correlations with inflammatory cytokines and negative correlations with SCFA levels, mucous layer thickness, and epithelial integrity.…”

Polyphenol Extracts from Ziziphus jujuba Mill. “Junzao” Attenuates Ulcerative Colitis by Inhibiting the NLRP3 and MAPKs Signaling Pathways and Regulating Gut Microbiota Homeostasis in Mice

“…Significant modifications in the intestinal microbiota of NLRP3 knockout mice have been discovered in recent research, which suggests that NLRP3 inhibitors may be able to ameliorate UC by modulating intestinal microbiota. [49,50] Moreover, Liu et al [51] found that MCC950 (NLRP3 inhibitor) and MSU (NLRP3 activator) significantly change the intestinal microbiota composition in DSS-induced UC mice, indicating that the inhibition of NLRP3 inflammasome activation in mice regulates intestinal metabolism and further contributes to the prevention and alleviation of UC. In this study, the expression level of NLRP3 was positively associated with the relative abundance of Firmicutes, but positively c associated with the relative abundance of Proteobacteria (Figure 10).…”

Phenolics from Dendrobium officinale Leaf Ameliorate Dextran Sulfate Sodium-Induced Chronic Colitis by Regulating Gut Microbiota and Intestinal Barrier

“…It is generally accepted that intestinal microbiota and its metabolites have a significant impact on IBD. 43 The occurrence of colitis generally leads to a reduction of the diversity and abundance of gut microbiota. In our study, DOPL was able to reverse these trends.…”