Transcriptome Analysis Reveals the Regulatory Role of Jianpi Huazhi Wan (JPHZW) in Alleviating DSS-Induced Ulcerative Colitis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE293468 | GEO | 2026/04/01
REPOSITORIES: GEO
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Project description:Evodiamine (Evo), a kind of alkaloid mostly extracted from Tetradium ruticarpum, which has many pharmacological functions, such as antidiarrheal, antiemetic, and antiulcer effects. In this study, the effects of Evo were investigated in DSS-induced ulcerative colitis (UC) mice and C57BL/6-ApcMinC/Gpt mice with colorectal cancer (CRC). The results showed Evo not only sup-pressed the weight loss and the shorthen of colon, decreased disease activity index (DAI) and ameliorated the pathological alteration of colon in UC mice, but also inhibited the numbers and sizes of colonic tumor of ApcMinC/Gpt mice. Meanwhiles, Evo regulated nuclear factor-kappa B (NF-κB) related signal pathways to mediate various cytokines such as interleukins (Ils), tumor necrosis factor-α (TNF-α) to achieve anti-inflammatory and anti-tumor effects. In SW480 and Caco cells, Evo reduced the cell viabilities, promoted the mitochondrial membrane potential (MMP) and caused the over-accumulation of intracellular reactive oxygen species (ROS). Theoretical evi-dences indicated Evo binding NF-κB may be useful to contain ordered domain (α helix) in NF-κB, which can induce NF-κB to perform its function. Our results provide experimental and theoretical evidence that Evo might be promising and effective treatments in clinics for UC and CRC.
2022-05-20 | PXD027745 | Pride
Project description:<p>Background: Bupleurum chinense DC polysaccharide (BCP) demonstrates a significant role in ameliorating gastric ulceration and enhancing intestinal barrier function, and have broad medicinal value. Nevertheless, the therapeutic effects and mechanisms in ulcerative colitis (UC) remain to be elucidated. </p><p>Purpose: The protective effect of BCP on dextran sulfate sodium (DSS)-induced UC and the related mechanisms will be discussed.</p><p>Methods: The efficacy of BCP was evaluated using a 2.5% DSS-induced UC model. The mechanistic contribution of the gut microbiota to the therapeutic efficacy of BCP in UC was elucidated through 16S rRNA sequencing, microbiota depletion experiment and fecal microbiota transplantation (FMT) experiments. Non-targeted metabolomics analysis was used to identify its potential metabolic pathways and core signaling pathways. In vitro, Caco-2 and NCM460 cells were treated with LPS to induce inflammation for assessing the effects of BCP.</p><p>Results: BCP significantly alleviated UC injuries, including decreasing body weight loss and disease activity index (DAI), and increasing colon length. Moreover, BCP significantly reduced inflammatory cytokine levels and improved histopathological damage in the colon. BCP promoted tight junction proteins (TJ proteins) expression, facilitated MUC2 secretion, and helped alleviate DSS-induced intestinal barrier damage. BCP could improve the gut microbiota changes, and BCP’s therapeutic effects on UC were mediated through the gut microbiota in vivo experiment. Additionally, metabolomics analysis revealed that BCP could impact the tryptophan metabolism pathway and target the AHR-NF-κB signaling pathway to improve UC.</p><p>Conclusion: This study reveals that BCP improves UC through modulation of the gut microbiota and the tryptophan metabolism via NF-κB axis.</p>
2026-02-01 | MTBLS13814 | MetaboLights
Project description:Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signaling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM-1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM-1-positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM-1, CD31, and immune cell markers (CD8, CD68, CD163, and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulfate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti-MAdCAM-1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM-1-positive vessels and infiltrating CD8+, CD68+, and CD163+ immune cells was significantly higher in dysplasia/colitic cancer than in normal, SCRC, and UC mucosa. In AOM/DSS mice, the anti-MAdCAM-1 antibody reduced the number, mean diameter, depth of tumors, Ki67 positivity, number of CD8+, CD68+, and CD163+ immune cells, and the IL-6/p-STAT3 and TNF-α/NF-κB signaling. Our results indicate that targeting MAdCAM-1 is a promising strategy for controlling not only UC severity, but also carcinogenesis and tumor progression by regulating inflammation/immune cell infiltration in patients with UC.
