Calycosin attenuates dextran sulfate sodium (DSS)-induced experimental colitis

Objective(s): Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immunity. It is an incurable disease that affects millions of people worldwide. Developing new strategies for the treatment of colitis has been a major challenge. Here, we report the effect of calycosin, a plantderived flavonoid, in successfully managing colitis in murine model. Material and Methods: In vivo model of colitis was induced using 2.5% (w/v) dextran sodium sulfate (DSS, 36,000 to 50,000 Mw). Body weight and disease activity index (DAI) were evaluated every day. Hematoxylin-Eosin (H&E) staining was used to estimate the effect of calycosin on DSS-induced colon damage. The levels of proinflammatory genes and mRNA expression were determined using real-time PCR, whereas the proinflammatory cytokines were assessed with ELISA. The content of other parameters including myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) were also evaluated. Western blot assay was further used to determine the effect of calycosin on both NF-kappa B and mitogen activated protein kinases (MAPK) pathways. Results: The results showed that calycosin prevented weight loss and shortening of the colon length, maintained an intact mucosa, increased GSH and SOD activities, and decreased MDA levels. The drug also significantly inhibited proinflammatory cytokine mRNA expression and decreased MPO activity. Additionally, it remarkably inhibited NF-kappa B pathway and c-Jun N-terminal kinase (JNK) phosphorylation with no effect on p38 and extracellular signal-regulated kinase (ERK1/2) phosphorylation levels in colon tissue. Conclusion: These findings revealed that calycosin successfully ameliorated the effect of DSS-induced colitis in mice, which could be associated with NF-kappa B and JNK pathway modulations.