2. Academic Validation
  3. Improved colonic inflammation by nervonic acid via inhibition of NF-κB signaling pathway of DSS-induced colitis mice

Improved colonic inflammation by nervonic acid via inhibition of NF-κB signaling pathway of DSS-induced colitis mice

  • Phytomedicine. 2023 Apr:112:154702. doi: 10.1016/j.phymed.2023.154702.
Sheng-Nan Yuan 1,  Mu-Xuan Wang 1,  Jin-Long Han 1,  Cai-Yun Feng 1,  Meng Wang 2,  Min Wang 3,  Jin-Yue Sun 4,  Ning-Yang Li 5,  Jesus Simal-Gandara 6,  Chao Liu 7
Affiliations

Affiliations

  • 1 Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China.
  • 2 Shanxi Functional Food Engineering Center Co. Ltd, Xian 710000, China.
  • 3 College of Food Science and Engineering, Northwest A&F University, Xianyang 712100, China.
  • 4 Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China; Shandong Huatai Nutrition and Health Industry Technology Research Institute Co. Ltd, Jinan 250100, China. Electronic address: moon_s731@hotmail.com.
  • 5 Key Laboratory of Food Processing Technology and Quality Control in Shandong Province, College of Food Science and Engineering, Shandong Agricultural University, Taian, China. Electronic address: nigyangli@126.com.
  • 6 Universidade de Vigo, Nutrition and Bromatology Group, Analytical Chemistry and Food Science Department, Faculty of Science, E-32004 Ourense, Spain. Electronic address: jsimal@uvigo.es.
  • 7 Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China; Shandong Huatai Nutrition and Health Industry Technology Research Institute Co. Ltd, Jinan 250100, China. Electronic address: liuchao555@126.com.
PMID: 36764096 DOI: 10.1016/j.phymed.2023.154702
Abstract

Background: Nervonic acid (C24:1∆15, 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).

Keywords

Inflammatory factors; Macrophages; NF-κB signaling pathway; Nervonic acid; Ulcerative colitis.

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