The 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 FINDINGS:
Colitis 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/SIGNIFICANCE: