Ertugliflozin ameliorates experimentally-induced colitis in rats by regulating the interplay between M1/M2 macrophage polarization, tight junction proteins, and MicroRNA 155 expression.

Ulcerative colitis (UC) is a persistent inflammatory condition marked by the destruction of the intestinal mucosal barrier, infiltration of inflammatory cells, and ulceration. M1/M2 macrophage polarization plays an imperative function in the regulation of inflammation through the nuclear factor-kappa B (NFκB) signaling pathway and modulating microRNA-155 (miR-155). Recent studies have highlighted the anti-ulcerogenic and colo-protective properties of sodium-glucose co-transporter-2 (SGLT2) inhibitors. However, the potential protective and therapeutic effects of ertugliflozin (Ertu), an SGLT2 inhibitor, in UC have not yet been clarified. Therefore, the present research sought to investigate the potential role of Ertu in mitigating acetic acid (AA)-induced UC in rats. Forty-two adult Wistar rats were allocated into seven groups: control, Ertu (10 mg/kg), AA, AA+ Ertu (1, 5, and 10 mg/kg), and AA+ sulfasalazine (Sulfa) (100 mg/kg); all received oral treatments daily for 7 days. Pre-treatment with Ertu mitigated histopathological alterations and enhanced macroscopic assessments. Ertu suppressed the expression of NF-κB p65 and miRNA-155, promoting macrophage polarization towards M2 phenotype, as witnessed by increased expression of CD206, Fizz-1, Ym-1, and Arg-1, along with elevated IL-10 protein content. It reduced the expression of CD86 and MCP-1, besides the levels of TNF-α, IL-1β and iNOS. Moreover, Ertu improved intestinal epithelial integrity by upregulating tight junction proteins, comprising claudin-1, occludin and ZO-1. Ertu also demonstrated anti-apoptotic effects by reducing BAX meanwhile increasing BCL2. Notably, Ertu (10 mg/kg) exhibited therapeutic effects comparable to the standard treatment, Sulfa, underscoring its potential as a distinctive and valuable option for UC management.