Steamed garlic attenuates ulcerative colitis in mice by modulating the MAPK signaling pathway and improving intestinal homeostasis.

Pharmacodynamic and pharmacokinetic study of Shaoyao Gancao decoction for repairing intestinal barrier damage in ulcerative colitis

This study aimed to evaluate the effects of trilobatin (TLB) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and further explore the underlying mechanisms from the perspectives of signaling pathway and gut microbiota. A mouse model of UC was established using DSS. Trilobatin was administered via oral gavage. Disease severity was assessed based on body weight, disease activity index (DAI), colon length, histological detection, inflammation markers, and colonic mucosal barrier damage. Alternations in the NF-κB and PI3K/Akt pathways were detected by marker proteins. High-throughput 16S rRNA sequencing was performed to investigate the gut microbiota of mice. In the DSS-induced UC mice, TLB (30 μg/g) treatment significantly increased the body weight, reduced the DAI score, alleviated colon length shortening, improved histopathological changes in colon tissue, inhibited the secretion and expression of inflammation factors (TNF-α, IL-1β, and IL-6), and increased the expression of tight-junction proteins (ZO-1 and occludin). Furthermore, TLB (30 μg/g) treatment significantly suppressed the activation of NF-κB pathway and altered the composition and diversity of the gut microbiota, as observed in the variations of the relative abundances of Proteobacteria, Actinobacteriota, and Bacteroidota, in UC mice. TLB effectively alleviates DSS-induced UC in mice. Regulation of the NF-κB pathway and gut microbiota contributes to TLB-mediated therapeutic effects. Our study not only identified a novel drug candidate for the treatment of UC, but also enhanced our understanding of the biological functions of TLB.

Clinically, Qing-Re-Hua-Shi Decoction (QRHSD) has been clinically used to treat ulcerative colitis (UC) with satisfactory outcomes and minimal side effects. However, its molecular mechanisms remain unclear. This study investigates the effects of QRHSD on DSS-induced colitis in mice, employing multi-omics analyses, including RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology analysis. The chemical composition of QRHSD was analyzed using quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A UC mice model was induced by 3% DSS for 7 days. The effects and mechanisms of QRHSD on UC were evaluated via hematoxylin and eosin, immunofluorescence assay, flow cytometry, western blot, RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology. Correlation analyses and validation experiments explored links between transcriptomic, microbiome, metabolomic profiles, and UC-related clinical indices. UPLC-Q-TOF/MS identified 55 compounds in QRHSD. QRHSD significantly reduced clinical activity, histological changes, and inflammatory factors in UC mice, regulated Th17/Treg balance, and enhanced intestinal barrier integrity. 16S rRNA analysis showed that QRHSD altered gut microbiota composition, increasing beneficial bacteria (e.g., Lactobacillus) and decreasing harmful bacteria (e.g., Morganella). Non-targeted metabolomics revealed 507 metabolites associated with UC amelioration, enriched in pathways like bile secretion, ABC transporters, and amino acid biosynthesis. RNA-seq analysis, network pharmacology, and experimental verification showed that QRHSD significantly regulated key signaling pathways, including PI3K/AKT, NF-κB, and MAPK signaling pathways. Finally, correlation analysis highlighted connections among UC-related clinical factors, gut microbiota, and metabolites. QRHSD could modulate the gut microbiota, metabolic homeostasis, and multiple signal pathways in the treatment of DSS-induced UC, revealing the mechanism of traditional Chinese medicine therapy for UC.

ObjectiveThis research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation.MethodsTo investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments.ResultsAdministering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome.Conclusion7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.

Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.

Baitouweng Tang alleviates dextran sulfate sodium-induced ulcerative colitis in mice: a network pharmacology combined with experimental study.

