Aug 2026· Molecular Nutrition & Food Research· Vol 70 16, pp.
e70585
· 0 citations· 26 references
Medicine
TL;DR
BRR shows significant promise in alleviating colitis-associated CRC through various mechanisms, including the modulation of gut microbiota, regulation of immune responses, and enhancement of intestinal barrier function.
Abstract
Colorectal cancer (CRC) linked to colitis is a major cause of cancer-related deaths, highlighting the need for effective treatment options. This study aimed to investigate the effects of berberine (BRR) on gut microbiota and the endocannabinoid system (ECS) in a mouse model of colitis-associated CRC, which was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Through a combination of animal experiments, microbial sequencing, and biochemical assays, we discovered that BRR significantly inhibited tumor development. This was demonstrated by a dose-dependent increase in body weight and a notable decrease in both the number and size of tumors. Histopathological examinations showed a reduction in aberrant crypt foci and inflammation. Additionally, BRR treatment led to lower levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, while increasing the levels of the anti-inflammatory cytokine IL-10, indicating a modulation of immune responses. Importantly, BRR altered gut microbial communities by promoting beneficial bacteria such as Akkermansia muciniphila, Bacteroides, Lachnoclostridium, Blautia, and Prevotellaceae_UCG-001, while reducing harmful species. We also observed improvements in intestinal barrier integrity, characterized by decreased permeability and lower levels of plasma lipopolysaccharides. Furthermore, BRR restored the expression of cannabinoid receptors CB2 and GPR55, suggesting that the ECS plays a role in mediating its effects. In summary, BRR shows significant promise in alleviating colitis-associated CRC through various mechanisms, including the modulation of gut microbiota, regulation of immune responses, and enhancement of intestinal barrier function. Future studies should aim to validate these findings clinically and further explore the efficacy of BRR in the prevention and treatment of CRC.
Colorectal cancer (CRC) is a multifactorial disease strongly influenced by genetic and environmental factors, as well as by immune and metabolic disorders such as obesity and gut dysbiosis. Recent evidence highlights the interplay between the endocannabinoidome (eCBome) and the gut microbiota as a central regulatory axis of intestinal homeostasis, metabolism, and immune responses. Although no studies have directly investigated this functional interaction in the CRC context, recent evidence suggests that dysfunction of the eCBome–microbiota axis, commonly observed in obesity, may influence colorectal tumorigenesis by impairing intestinal barrier integrity, increasing endotoxemia and immune dysregulation, altering microbial metabolite production, and activating NF-κB-mediated pro-tumorigenic signaling pathway. This is the first review to comprehensively integrate current evidence linking obesity-associated eCBome–microbiota dysfunction with CRC-related mechanisms and to propose potential pathways through which this interaction may influence CRC pathogenesis, providing a framework to guide future studies and support the development of novel preventive and therapeutic strategies for CRC.
Gabriela Ávila Alpino, P. G. Brasiel, Mariana M. Almeida et al.· Journal of physiology and bi...· 0 citations
Inflammatory Bowel Disease (IBD) is an inflammatory condition involving complex interactions among the intestinal epithelium, immune system, and gut microbiome. T-helper (Th) cells, particularly CD4+ effector cells, play a significant role in sustained inflammation and tissue damage. This study explores a novel compound, 7-Ketocholesterol (7-KC), an oxysterol, caged in methyl-β-Cyclodextrins (mβCD) for delivery to the cell membrane to disrupt lipid raft-based membrane order.
The approach targets CD4+ T cells and inflamed gut tissues in Dextran Sulfate Sodium (DSS)-induced acute IBD mouse model. Disease severity in the 7-KC-treated test and control mice was monitored daily using weight loss, water intake, and stool hemoccult scoring. At the experimental endpoint, mice were euthanized to measure colon length. The proximal, medial, and distal parts of the colon were prepared for histological and immunohistochemical analyses.
The DSS-only group (disease control) developed severe colitis, confirmed by a significant mean weight loss of 13.92% ± 3.58%, substantial colon shortening (6.97 ± 0.46 cm), and high stool hemoccult scores (2.75±0.46). The 7-KC treatment showed disease mitigation in weight loss, colon length, and stool hemoccult scores.
