Improved colonic inflammation by nervonic acid via inhibition of NF-κB signaling pathway of DSS-induced colitis mice
DATE:
2023-04
UNIVERSAL IDENTIFIER: http://hdl.handle.net/11093/4930
EDITED VERSION: https://linkinghub.elsevier.com/retrieve/pii/S0944711323000624
DOCUMENT TYPE: article
ABSTRACT
Background: Nervonic acid (C24:1Δ15, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty
acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory
properties. 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, we
wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse
colitis 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 therapeutic
effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and
eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were
used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal
tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in
the 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 of
key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the
mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal
pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection
against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine
and purine metabolism.
Conclusion: These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the
NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or
treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food
ingredient for preventing and treating inflammatory bowel disease (IBD).