Galangin modulation of the IL-23/IL-17 axis mitigates ulcerative colitis through attenuation of oxidative/nitrative stress and inflammation

Abstract

The pathophysiology of Ulcerative Colitis (UC) involves the imbalance of pro-inflammatory cytokines, including interleukin (IL)-23 and IL-17, which play a crucial role in the development and progression of UC. Galangin (Gal), a natural flavonoid compound, has been shown to possess anti-inflammatory, antioxidant, and immunomodulatory properties. Therefore, this study aimed to investigate the potential therapeutic effects of Gal on a mouse model of dextran sulfate sodium (DSS)-induced UC by targeting the IL-23/IL-17 axis. Forty male C57BL/6 mice were randomly divided into four groups and assessed clinical and histopathological features. The colon tissues were collected for protein analysis using Western Blotting. Also, ELISA and colorimetric analysis were used to measure cytokines and oxidative/nitrative stress markers, respectively. The expressions of iNOS and COX-2 were measured by real-time quantitative PCR (RT-qPCR). We found that Gal treatment significantly attenuated the severity of UC, as evidenced by the improvement of clinical symptoms, histopathology, and reduced levels of proinflammatory cytokines, including IL-23 (fold change: 0.64; p < 0.05) and IL-17 (fold change: 0.56; p < 0.05). Moreover, Gal treatment inhibited the activation of the NF-κB pathway. Furthermore, we demonstrated that Gal treatment significantly suppressed oxidative/nitrative stress by reducing the expression levels of iNOS (fold change: 0.46; p < 0.01) and COX-2 (fold change: 0.52; p < 0.01), the two key enzymes involved in the production of reactive oxygen/nitrogen species (ROS/RNS), and increasing the activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase. Our findings suggested that Gal targeting the IL-23/IL-17 axis improves UC by suppressing oxidative/nitrative stress and inflammation.