These findings show that the treatment with 7-KC alleviated the clinical symptoms in the acute DSS-induced IBD mouse model, suggesting therapeutic benefits of 7-KC. We will present these data along with images of colon histology and assessment of inflammation in the colon.
Villanova University
Translational and Interventional Immunology (TI)
A. Bamezai, Emma Behrman· Journal of Immunology· 0 citations
ETHNOPHARMACOLOGICAL RELEVANCE
Coicis Semen is a classic example of a resource used both as food and medicine. In traditional Chinese medicine, it is known for several functions: promoting diuresis, resolving dampness, strengthening the spleen, stopping diarrhea, draining pus, and removing toxins. For a long time, it has been widely used to relieve symptoms of gastrointestinal disorders. In particular, Coixol shows strong biological activity when it comes to regulating intestinal inflammation. However, its specific therapeutic potential and underlying mechanisms in ulcerative colitis (UC) have not been fully elucidated.
AIM OF THE STUDY
This research aimed to define the therapeutic potential of Coixol in ulcerative colitis and clarify its regulatory influence on the Axin1-mediated Wnt signaling axis and the subsequent activation of group 3 innate lymphoid cells (ILC3).
MATERIALS AND METHODS
We established a colitis model in mice using dextran sulfate sodium and utilized LPS-stimulated macrophages for in vitro assays. Therapeutic outcomes were measured through disease activity scores, tissue histology, and epithelial barrier assessment. We integrated bulk RNA sequencing and Olink proteomics to pinpoint core regulatory pathways. We then validated Axin1 as the direct molecular target of the drug using molecular docking, surface plasmon resonance, and cellular thermal shift assay. Mechanistic insights were further substantiated by Western blot, flow cytometry, and a pharmacological rescue experiment using a Wnt signaling activator. Finally, the functional necessity of this axis was confirmed via IL-22 neutralization assays, demonstrating the regulatory link between Axin1 and the observed phenotypic changes.
RESULTS
Coixol intervention significantly lowered inflammatory markers and promoted the restoration of the intestinal wall. Coixol modulated macrophage polarization and increased Axin1 protein levels to trigger the degradation of β-catenin. Furthermore, flow cytometry demonstrated that Coixol expanded the colonic ILC3 population, a process essential for driving IL-22-dependent mucosal healing. This protective effect was reversed by an IL-22-neutralizing antibody.
CONCLUSION
Coixol effectively mitigates experimental colitis by targeting the Axin1 and Wnt axis to promote ILC3 expansion and subsequent IL-22 production. These results provide a modern scientific foundation for the traditional medicinal use of Coicis Semen and highlight the Axin1 and ILC3 module as a viable target for treating UC.
Jia-li Ma, Qianqian Yin, Yi-jing Zhou et al.· Journal of Ethnopharmacology· 0 citations
Background/Aims
The treatment of colorectal cancer (CRC) remains a challenge in clinical research. Zeaxanthin (ZEA) has demonstrated substantial anti-inflammatory and anticancer effects. However, its preventive effects and underlying mechanisms in CRC remain elusive. Therefore, this study investigated the preventive effects and 10 molecular mechanisms of ZEA in CRC.
Materials and Methods
The effects of ZEA on tumor formation, inflammatory responses, and cell proliferation were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse model of CRC. Furthermore, the anti-inflammatory and antiproliferative mechanisms of ZEA were evaluated in vitro using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and CRC cell lines (HCT116 and SW620).
Results
Treatment with 50 mg/kg ZEA significantly inhibited AOM/DSS-induced CRC progression. Furthermore, treatment with ZEA reduced tumor formation in the colonic lining, increased body weight, enhanced colorectal length, improved overall survival rate, and attenuated pathological changes in mice. Moreover, ZEA significantly reduced proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and Ki-67 expression levels. Mechanistically, ZEA mitigated inflammation in LPS-stimulated RAW264.7 macrophages by suppressing the nucleotide-binding oligomerization domain-containing protein 1 (NOD1)/receptor-interacting protein 2 kinase (RIP2)/ nuclear factor-κB (NF-κB) signaling pathway. In addition, it suppressed proliferation of HCT116 and SW620 cells by inhibiting the signaling pathway of PI3K/AKT/MYC.
