Biotin/sulfasalazine combination therapy alleviates acetic acid-induced ulcerative colitis in rats via modulation of S1PR1/NF-κB/IL-23/STAT3/COX-2 axis

Abstract

Abstract Ulcerative colitis (UC) is a chronic idiopathic mucosal inflammation of colon. The lack of effective remedies urges us to search for new remedies to effectively cure UC. The current study aims to explore the potential therapeutic effect of sulfasalazine (SLZ)/Biotin combination in ameliorating acetic acid (AA)-evoked UC in rats. SLZ (100 mg/kg), Biotin (6 mg/kg) and SLZ plus Biotin were administered orally for 8 days followed by injection of AA (2 mL, 3% v/v) intra-rectally to induce UC on the 8th day. SLZ/Biotin combination therapy attenuated AA-induced UC as proved by mitigation of pathological colonic abnormalities and decrease in disease activity index, colon mass index, colon weight/length ratio, LDH and CRP serum levels. This was associated with a considerable restoration of redox state in colon; MDA, NO and GSH contents. Furthermore, SLZ/Biotin combination therapy reduced colonic inflammation as confirmed by the remarkable decrement of S1P, S1PR1, IL-23, STAT3, and P-STAT3 colonic levels along with downregulation of colonic COX-2 and NF-κB protein expressions. Biotin as add-on therapy to SLZ markedly alleviates AA-induced UC via modulating S1P/S1PR1/NF-kB/ IL-23/STAT3 inflammatory signaling pathway with subsequent inhibition of COX-2.