Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway
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ABSTRACT:
ORGANISM(S): Mus musculus mouse gut metagenome
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 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 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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Project description:Obacunone, a natural limonoid compound abundantly distributed in citrus fruits, possesses various biological properties, such as antitumor, antioxidant, and antiviral activities. Recent studies suggested an anti-inflammatory activity of obacunone in vitro, but its efficacy on intestinal inflammation remains unknown. This study was designed to evaluate the effects and mechanisms of obacunone in ameliorating intestinal inflammation in a mouse model of ulcerative colitis (UC). We found that obacunone efficiently alleviated the severity of dextran sulfate sodium (DSS)-induced mouse UC by modulating the abnormal composition of the gut microbiota and attenuating the excessive activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling. The intestinal epithelial barrier was disrupted in DSS colitis mice, which was associated with activation of inflammatory signaling cascades. However, obacunone promoted the expression of tight junction proteins (TJP1 and occludin) and repressed the activation of inflammatory signaling cascades. In summary, our findings demonstrated that obacunone attenuated the symptoms of experimental UC in mice through modulation of the gut microbiota, attenuation of TLR4/NF-κB signaling cascades, and restoration of intestinal epithelial barrier integrity.
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Project description:Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder in the gastrointestinal tract. Here, we examined the pharmacological effects of ginsenoside Rg1, a natural compound with low bioavailability, on the acute experimental colitis mice induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Acute UC was induced in C57BL/6 mice by 2.5% DSS for 7 days, meanwhile, 2 mg/10 g b.w. ginsenoside Rg1 was administrated to treat the mice. Body weight, colon length, colon tissue pathology, and colon tissue inflammatory cytokines were assessed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. Global metabolomic profiling of the feces was performed, and tryptophan and its metabolites in the serum were detected. The results showed that Rg1 significantly ameliorated DSS-induced colonic injury and colonic inflammation. In addition, Rg1 also partly reversed the imbalance of gut microbiota composition caused by DSS. Rg1 intervention can regulate various metabolic pathways of gut microbiota such as valine, leucine, and isoleucine biosynthesis and vitamin B6 metabolism and the most prominent metabolic alteration was tryptophan metabolism. DSS decreased the levels of tryptophan metabolites in the serum, including indole-3-carboxaldehyde, indole-3-lactic acid, 3-indolepropionic acid, and niacinamide and Rg1 can increase the levels of these metabolites. In conclusion, the study discovered that Rg1 can protect the intestinal barrier and alleviate colon inflammation in UC mice, and the underlying mechanism is closely related to the regulation of gut microbiota composition and microbial tryptophan metabolism.
| S-EPMC9152015 | biostudies-literature
Project description:Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing interest in developing synbiotic therapies. This study investigated the effects of a novel synbiotic in an AIH mouse model. We found that this synbiotic (Syn) ameliorated liver injury and improved liver function by reducing hepatic inflammation and pyroptosis. The Syn reversed gut dysbiosis, as indicated by an increase in beneficial bacteria (e.g., Rikenella and Alistipes) and a decrease in potentially harmful bacteria (e.g., Escherichia-Shigella) and lipopolysaccharide (LPS)-bearing Gram-negative bacterial levels. The Syn maintained intestinal barrier integrity, reduced LPS, and inhibited the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathway. In addition, microbiome phenotype prediction by BugBase and bacterial functional potential prediction using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that Syn improved gut microbiota function involving inflammatory injury, metabolism, immune response, and pathopoiesia. Furthermore, the new Syn was as effective as prednisone against AIH. Therefore, this novel Syn could be a candidate drug for alleviating AIH through its anti-inflammatory and antipyroptosis properties that relieve endothelial dysfunction and gut dysbiosis. IMPORTANCE Synbiotics can ameliorate liver injury and improve liver function by reducing hepatic inflammation and pyroptosis. Our data indicate that our new Syn not only reverses gut dysbiosis by increasing beneficial bacteria and decreasing lipopolysaccharide (LPS)-bearing Gram-negative bacteria but also maintains intestinal barrier integrity. Thus, its mechanism might be associated with modulating gut microbiota composition and intestinal barrier function by inhibiting the TLR4/NF-κB/NLRP3/pyroptosis signaling pathway in the liver. This Syn is as effective as prednisone in treating AIH without side effects. Based on these findings, this novel Syn represents a potential therapeutic agent for AIH in clinical practice.
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