Conclusion
ZEA exerted significant anti-CRC effects, including anti-inflammatory and antiproliferative actions through multitarget mechanisms, such as modulation of the NOD1/RIP2/NF-κB and PI3K/AKT/MYC signaling pathways. These findings suggest that ZEA is a promising natural chemopreventive agent for the prevention and treatment of CRC.
Mengxiang Yang, Yuejun Han, Ting Jin et al.· The Turkish Journal of Gastr...· 0 citations
BACKGROUND
Ulcerative colitis (UC) is a type of inflammatory bowel disease. Macrophage polarization is crucial in the development of UC. Oxypalmatine (OPAL) is an isoquinoline alkaloid that can be isolated from various plant, including Phellodendron amurense and Sinomenium acutum. It is also an oxidative metabolite derived from the hepatic biotransformation of palmatine (PAL), which is one of the active constituents of Coptis chinensis that demonstrates anti-inflammatory and antioxidant properties.
PURPOSE
This study aimed to explore the anti-inflammatory properties of OPAL and the mechanisms involved.
METHODS
Efficacy of OPAL and its impact on macrophage polarization were assessed in a dextran sodium sulfate (DSS)-induced mouse model of colitis. Necessity of macrophage in the alleviation by OPAL was confirmed with a macrophage-depletion model. Transcriptomics analysis was performed on the colon to identify the corresponding signaling pathways. In an in vitro model of THP-1-derived macrophage, the effect of OPAL was assessed in terms of cell energy metabolism, cytokines production, and epithelium damage. Target of OPAL was explored by limited proteolysis-mass spectrometry (LiP-MS) analysis and siRNA-mediated knockdown.
RESULTS
OPAL significantly ameliorated DSS-induced colitis by reducing colon shortening, weight loss and intestinal barrier damage, which relied on the inhibition on M1 polarization as confirmed by flowcytometry and macrophage-depletion. In vitro, OPAL suppressed the inflammatory response in THP-1-derived macrophages, and reprogrammed the energy metabolism profile by reducing the glycolysis and enhancing basal respiration and maximal respiration. Mechanistically, OPAL inhibited M1 polarization via suppressing the JAK-STAT signaling pathway, which mainly relied on binding to RAB8A protein to suppress STAT1 phosphorylation and the consequent HK2 expression.
CONCLUSION
OPAL ameliorated UC by suppressing M1 macrophage polarization via the RAB8A/STAT1 axis, highlighting a promising treatment strategy for UC management.
Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that dihydroquercetin (DHQ) exerts anti-oxidative, anti-inflammatory and cell-protective properties as a natural occurring flavonoid compound, but its effects on IBD remain unclear. In this study, the mice were administered DHQ or fecal transplantation (FMT) followed by DSS administration, after which colitis symptoms, inflammation levels and intestinal barrier function were evaluated. Transcriptome and metabolome analysis of colon were conducted to explore the pathogenesis of colitis. Lastly, we analyzed the potential molecular mechanisms of DHQ in treating colitis by integrating network pharmacology, molecular docking technology and molecular biology experiments. DHQ or FMT protected mice from DSS-induced colitis, suppressed the inflammation and restored the weakened epithelial barrier. Transcriptome and metabolome analysis indicated that decreasing phospholipid level generated by phospholipase D signaling pathway (AVPR1A/PLCB1/PLA2) activation in colon mediated the occurrence of DSS-induced colitis. DHQ or FMT reversed the colitis of mice by regulating PPARγ/AVPR1A/PLCB1/PLA2 pathway. This research firstly discovers that increased phospholipid breakdown caused by PPARγ/AVPR1A/PLCB1/PLA2 leads to the disruption of the intestinal barrier and the occurrence of DSS-induced colitis. This research also provides new perspectives for understanding the pathogenesis of colitis and the protective effects of DHQ.
Junxi Pan, Jing Yang, Liu Tang et al.· Chemico-Biological Interacti...· 0 citations
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