C-glycosyl flavonoid orientin improves chemically induced inflammatory bowel disease in mice

• Orientin attenuated DSS-induced colitis in mice.
• Orientin decreased the production of inflammatory mediators.
• Orientin down-regulated the DSS-induced expression of TLR4.
• Orientin inhibited the DSS-induced activation of NF-κB signalling.
• Orientin inhibited the DSS-induced activation of MAPK signalling molecules.

Orientin is a C-glycosyl flavonoid found abundantly in some fruits and herbs. The present study demonstrated that orientin (50 and 100 mg/kg/d) alleviated the severity of dextran sulphate sodium (DSS)-induced colitis in mice by decreasing the activity of myeloperoxidase (MPO) and the production of cytokines. Concomitant up-regulation of toll-like receptor (TLR)-4 after DSS exposure was associated with an increase in the activation of myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase (IRAK)-1, nuclear factor kappa B (NF-kB) p65, as well as the mitogen-activated protein kinase (MAPK) molecules (ERK1/2, JNK and p38), and this upregulation was reversed by orientin administration. Moreover, orientin inhibited the nuclear translocation of NF-kB p65, the activity of NF-kB-luciferase, and the expression of NF-kB target genes. These findings suggest that orientin attenuates experimental inflammatory bowel disease (IBD) via suppression of TLR4 and inactivation of NF-kB and MAPK pathways.