Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway
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ABSTRACT:
ORGANISM(S): mouse gut metagenome Mus musculus
PROVIDER: GSE216435 | GEO | 2024/05/31
REPOSITORIES: GEO
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Project description:Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment.
| S-EPMC9697899 | biostudies-literature
Project description:Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway activation, and may be a promising therapeutic agent for UC treatment.
2024-05-31 | GSE216433 | GEO
Project description:Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway activation, and may be a promising therapeutic agent for UC treatment.
2024-05-31 | GSE216434 | GEO
Project description:Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway
| PRJNA893611 | ENA
Project description:Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway [16S]
| PRJNA893614 | ENA
Project description:Methyl Gallate Alleviates Acute Ulcerative Colitis by Modu-lating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway [RNA-seq]
| PRJNA893615 | ENA
Project description:Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.
| S-EPMC8339999 | biostudies-literature
Project description:Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the intestine, which is prone to recurrence and difficult to cure. Yiyi Fuzi Baijiang powder (YFBP), as a classic Chinese herbal formula, is commonly used in the clinical treatment of UC. However, its potential mechanism remains unclear. In this study, we investigated the mechanism by which YFBP exerts a therapeutic effect against UC. Firstly, we used network pharmacology to screen the active ingredients and potential targets of YFBP and constructed a “drug-ingredient-target” network. Based on bioinformatics, we searched for differentially expressed genes (DEGs) associated with UC and obtained common targets. The core targets of YFBP in the treatment of UC were identified using a protein-protein interaction (PPI) network, and molecular docking techniques were used to evaluate the binding energies of the core targets and corresponding ingredients. Enrichment analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that YFBP exerted therapeutic effects by regulating multiple inflammatory pathways including TLR4, NF-κB, and TNF. Secondly, an experimental study was carried out in vivo for verification. Our results demonstrated that YFBP could effectively improve the symptoms and intestinal pathological of UC rats. Further study showed that YFBP could significantly downregulate the expressions of TLR4 and p-NF-κB p65 in UC rats, inhibit the activation of NLRP3 inflammasome, reduce the levels of IL-1β and TNF-α, and then upregulate the expressions of tight junction proteins in intestinal epithelial cells. In addition, YFBP could improve the intestinal microbial community. In conclusion, our study revealed that YFBP had a good therapeutic effect on UC, and its mechanism might be related to the inhibition of the TLR4/NF-κB/NLRP3 inflammasome signaling pathway to repair intestinal epithelial barrier and the modulation of intestinal microbiota.
| S-EPMC9867587 | biostudies-literature
Project description:Pinocembrin, a plant-derived flavonoid, has a variety of pharmacological activities, including anti-infection, anti-cancer, anti-inflammation, cardiovascular protection, etc. However, the mechanism of pinocembrin on the anti-colitis efficacy remains elusive and needs further investigation. Here, we reported that pinocembrin eased the severity of dextran sulfate sodium (DSS)-induced colitis in mice by suppressing the abnormal activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway in vivo. In addition, the gut microbiota was disordered in DSS colitis mice, which was associated with a significant decrease in microbiota diversity and a great shift in bacteria profiles; however, pinocembrin treatment improved the imbalance of gut microbiota and made it similar to that in normal mice. On the other hand, in vitro, pinocembrin down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, pinocembrin competitively inhibited the binding of LPS to myeloid differentiation protein 2 (MD2), thereby blocking the formation of receptor multimer TLR4/MD2·LPS. Furthermore, pinocembrin dose-dependently promoted the expression of tight junction proteins (ZO-1, Claudin-1, Occludin and JAM-A) in Caco-2 cells. In conclusion, our work presented evidence that pinocembrin attenuated DSS-induced colitis in mouse, at least in part, via regulating intestinal microbiota, inhibiting the over-activation of TLR4/MD2/NF-κB signaling pathway, and improving the barriers of intestine.
| S-EPMC7391130 | biostudies-literature
Project description:Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease affecting the gastrointestinal tract. Although paeonol has been used for treating UC due to its anti-inflammatory and antioxidant effects, the underlying mechanisms remain unclear. In this study, we investigated the mechanisms of paeonol's action on UC by conducting in-vitro and in-vivo studies using NCM460 cells and RAW264.7 cells, and the DSS-induced mice colitis model. The in vitro studies demonstrate that paeonol exerts inhibitory effects on the activation of the NF-κB signaling pathway through upregulating PPARγ expression, thereby attenuating pro-inflammatory cytokine production, reducing reactive oxygen species levels, and promoting M2 macrophage polarization. These effects are significantly abrogated upon addition of the PPARγ inhibitor GW9662. Moreover, UC mice treated with paeonol showed increased PPARγ expression, which reduced inflammation and apoptosis to maintain intestinal epithelial barrier integrity. In conclusion, our findings suggest that paeonol inhibits the NF-κB signaling pathway by activating PPARγ, reducing inflammation and oxidative stress and improving Dss-induced colitis. This study provides a new insight into the mechanism of treating UC by paeonol.
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