Protective effect of 17S-epoxy-docosapentaenoic acid against dextran sulfate sodium induced ulcerative colitis in BALB/c mice = 궤양성 대장염 마우스모델에 대한 신규 DHA 유도체의 염증 제어 및 조직재생 효능

Abstract

Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study demonstrated the protective effect of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA), which had been previously synthesized, on a dextran sulfate sodium (DSS)-induced BALB/c mouse model of UC. UC was induced with 4% DSS drinking water for 7 days. Initially, the anti-inflammatory effect of diHEP-DPA was confirmed by demonstrating that lipopolysaccharide-stimulated THP1 cells treated with diHEP-DPA decreased IL-6, TNF-α and nitrite levels by fluorescence-activated cell sorting (FACS) and Griess reagent kit. The results indicated that the administration of diHEP-DPA at 20 μg/kg significantly reduced the severity of colitis, as determined by hematoxylin and eosin staining. The levels of TNF-α, IL-6 and IL-1β in the colon tissue and serum were significantly reduced in the diHEP-DPA + DSS-treated group compared with in the control group, as determined by FACS and ELISA kit. It was also observed that diHEP-DPA decreased myeloperoxidase (MPO) and nitrite levels in the colon tissues of diHEP-DPA + DSS-treated mice, as indicated using commercial MPO and nitric oxide kits. The diHEP-DPA+DSS-treated mice also exhibited decreased expression levels of phosporylated (p)-inhibitor κB protein, p-p65 and inducible nitric oxide synthase in the colon tissue by inhibiting inflammation, which were measured by reverse transcription-quantitative PCR and weatern blot analysis. Overall, the present study demonstrated the protective effect of diHEP-DPA against a severe colitis condition in vivo.