2023-07-10 | GSE236524 | GEO
Project description:Background: Mesenchymal stem cells (MSCs) can be acquired from medical waste. MSCs are easily expanded and have multiple functions, including anti-inflammatory effects. We evaluated the effects of human adipose tissue-derived MSCs (AD-MSCs) and umbilical cord tissue-derived MSCs (UC-MSC) in a dextran sulfate sodium (DSS)-induced mouse model. Methods: Human AD-MSCs and UC-MSCs (1 × 106 cells) were injected intravenously into a 7-day DSS-induced colitis model. The therapeutic effects of cell origin, injection timing, and supernatants obtained from MSC cultures were evaluated. We also analyzed mRNA expression in MSCs, tissues, and intestinal flora. Results: AD-MSCs and UC-MSCs had strong anti-inflammatory effects when injected on day 3 in a mouse model. On day 11, mRNA levels of inflammatory factors in colon tissues were significantly decreased after injection of MSCs on day 3. Supernatants from MSCs culture decreased mRNA levels of tumor necrosis factor (Tnf)-α, but had reduced therapeutic effects compared with MSC cell injection. RNA sequencing using colon tissues obtained the day after cell injection revealed changes in the TNF-α/nuclear factor-κB and T-cell receptor signaling pathways. Additional analyses showed that several factors, including chromosome 10 open reading frame 54, stanniocalcin-1, and TNF receptor superfamily member 11b were increased in MSCs after adding serum from DSS colitis mice. Furthermore, both AD-MSCs and UC-MSCs maintained the balance of intestinal flora. Conclusion: AD-MSCs and UC-MSCs showed therapeutic effects against inflammation after early cell injection while maintaining the intestinal flora. Although supernatants showed therapeutic effects, cell injection was more effective against inflammation.
2019-09-11 | GSE137173 | GEO
Project description:Background: Mesenchymal stem cells (MSCs) can be acquired from medical waste. MSCs are easily expanded and have multiple functions, including anti-inflammatory effects. We evaluated the effects of human adipose tissue-derived MSCs (AD-MSCs) and umbilical cord tissue-derived MSCs (UC-MSC) in a dextran sulfate sodium (DSS)-induced mouse model. Methods: Human AD-MSCs and UC-MSCs (1 × 106 cells) were injected intravenously into a 7-day DSS-induced colitis model. The therapeutic effects of cell origin, injection timing, and supernatants obtained from MSC cultures were evaluated. We also analyzed mRNA expression in MSCs, tissues, and intestinal flora. Results: AD-MSCs and UC-MSCs had strong anti-inflammatory effects when injected on day 3 in a mouse model. On day 11, mRNA levels of inflammatory factors in colon tissues were significantly decreased after injection of MSCs on day 3. Supernatants from MSCs culture decreased mRNA levels of tumor necrosis factor (Tnf)-α, but had reduced therapeutic effects compared with MSC cell injection. RNA sequencing using colon tissues obtained the day after cell injection revealed changes in the TNF-α/nuclear factor-κB and T-cell receptor signaling pathways. Additional analyses showed that several factors, including chromosome 10 open reading frame 54, stanniocalcin-1, and TNF receptor superfamily member 11b were increased in MSCs after adding serum from DSS colitis mice. Furthermore, both AD-MSCs and UC-MSCs maintained the balance of intestinal flora. Conclusion: AD-MSCs and UC-MSCs showed therapeutic effects against inflammation after early cell injection while maintaining the intestinal flora. Although supernatants showed therapeutic effects, cell injection was more effective against inflammation.
