Ulcerative colitis is a chronic disease and characterized by relapsing and remitting mucosal inflammation [1]. The specific mechanism of ulcerative colitis is still unclear, but the damages of intestinal epithelial cells, mucus barrier and epithelial barrier are closely related to the occurrence of colitis. Presently, the clinical drugs for ulcerative colitis treatment include anti-inflammatory medications, immune system suppressors, and biologics etc. Among them, mesalazine is first-line drug for the treatment of mild to moderate colitis, and the maintenance therapy for moderate to severe disease relies on immunosuppressants, biologics etc [2].

AMP activated protein kinase (AMPK) activity is associated with intestinal barrier function. It has been reported that AMPK activation promotes the tight junction assembly by direct phosphorylation of proteins composing apical junctions, junctional anchors, and cytoskeletons [3]. Furthermore, AMPK activation promotes intestinal epithelial differentiation and facilitates cell polarity establishment through promoting the expression of caudal type homeobox 2 (CDX2) which is a key transcription factor governing differentiation of intestinal epithelial cells [4]. JAK/STAT3 signaling is another important pathway involved in the pathogenesis of ulcerative colitis, and inhibition of JAK/STAT3 alleviates intestinal inflammation [5]. Tofacitinib as an oral JAK inhibitor has been used for moderate to severe colitis treatment. Metformin has been reported to improve colitis through inhibiting STAT3 signaling pathway [6], in addition to AMPK activation [7].

Nitazoxanide is an FDA-approved oral antiprotozoal drug [8], and also used to treat patients with metronidazole resistant Clostridium difficile colitis [9]. Nitazoxanide inhibits the abnormally elevated level of IL-6 in in vivo and in vitro inflammation models [10]. Our previous studies found that both nitazoxanide and its metabolite tizoxanide activated AMPK, inhibited NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and inhibited STAT3 [[11], [12], [13]], indicating nitazoxanide would be therapeutic for ulcerative colitis. In the present study, we investigated the effect of nitazoxanide on DSS-induced colitis in mice and the underlying mechanism.