Chronic gut inflammation disposes to an increased risk of colitis-associated cancer. Chemoprevention is an attractive complementary strategy. We aimed to evaluate the chemopreventive effects of M10, a novel derivative of Myricetin, in the murine azoxymethane/dextran sodium sulfate model. Oral administration of M10 at 50-100 mg/kg once a day for consecutive 12 weeks significantly prevented ulcerative colitis (UC) and colorectal tumor. Pathological analysis of intestines showed that M10 reduced the degree of chronic inflammation and prevented the progression of colorectal tumorigenesis. Flow cytometry analysis of the immunocytes isolated from intraepithelial and lamina propria showed that M10 prevented the infiltration of myeloid-derived suppressor cells and increased CD8+T and CD4+T cells in colorectal tissues. Enzyme-linked immunosorbent analysis revealed the reduction of pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor/macrophage colony-stimulating factor, IL-6 and TNF-α in colonic mucosa. Western blot assay also showed M10 prevention of the NF-κB/IL-6/STAT3 pathways and the biomarkers of inflammation and colorectal tumorigenesis. Electron microscopy analysis revealed that M10 prevent robust endoplasmic reticulum (ER) stress-induced autophagy in inflamed colonic mucosal cells. In conclusion, oral administration of Myricetin derivative M10 exerts chemoprevention of UC and colorectal tumor in mice. The mechanism of chemoprevention is associated with the reduction of biomarkers of chronic inflammation and proliferation through attenuating robust ER stress in inflamed colonic mucosal cells. M10 exerts chemoprevention activity without evidence of toxicity in mice. These results justify further evaluation of M10 in clinical trials. M10 could develop a promising regimen in the chemoprevention of colitis and colorectal cancer.
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http://dx.doi.org/10.1093/carcin/bgy057 | DOI Listing |
J Ethnopharmacol
January 2025
State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, 519000, China. Electronic address:
Ethnopharmacological Relevance: In traditional Chinese medicine, the radices of Glycyrrhiza uralensis Fisch, known as liquorice, have been used for relieving cough, alleviating pain and harmonizing the actions of all medicinals in a formula. Glycyrrhizic acid (GA), a natural compound derived from licorice, exhibits notable anti-inflammatory properties.
Aim: Neutrophil extracellular trap (NET) generated by peptidylarginine deiminase 4 (PAD4) has been implicated in the progression of colitis to colitis-associated colorectal cancer (CAC).
Am J Gastroenterol
December 2024
Gastroenterology Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
This study investigates whether subclinical inflammation in asymptomatic inflammatory bowel disease (IBD) patients leads to increased medication use. In a multicenter, retrospective analysis of patients diagnosed with incidental ulcerative colitis or Crohn's disease during colorectal cancer screening (2010-2021), medication use was compared with symptomatic patients and healthy non-IBD controls. Asymptomatic patients showed a higher use of cardiovascular, antiparasitic, musculoskeletal, respiratory, and sensory organ medications up to five years before diagnosis.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Gastroenterology and.
Although biologics have been revolutionizing the treatment of inflammatory bowel diseases (IBD) over the past decade, a significant number of patients still fail to benefit from these drugs. Overcoming the nonresponse to biologics is one of the top challenges in IBD treatment. In this study, we revealed that hyaluronan (HA), an extracellular matrix (ECM) component in the gut, is associated with nonresponsiveness to infliximab and vedolizumab therapy in patients with IBD.
View Article and Find Full Text PDFBMC Genomics
January 2025
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
The E. coli strains harboring the polyketide synthase (pks) island encode the genotoxin colibactin, a secondary metabolite reported to have severe implications for human health and for the progression of colorectal cancer. The present study involves whole-genome-wide comparison and phylogenetic analysis of pks harboring E.
View Article and Find Full Text PDFJ Genet Genomics
January 2025
Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. Electronic address:
Colitis-associated colorectal cancer (CAC), a serious complication of ulcerative colitis (UC), is associated with a poor prognosis. The vitamin D receptor (VDR) is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation. This study demonstrates a significant reduction in mA-related genes, particularly methyltransferase like 14 (METTL14), in UC and CAC patients and identifies an association between METTL14 and VDR.
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