docosapentaenoic-acid and Colitis

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

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Acids, Unsaturated; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; NF-kappa B; Nitrites; Tumor Necrosis Factor-alpha

Enzymatically oxygenated lipid products derived from omega-3 and omega-6 fatty acids play an important role in inflammation dampening. This study examined the anti-inflammatory effects of n-6 docosapentaenoic acid-derived (17S)-hydroxy-docosapentaenoic acid (17-HDPAn-6) and (10,17S)-dihydroxy-docosapentaenoic acid (10,17-HDPAn-6) as well as n-3 docosahexaenoic acid-derived 17(R/S)-hydroxy-docosahexaenoic acid (17-HDHA).. The effects of 17-HDPAn-6, 10,17-HDPAn-6 or 17-HDHA on activity and M1/M2 polarization of murine macrophage cell line RAW 264.7 were examined by phagocytosis assay and real-time PCR. To assess anti-inflammatory effects in vivo, dextran sodium sulfate (DSS) colitis was induced in mice treated with 17-HDPAn-6, 10,17-HDPAn-6, 17-HDHA or NaCl.. Our results show that 17-HDPAn-6, 10,17-HDPAn-6 and 17-HDHA increase phagocytosis in macrophages in vitro and promote polarization towards the anti-inflammatory M2 phenotype with decreased gene expression of TNF-α and inducible Nitric oxide synthase and increased expression of the chemokine IL-1 receptor antagonist and the Scavenger receptor Type A. Intraperitoneal treatment with 17-HDPAn-6, 10,17-HDPAn-6, or 17-HDHA alleviated DSS-colitis and significantly improved body weight loss, colon epithelial damage, and macrophage infiltration.. These results suggest that DPAn-6-derived 17-HDPAn-6 and 10,17-HDPAn-6 as well as the DHA-derived 17-HDHA have inflammation-dampening and resolution-promoting effects that could be used to treat inflammatory conditions such as inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis; Disease Models, Animal; Docosahexaenoic Acids; Fatty Acids, Unsaturated; Macrophages; Mice; Phagocytosis