Total flavonoid of vine tea reduces neutrophil extracellular traps release by inhibiting PI3K-AKT-mTOR signaling pathway to treat ulcerative colitis

Novel applications of Yinhua Miyanling tablets in ulcerative colitis treatment based on metabolomics and network pharmacology

ObjectiveThis study evaluated the effects of sauchinone on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model and investigated the underlying mechanisms of the downstream pathway and gut microbiota.MethodsThe UC mice model was induced by DSS. The disease phenotypes were determined through pathological symptoms (body weight and disease activity index score), inflammation markers (histological and inflammatory factor detections), and colonic mucosal barrier damage (detection of tight junction proteins). The level of the NF-κB pathway was detected through marker proteins. Database and bioinformatics analyses were used to predict sauchinone-mediated downstream molecules that were previously identified by expression analysis. Mouse feces were collected to detect the V3–V4 region of the 16S rRNA gene.ResultsIn DSS-induced UC mice, sauchinone alleviated pathological symptoms, inhibited inflammation, and prevented mucosal barrier damage. Sauchinone further inhibited the NF-κB pathway by upregulating NAD (P) H dehydrogenase [quinone] 1 (NQO1) in DSS-induced UC mice. Moreover, sauchinone regulated the diversity and composition of the gut microbiota in mice, stimulating the growth of Firmicutes and inhibiting the growth of Proteobacteria and Bacteroidetes.ConclusionTherefore, sauchinone exerted therapeutic effects on UC in mice by regulating the NQO1/NF-κB pathway and altering the gut microbiota. This provides a theoretical basis for developing sauchinone as a therapeutic agent and extends our understanding of its bioactivity.

Chitosan-coated artesunate protects against ulcerative colitis via STAT6-mediated macrophage M2 polarization and intestinal barrier protection

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by changes in the metabolism of short chain fatty acids (SCFAs), dysregulation of gut microbiota, and an imbalance of Treg/Th17. Herein, we explore the effects of the Ento-A (an alcohol extract of Periplaneta americana L.) on a mouse model of UC. First, a chronic and recurrent UC model was constructed in BALB/c mice by 2.2% DSS administration. UC mice were continuously treated for 14 days with Ento-A (50, 100, 200 mg/kg, i.g.) or a negative control. Ento-A alleviated many of the pathological changes observed in UC mice, such as body weight loss, disease activity index, changes in colon length, and colonic mucosal damage index. Ento-A also decreased levels of proinflammatory cytokines (IL-1β, IL-6, IL-17A, and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β1) and repaired the intestinal mucosal barrier. Additionally, Ento-A regulated the proportions of Th17 cells, and Treg cells in mesenteric lymph nodes harvested from treated mice (as assessed by Flow cytometry), and the expression levels of IL-17A and Foxp3 in colon (as assessed by immunohistochemistry). 16 S rRNA gene sequencing revealed that Ento-A regulated gut microbiota. GC-MS analysis demonstrated that Ento-A also restored SCFAs content in the intestinal tract. Finally, transcriptomic analysis revealed that Ento-A regulated the IL-17 signaling pathway. In summary, Ento-A regulates the diversity and abundance of intestinal flora in UC mice, enhancing the secretion of SCFAs, subsequently regulating the IL-17 signaling pathway, and ultimately repairing the intestinal mucosal barrier.

The mouse model of acute ulcerative colitis(UC) was established by skin sensitization via oxazolone(OXZ) combined with rectal enema. Successfully modeled mice were treated with Fuzi Lizhong Pills(FLP) for 7 consecutive days. The therapeutic effects were comprehensively evaluated. Untargeted metabolomics was employed to analyze fecal metabolic profiles, thereby elucidating the therapeutic mechanism of FLP for UC. The results showed that FLP significantly ameliorated the weight loss, diarrhea, and hematochezia in the mouse model of UC. Compared with the model group, the administration with FLP significantly reduced the DAI score, restored the colon length, repaired the pathological damage of the colon tissue, and reduced mucosal hyperemia, edema, and inflammatory cell infiltration. In terms of immune regulation, FLP significantly downregulated the expression levels of tumor necrosis factor(TNF)-α and interferon(IFN)-γ in the colon tissue and regulated spleen and thymus indices to restore the functional balance of immune organs. Untargeted metabolomics analysis of mouse feces indicated that FLP restored the levels of 126 differential metabolites, which were mainly involved in nicotinate and nicotinamide metabolism, propanoate metabolism, and phenylalanine metabolism pathways. In conclusion, FLP exhibits significant therapeutic effects on OXZ-induced UC in mice by regulating immune-inflammatory responses and correcting metabolic disorders.

Poria cocos polysaccharides alleviate dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis

Puerariae radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Kuiyangling is a traditional Chinese medicine formula usedfor the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis. A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg-1) and high-dose (10 g·kg-1), and mesalazine (50 mg·kg-1) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome. Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways. Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways.