Effect of the Flavonoid Luteolin for Dextran Sodium Sulfate-induced Colitis in NF-kappa BEGFP Transgenic Mice

Jang, Byung Ik

Abstract

BACKGROUND: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-kappa B and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. MATERILAS AND METHODS: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappa B cis-elements. C57BL/6 NF-kappa BEGFP mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-kappa B activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis.
RESULTS
A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-kappa B activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells.
CONCLUSIONS
These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.