Ulcerative colitis (UC), a chronic and challenging condition, necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications. Traditional Chinese medicine (TCM), known for its multi-stage and multi-targeted approach, has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment. Panax ginseng (P. ginseng), a commonly used remedy for UC in TCM, exemplifies this potential, although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated, highlighting the need for further research to unlock its full potential as a treatment option.

To investigate the key constituents and biological pathways through which P. ginseng exerts therapeutic effects on UC.

Network pharmacology investigated the UC-alleviating mechanism of P. ginseng, including "active ingredient-target-disease" network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Panaxadiol (PD; active ingredient of P. ginseng) was tested in a mouse model of 3% dextran sulfate sodium-induced UC, with assessments of body weight, Disease Activity Index scores, and colon length. Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining, immunohistochemistry, real time-quantitative PCR, and western blotting.

By integrating and analyzing the targets of P. ginseng and UC, 15 critical hub genes were discovered. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling. Among the 10 main active ingredients identified as potentially effective, PD was most abundant and was validated in vivo to mitigate weight loss, reduce Disease Activity Index scores, and prevent colon shortening. PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators. In addition, PD increased expression of mucin and tight junction proteins. Ultimately, PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK, while increasing phosphorylation of AMPK and expression of NRF2 and NQO1.

PD alleviates colitis and aids intestinal barrier repair, partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways. These findings also suggest new research methods for treatment of UC with TCM.

Ulcerative colitis (UC) is a chronic inflammatory bowel condition that significantly impairs patient quality of life and remains incurable. Effective dietary management is crucial for both prevention and treatment. This study investigates the effects and mechanisms of Eurotium cristatum-fermented black tea (FBT) in a dextran sulfate sodium (DSS)-induced UC mouse model using transcriptome sequencing, immunofluorescence, and flow cytometry. Our results demonstrate that FBT significantly protects intestinal integrity by suppressing NF-κB-dependent inflammatory genes through the activation of peroxisome proliferator-activated receptor gamma (PPARγ) and modulation of the NF-κB signaling pathway. FBT enhances intestinal barrier integrity by limiting microbial penetration and metabolite translocation into systemic circulation, thereby reducing systemic inflammation risk. Additionally, FBT promotes intestinal mucosa repair and maintains microecological homeostasis by regulating intestinal flora and enhancing the biosynthesis of short-chain fatty acids and amino acids. These findings suggest that FBT has promising prophylactic potential for preventing and alleviating UC by modulating multiple biological pathways, including reducing inflammation, mitigating oxidative stress, and strengthening intestinal barrier integrity. This study lays the groundwork for future research on dietary interventions for UC prevention and management.

Numerous studies have shown that exposure to micro- or nano-plastics led to the cell viability and function of macrophages in the intestine tissue might be one possible mechanism. This study investigated the cytotoxicity and pro-inflammatory effect of 80 nm polystyrene-nano-plastic (PS-NP) and 3 µm PS-micro-plastic (PS-MP) on mouse macrophages RAW264.7 cells. Our results showed that exposure to PS-NP or PS-MP induced apoptosis of cells at 5 or 10 μg/mL, respectively. Besides, PS-NP enhanced the secretion of inflammatory cytokines (Tumor necrosis factor-α, Interleukin-6 and Interleukin-10) with the lowest effective concentration (LOEC) of 1, 0.01, and 0.01 μg/mL, respectively. PS-MP enhanced secretion of TNF-α and IL-10 with the LOEC of 1 and 0.01 μg/mL, respectively. We further studied the possible mechanisms of the effects of PS-NP or PS-MP on RAW264.7 cells. We found they might cause cytotoxicity and inflammatory effects by producing reactive oxygen species and nitric oxide in the cells. Accordingly, our results demonstrated that PS-NP and PS-MP had cytotoxicity and pro-inflammatory effect on macrophages, which might further lead to intestinal inflammation. Moreover, we revealed that the PS-NP had more potent adverse impacts on macrophages than PS-MP.

Inflammatory bowel disease (IBD) is a form of nonspecific chronic intestinal inflammation associated with gut microbiome dysbiosis. Modulating the composition of the intestinal flora may be a viable means of alleviating such inflammatory pathology. Bacteroides thetaiotaomicron (B. thetaiotaomicron) is a symbiotic intestinal microbe that has been associated with IBD, although the mechanistic basis for this association remains to be clarified. In this present study, we determined that B. thetaiotaomicron can alleviate colonic inflammation through mechanisms associated with the modulation of tryptophan metabolism and T cell subsets within inflamed intestinal tissues. Specifically, we found that B. thetaiotaomicron promotes the preferential differentiation of anti-inflammatory Treg/Th2 cells while suppressing the relative differentiation of pro-inflammatory Th1/Th17 cells, thereby decreasing inflammation within the colon. At a molecular level, B. thetaiotaomicron treatment was linked to altered CpG methylation within the Foxp3 promoter that was associated with enhanced Treg cell functionality. In a murine dextran sulfate sodium (DSS) colitis model system, B. thetaiotaomicron increased the levels of the aryl hydrocarbon receptor (AHR) ligands indole metabolites-indole acetic acid (IAA) and indole propionic acid (IPA), thereby increasing AHR activation that is related to changes of transcription factor expression profiles within T cells. In summary, our data suggest that B. thetaiotaomicron can activate AHR and modulate CD4⁺ T cell differentiation profiles in a murine DSS colitis model system, suggesting that this bacterium may be of therapeutic relevance for the treatment of IBD.

The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis.

Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis.

Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins.

It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.