Protective Effect and Mechanisms of Eckol on Chronic Ulcerative Colitis Induced by Dextran Sulfate Sodium in Mice

Mar Drugs. 2023 Jun 25;21(7):376. doi: 10.3390/md21070376.

Abstract

The use of functional foods and their bioactive components is receiving increasing attention as a complementary and alternative therapy for chronic ulcerative colitis (UC). This study explored the protective effect and mechanisms of Eckol, a seaweed-derived bioactive phlorotannin, on the dextran sodium sulfate (DSS)-induced chronic UC in mice. Eckol (0.5-1.0 mg/kg) reduced DSS-enhanced disease activity indexes, and alleviated the shortening of colon length and colonic tissue damage in chronic UC mice. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly decreased, and the level of anti-inflammatory IL-10 was enhanced in the serum and colonic tissues collected from Eckol-treated mice compared with the DSS controls. Eckol administration significantly reduced the number of apoptotic cells and the expression of cleaved Caspase-3, and increased the B-cell lymphoma-2 (Bcl-2)/B-cell lymphoma-2- associated X (Bax) ratio in DSS-challenged colons. There were more cluster of differentiation (CD)11c+ dendritic cells and CD8+ T cells, and less CD4+ T cells infiltrated to inflamed colonic tissues in the Eckol-treated groups. Expression of colonic Toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) p65, phosphorylated-signal transducer and activator of transcription (pSTAT)3 was significantly down-regulated by Eckol compared with the DSS-challenged group. In conclusion, our data suggest that Eckol appeared to be a potential functional food ingredient for protection against chronic UC. The anti-colitis mechanisms of Eckol might be attributed to the down-regulation of the TLR4/NF-κB/STAT3 pathway, inhibition of inflammation and apoptosis, as well as its immunoregulatory activity.

Keywords: Eckol; TLR4 pathway; apoptosis; chronic ulcerative colitis; immunoregulation; inflammation.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / metabolism
  • Colon / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Dextran Sulfate
  • Toll-Like Receptor 4
  • eckol
  • Tumor Necrosis Factor-alpha
  • Proto-Oncogene Proteins c-bcl-2