Shikonin inhibits colitis-associated colorectal dysplasias in a mouse model of azoxymethane/dextran sulfate sodium colitis

Shikonin (Shk) inhibits the development of colorectal dysplasia and the colitis induced in a mouse model of azoxymethane (AOM)/dextran sulfate sodium (DSS), as demonstrated both by macroscopic and biochemical determinations. The oral administration of shikonin prevents weight loss and colorectum shortening. Histological analysis revealed a decrease both in the severity and extent of inflammation, together with an amelioration of the colonic architecture and the protection from the appearance of dysplasia. This was associated reduction in MPO activity together with the inhibition of COX-2 and iNOS expression. A possible mechanism of action which would be responsible for this protection is the inhibition of NF-κB activation, since we demonstrated the inhibition of the translocation of NF-κB-p65 subunit to the nucleus in the colon homogenate. As a positive control we examined the effect of oral administration of sulfasalazine (Ssz).