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Intestinal anti‐inflammatory activity of luteolin: Role of the aglycone in NF‐κB inactivation in macrophages co‐cultured with intestinal epithelial cells
Author(s) -
Nishitani Yosuke,
Yamamoto Koji,
Yoshida Masaru,
Azuma Takeshi,
Kanazawa Kazuki,
Hashimoto Takashi,
Mizuno Masashi
Publication year - 2013
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1091
Subject(s) - luteolin , proinflammatory cytokine , tumor necrosis factor alpha , microbiology and biotechnology , lipopolysaccharide , chemistry , inflammation , caco 2 , aglycone , interleukin , downregulation and upregulation , cytokine , biology , in vitro , biochemistry , immunology , flavonoid , organic chemistry , glycoside , gene , antioxidant
The flavonoid luteolin is reported to exert anti‐inflammatory properties. In this study, we investigated whether luteolin inhibits gut inflammation, using in vivo and in vitro inflammation models. In a dextran sulfate sodium (DSS)‐induced colitis mouse model, luteolin (20 and 50 mg/kg) significantly ameliorated shortening of colon length and histological score. Immunohistochemical analysis showed that luteolin also significantly inhibited infiltration of macrophages and interferon (IFN)‐γ‐producing CD4 + T cells into the colonic mucosa. Treatment with luteolin also improved IFN‐γ mRNA expression in the colon. At the cellular level, a co‐culture consisting of intestinal epithelial Caco‐2 and macrophage RAW264.7 cells, stimulated with lipopolysaccharide, the addition of luteolin (100 μM) suppressed interleukin (IL)‐8 mRNA expression in Caco‐2 cells without epithelial monolayer disruption. Expression of tumor necrosis factor (TNF)‐α protein and proinflammatory cytokines mRNA (TNF‐α, IL‐6, and IL‐1β) in RAW264.7 cells were also suppressed. HPLC analysis and subsequent cellular assay revealed that aglycone of luteolin was present in the basolateral supernatant of this system at a sufficient concentration to suppress TNF‐α production and nuclear factor (NF)‐κB activation of RAW264.7 cells. These results suggest that the luteolin aglycones released from the Caco‐2 epithelium inhibits NF‐κB nuclear translocation in RAW264.7 cells, followed by reduction of TNF‐α mRNA expression, which results in downregulation of IL‐8 mRNA expression in Caco‐2 cells. The mechanism by which aglycone inhibits inflammation is important for understanding the roles of luteolin in diet. © 2013 BioFactors 39(5):522–533, 2013