RT Journal Article
T1 Improved colonic inflammation by nervonic acid via inhibition of NF-κB signaling pathway of DSS-induced colitis mice
A1 Yuan, Sheng-Nan
A1 Wang, Mu-xuan
A1 Han, Jin-Long
A1 Feng, Cai-Yun
A1 Wang, Meng
A1 Wang, Min
A1 Sun, Jin-Yue
A1 Li, Ning-yang
A1 Simal Gándara, Jesús
A1 Liu, Chao
K1 3205.03 Gastroenterología
K1 3207.10 Inmunopatología
K1 2302.11 Acidos grasos
AB Background: Nervonic acid (C24:1Δ15, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fattyacid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatoryproperties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine.The influences of NA on UC are largely unknown.Purpose: The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, wewanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mousecolitis model.Methods: To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide(LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β(IL-1β), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeuticeffects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin andeosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS wereused to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinaltight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved inthe nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR.Results: In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation ofkey signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from themouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signalpathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protectionagainst UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidineand purine metabolism.Conclusion: These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress theNF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention ortreatment therapy for UC. This work for the first time indicated that NA might be a potential functional foodingredient for preventing and treating inflammatory bowel disease (IBD).
PB Phytomedicine
SN 09447113
YR 2023
FD 2023-04
LK http://hdl.handle.net/11093/4930
UL http://hdl.handle.net/11093/4930
LA eng
NO Phytomedicine, 112, 154702 (2023)
NO National Key Research and Development, China | Ref. 2021YFE0109200
DS Investigo
RD 13-oct-2024