Preventive and Therapeutic Euphol Treatment Attenuates Experimental Colitis in Mice

Abstract

BackgroundThe tetracyclic triterpene euphol is the main constituent found in the sap of Euphorbia tirucalli. This plant is widely known in Brazilian traditional medicine for its use in the treatment of several kinds of cancer, including leukaemia, prostate and breast cancers. Here, we investigated the effect of euphol on experimental models of colitis and the underlying mechanisms involved in its action.Methodology/Principal FindingsColitis was induced in mice either with dextran sulfate sodium (DSS) or with 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the effect of euphol (3, 10 and 30 mg/kg) on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, enzyme-Linked immunoabsorbent assay (ELISA), real time-polymerase chain reaction (RT-PCR) and flow cytometry. Preventive and therapeutic oral administration of euphol attenuated both DSS- and TNBS-induced acute colitis as observed by a significant reduction of the disease activity index (DAI), histological/microscopic damage score and myeloperoxidase (MPO) activity in colonic tissue. Likewise, euphol treatment also inhibited colon tissue levels and expression of IL-1β, CXCL1/KC, MCP-1, MIP-2, TNF-α and IL-6, while reducing NOS2, VEGF and Ki67 expression in colonic tissue. This action seems to be likely associated with inhibition of activation of nuclear factor-κB (NF-κB). In addition, euphol decreased LPS-induced MCP-1, TNF-α, IL-6 and IFN-γ, but increased IL-10 secretion from bone marrow-derived macrophages in vitro. Of note, euphol, at the same schedule of treatment, markedly inhibited both selectin (P- and E-selectin) and integrin (ICAM-1, VCAM-1 and LFA-1) expression in colonic tissue.Conclusions/SignificanceTogether, these results clearly demonstrated that orally-administered euphol, both preventive or therapeutic treatment were effective in reducing the severity of colitis in two models of chemically-induced mouse colitis and suggest this plant-derived compound might be a potential molecule in the management of inflammatory bowel diseases.

Maresin 1, a Proresolving Lipid Mediator Derived from Omega-3 Polyunsaturated Fatty Acids, Exerts Protective Actions in Murine Models of Colitis

“…All animals were examined once a day for body weight loss. At the end of the 72 h, the mice were euthanized and colons were removed and examined using the criteria previously established for TNBS-induced colitis (25,26). The animals were treated e.v.…”

Fatty Acid Synthase Inhibitor C75 Ameliorates Experimental Colitis

“…Chemokines, such as macrophage inflammatory protein (MIP)-2 and keratinocyte-derived chemokine (KC), attracting neutrophil transmigration across mucosal epithelia is a hallmark of several inflammatory diseases, including IBD (23,24). The mRNA levels of MIP-2 and KC in colons dramatically increased to 326-and 28-fold, respectively, after DSS exposure, whereas their levels were significantly inhibited by 78.2% and 68.0%, respectively, with C75 treatment ( Figures 4A, B).…”

Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression

“…The anti-inflammatory effects of euphol have been demonstrated to be associated with the inhibition of the activation of nuclear factor-κB (14), downregulation of tumor necrosis factor-α and cyclooxygenase-2 (15), inhibition of the T cell-mediated immune response (15), and the reduction of protein kinase C/extracellular signal-regulated protein kinase signaling activation (16). In addition to the antiviral and anti-inflammatory effects, the antitumor effects of euphol have also been observed.…”