Protective effect of (E)-(2,4-dihydroxy)-α-aminocinnamic acid, a hydroxy cinnamic acid derivative, in an ulcerative colitis model induced by TNBS.

Abstract

Ulcerative colitis (UC) is a multifactorial disease that causes long-lasting inflammation and ulcers in the digestive tract. UC is the most common form of inflammatory bowel disease (IBD). The current treatment for mild-to-moderate UC involves the use of 5-aminosalicylates (5-ASA), but much of this compound is unabsorbed and metabolized by N-acetylation. Several efforts have since been made to evaluate new molecules from synthetic or natural sources. Recently, it was reported that (E)-(5-chloro-2-hydroxy)-α-aminocinnamic acid (2c) and (E)-(2,4-dihydroxy)-α-aminocinnamic acid (2f) are as good or better myeloperoxidase (MPO) inhibitors and antioxidants than 5-ASA. Then, the present study aimed to evaluate the protective effects of 2c and 2f on a rat model of UC induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The results showed that TNBS caused the induction of colonic ulcers, as well as a significant increase in MPO activity and malondialdehyde (MDA) and a decrease in glutathione (GSH) content. The administration of 2f, 2c and 5-ASA, decreased the ulcers presence, inhibited MPO peroxidation activity and MPO presence (as determined by immunofluorescence), and increased GSH and reduced MDA content. However, 2f was better than 2c and 5-ASA, then, the principal mechanism by which 2f presented a protective effect in a UC model induced by TNBS in rats is by inhibiting MPO activity and due to its antioxidant activity.