The inflammatory bowel diseases (IBDs) are idiopathic chronic conditions caused by genetic and environmental factors that influence the immune response. Ulcerative colitis (UC) is among the most important IBD, primarily affecting the mucosa and submucosal layers of the colon, leading to clinically relevant recurrent episodes of bloody diarrhea, abdominal cramps, weight and appetite losses, anorexia and hyperthermia [1], [2], [3]. UC typically initiates in the rectal region and progresses to proximal colon, manifesting these clinically relevant symptoms. The traditional pharmacological treatment of UC (and other IBDs) involves the administration of 5-aminosalicylic acid (5-ASA), sulfasalazine, corticosteroids, antimicrobials, immunosuppressants and more recently, biological drugs such as anti-tumor necrosis factor (anti-TNF) agents, integrin receptor antagonists (IRAs) and interleukin (IL) inhibitors [4], [5].Nevertheless, the effectiveness of the treatment varies and is limited, resulting in remission rates around 50 %. Therefore, the search for novel treatment alternatives remains a theme of interest.

The role of histamine in the pathogenesis of UC has been demonstrated in several literature reports [6], [7], [8]. Increased levels of histamine are detected in the intestinal mucosa of IBD patients [9] and it is widely recognized as important pro-inflammatory factor in chronic inflammation. Therefore, by mitigating histamine's effects on intestinal tissue, it is possible to provide therapeutic benefits to patients suffering from IBDs.

Histamine effects are related to its action through four receptors, namely from H1 to H4 (H1R- H4R), which belong to G protein-coupled receptors family [10], [11]. The H1R, H2R and H4R (but not H3R) are expressed in the intestinal tissues and appear to be correlated with IBD pathophysiology. Experimental evidence shows that activation of H1R and H4R is involved in the development of UC, while the activation of H2R seems to promote protective effects. Although experimental data suggest that H1R antagonists or H2R agonists could provide therapeutic benefits in UC treatment, clinical evidence is not conclusive or significant. The role of histamine and its receptors on IBDs is discussed comprehensively by Neumann and Seifert [12], and more recently by Dvornikova et al. [13].

The H4R is known by its expression in inflammatory cells, and several studies have already shown its role on intestinal mucosa and participation in the development of IBDs [14], [15], [16], [17], particularly in mucosal damage and UC development [7]. In experimental models of UC, H4R blockade significantly reduced edema, myeloperoxidase levels and neutrophilic infiltrations in the intestinal tissue [18]. Treatment with H4R antagonists also reduced the levels of proinflammatory cytokines such as interleukins 5 and 6 (IL-5 e IL-6, respectively) on mesenteric lymphnodes and serum (IL-6), as well as reduced granulocyte infiltrations in the colon [19].

Recently, our group reported the anti-inflammatory effects of 1-[5-chloro-(2,3-dihydrobenzofuran-2-yl)methyl]-4-methylpiperazine (LINS01007), a H4R antagonist with submicromolar affinity (pKi 6.2) [20] with no important affinity at H1R or H2R (pKi < 5.0) [21].In murine asthma model, this compound has been shown to reduce eosinophilic infiltrations and cellularity in the bronchoalveolar lavage. Reduced expressions of cyclooxygenase 2 (COX-2), 5-lipoxygenase (5-LO), nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were also observed in the mice treated with LINS01007, as well as tissue thickness, mucus production and collagen deposition [22]. Although this compound has already shown interesting efficacy as anti-inflammatory agent, its efficacy against IBDs has not been assessed to date. Considering this, the effects of the treatment with LINS01007 on dextran sodium sulphate (DSS)-induced model of UC are reported in this work.