A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon

Abstract

In previous reports, a novel colon-specific prodrug, 5-aminosalicyltaurine (5-ASA-Tau) administered orally, is successfully delivered to and liberates 5-aminosalicylic acid (5-ASA) and taurine in the inflamed large intestine of rats. Furthermore, the prodrug ameliorates the 2,4,6-trinitrobenzene-sulfonic acid-induced colitis, and taurine acts not only as a carrier but also as an active therapeutic agent. In this study, we investigated the anti-inflammatory properties of the prodrug at a molecular level. After rectal administration of taurine, formation of taurine chloramine (TauCl) in the inflamed colonic tissue was examined using high-performance liquid chromatography. In human colon epithelial cell lines, nuclear factor-B (NF-B) activity was accessed using an NF-B-dependent luciferase reporter gene. Protein levels were monitored by Western blotting. DNA binding activity of the NF-B subunit p65 was determined using a DNA binding assay kit. A millimolar level of TauCl was formed in the inflamed tissue. TauCl inhibited tumor necrosis factor (TNF)-dependent NF-B activation by modifying thiol(s) on p65 and blocking DNA binding. In addition, 5-ASA inhibited phosphorylation of p65 at serine 536, which is critical for transcriptional activity of NF-B. Furthermore, combined TauCl/5-ASA treatment additively inhibited TNF-dependent NF-B activation. Together, our data suggest that the colon-specific carrier taurine contributes to the clinical effect of the prodrug by potentiating the inhibitory effect of the active ingredient 5-ASA on a major proinflammatory signal, TNF-dependent NF-B activation in the inflamed large intestine.

Novel protective role of curcumin and taurine combination against experimental hepatocarcinogenesis

“…Furthermore, another study using a taurine derivative (taurine chloramines) demonstrated that taurine was able to regulate the synthesis of proinflammatory cytokines, thus suggesting that taurine may have a role in the initiation and propagation of the immune response (63). In addition, a previous study reported that the levels of IL-2 and IFN-γ were markedly elevated following treatment with curcumin and taurine, and were approximately equal to the control untreated levels (64).…”

Potential for amino acids supplementation during inflammatory bowel diseases

“…79 In addition, in vivo and in vitro studies evaluated the effects of a prodrug 5-aminosalicyltaurine which had a protective role in TNBS-induced colitis 80 and limited inflammatory response in cultured cells. 81 This prodrug appears to be more effective than the reference drug 5-ASA. 80 …”

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

“…These results are similar to the results described by Fiorucci et al [38] . Furthermore, Kim et al showed that 5-ASA attenuated TNF-dependent NF-kB activation, which may be critical during intestinal inflammation [39] . Considering these results, and the strong correlation between the intestinal levels of IFN-γ and TNF-α and the amount of EB, we hypothesize that balsalazine protects the intestinal mucosal barrier partly by inhibiting the proinflammatory cytokines.…”