2019-11-19 | GSE136397 | GEO
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, characterized by recurring mucosal inflammation. Current evidence suggests that dysbiosis may drive the disease, but mechanistic links remain incompletely understood. To further investigate the host-microbiome interactions, three UC-induction methods were used on a pseudo germ-free mouse model: (1) DSS, (2) fecal microbiota transplantation (FMT) from a UC patient, and (3) combination of both DSS and FMT simultaneously. Disease severity (DAI), immune cell profiles (flow cytometry), colon transcriptomics (RNA sequencing), and microbiota composition (16S rRNA sequencing) were assessed. Our study revealed distinct effects of DSS and FMT on experimental colitis. DSS had a more pronounced impact on disease severity, while FMT exerted a stronger influence on several immune populations and downregulation of genes associated with tight junctions and mucins. Microbiome analysis demonstrated distinct compositional profiles across all experimental groups. The combined FMT and DSS model exhibited features of both induction methods, resulting in exacerbated clinical scores, barrier dysfunction, and inflammatory responses. Our study provides valuable insight into host–microbiome interactions in UC and introduces a dual-hit approach that may more accurately recapitulate its multifactorial pathogenesis than DSS alone.
2025-08-20 | GSE305760 | 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 | 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:Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that predisposes to colorectal cancer (CRC) and is modeled in mice by administration of dextran sodium sulfate (DSS) in drinking water. There are two isoforms of STAT3, STAT3α is pro-inflammatory and anti-apoptotic, while STAT3β has opposing effects on STAT3α. We examined the severity of DSS-induced colitis in transgenic-mice expressing only STAT3α ( / ) and in wild-type (WT) mice administered C188-9, a small molecule direct-inhibitor of STAT3. While manifestations of DSS-induced UC, such as mortality, weight-loss, rectal-bleeding, diarrhea, and colon-shortening, were exacerbated in / transgenic versus cage-control WT mice, all were prevented by C188-9 treatment of WT mice. C188-9 treatment also increased apoptosis of pathogenic CD4+T-cells, reduced colon-levels of IL17-positive cells, down-modulated mRNA-levels of STAT3-genes involved in inflammation, apoptosis-prevention, and colorectal-cancer-metastases. These are the only studies showing efficacy of Thus small-molecule targeting of STAT3 may be a useful novel approach in treating UC and preventing UC-associated colorectal-cancer. We performed genome-wide microarray expression profiling to gain greater understanding of the mechanisms involved in the protective effect of C188-9 in DSS-induced colitis, we examined mRNA levels in the colon of mice receiving DSS or plain water, without or with C188-9 treatment.
2019-07-24 | GSE117355 | GEO
Project description:<p>Background: Ulcerative colitis (UC) is a significant and challenging condition in the digestive system, necessitating the development of effective therapeutic interventions. The Daifu decoction (DFD) is derived from the Lizhong decoction, a classic traditional Chinese Medicine (TCM) formula used to treat digestive diseases. Previous studies have found that DFD has a clear therapeutic effect on UC. This study aimed to investigate the underlying mechanisms of DFD in UC treatment.</p><p>Methods: A mouse model of dextran sulfate sodium (DSS)-induced UC was established, and mice were treated with DFD using the concentrations 1.6 g/kg/d, 3.2 g/kg/d, and 6.4 g/kg/d for 7 days. H&E and AB-PAS staining, ELISA, qPCR, and immunofluorescence were selected to assess the role of DFD in alleviating colitis and improving intestinal barrier damage. In addition, untargeted metabolomics and transcriptomics helped investigate the potential mechanism of DFD against UC, 16S rRNA sequencing evaluated the characteristics of the gut microbiota. The key target and downstream molecules were verified by molecular docking, molecular dynamics simulation, qPCR, western blotting, and immunohistochemistry.</p><p>Results: DFD prevented goblet cell loss, downregulated proinflammatory factors in serum, and improved tight junction mRNA and protein expression in colon tissue. Furthermore, DFD decreased the proportion of pathogenic microbes, while increasing the microbiota diversity and the proportion of beneficial bacterial. The integrated multi-omics analysis revealed that PRKCG was the key target of DFD to improve UC. Molecular docking and molecular dynamics simulations further confirmed that the active components of DFD could bind to PRKCG stably. The results of qPCR, western blotting, and immunohistochemistry revealed that DFD could regulate PKCγ/ERK/NF-κB pathway.</p><p>Conclusion: DFD can exert therapeutic effects on UC by regulating the PKCγ/ERK/NF-κB signaling pathway and the gut microbiota to restore the intestinal barrier and decrease the secretion of proinflammatory cytokines.</p>
2026-03-18 | MTBLS13973 | MetaboLights