Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis

Yi-Rong Li; Der-Yuan Chen; Ching-Liang Chu; Shiming Li; Yu-Kuo Chen; Chao-Ling Wu; Chi-Chen Lin

doi:10.1016/j.jnutbio.2015.07.016

Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis

J Nutr Biochem. 2015 Dec;26(12):1467-78. doi: 10.1016/j.jnutbio.2015.07.016. Epub 2015 Aug 8.

Authors

Yi-Rong Li¹, Der-Yuan Chen², Ching-Liang Chu³, Shiming Li⁴, Yu-Kuo Chen⁵, Chao-Ling Wu⁶, Chi-Chen Lin⁷

Affiliations

¹ Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan.
² Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan.
³ Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan.
⁴ Department of Food Science, Rutgers University, New Brunswick, NJ, USA; Colleage of Chemistry and Chemical Engineering, Huanggang Normal University, Hubei, China.
⁵ Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.
⁶ Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan.
⁷ Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan. Electronic address: lincc@dragon.nchu.edu.tw.

PMID: 26350255
DOI: 10.1016/j.jnutbio.2015.07.016

Abstract

The aim of this study was to investigate the effect of naringenin (5,7,4'-trihydroxyflavanone), a citrus flavonoid, on dendritic cell (DC) maturation, as well as its potential as a therapeutic agent in a murine model of collagen-induced arthritis (CIA). Naringenin effectively inhibited lipopolysaccharide (LPS)-induced DC maturation as shown by reductions in the production of proinflammatory cytokines/chemokines, the expression of costimulatory molecules and the Ag-specific T cell priming ability of DCs when given at noncytotoxic doses. In addition, the decrease of LPS-induced MAPK and NF-κB signaling activation may contribute to the inhibitory activity of naringenin. In mice with CIA, the oral administration of naringenin ameliorated the severity of arthritis, reduced the levels of anticollagen Type II (CII) IgG and limited the proliferation of T cells, observed as a lower frequency of Th1 and Th17 cells in the spleen after restimulation with CII. In conclusion, this study shows for the first time that naringenin can manipulate the immunostimulatory properties of DCs and thus represents a potential therapeutic for the treatment of rheumatoid arthritis in humans.

Keywords: Collagen-induced arthritis; Dendritic cells; Flavonoid; Maturation; Naringenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Arthritis, Experimental / metabolism*
Arthritis, Rheumatoid / metabolism
CD4-Positive T-Lymphocytes / cytology
Cell Proliferation
Cell Survival
Collagen / adverse effects*
Dendritic Cells / cytology*
Disease Models, Animal
Dose-Response Relationship, Drug
Flavanones / chemistry*
Immunoglobulin G / blood
Inflammation
Ligands
Lipopolysaccharides / chemistry
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
NF-kappa B / metabolism
Signal Transduction
Spleen / metabolism
Th1 Cells / cytology
Th17 Cells / cytology

Substances

Flavanones
Immunoglobulin G
Ligands
Lipopolysaccharides
NF-kappa B
Collagen
naringenin