composed mainly of neutrophils and macrophages, an effect that is accompanied by production of pro-inflammatory cytokines, like IL-1b, IL-6, TNF-a and IFN-c [4]. In addition, the recruitment of these cells from the vasculature to sites of inflammation is dependent on a multistep cascade of adhesive interactions, which are mediated by adhesion molecules and chemoattractants, such as, integrins/selectins and chemokines, respectively [5,6]. Over the past decade, a substantial amount of evidence has been generated to support a crucial role of leukocytes in the pathogenesis of colitis [7,8]. The process of leukocyte extravasa- tions is a critical step in the inflammatory response and is dependent on three different families {Barreiro, #603}. (1) Selectins belong to a family of three carbohydrate-recognizing molecules: E-selectin, which is mainly expressed on activated endothelium; P-selectin, which is expressed on platelets and the endothelium; and L-selectin, which is constitutively expressed on leukocytes [10]. Several studies using antibody blockade of selectins have demonstrated the relevant role of selectins in leukocyte rolling [11,12]. (2) Integrins comprise a family of 24 heterodimeric receptors, each of which is composed of an a- and a b-subunit. These molecules dynamically alter their adhesive properties through conformational changes (affinity) as well as through spatial redistribution on the cell surface and are fundamental molecules in cell migration [13,14]. Furthermore, integrins can recognize multiple ligands including proteins of the Euphol and Experimental Colitis extracellular matrix, cell surface glycoprotein as well as comple- ment factors and soluble components of the hemostatic and fibrinolytic cascade. (3) The major integrin ligands involved in leukocyte adhesion belong to the immunoglobulin superfamily [15] and include intercellular cell adhesion molecules (ICAM) 1–5, vascular cell adhesion molecule-1 (VCAM-1) and junctional adhesion molecules (JAMs), which are expressed on endothelial and other types of cells [16]. Thus, blocking adhesion molecules constitutes a potential and useful target for controlling leukocyte influx into the site of inflammation and consequently, leads to the development of new anti-inflammatory drugs. The tetracyclic triterpene euphol (Fig.1A) is the main constit- uent found in the sap of Euphorbia tirucalli, a plant belonging to the family Euphorbiaceae, and known in Brazilian traditional medicine as aveloz, a´rvore-do-la´pis, cega-olho or espinho-italiano. In the northeast region of Brazil, the latex of E. tirucalli is used as a folk therapy against syphilis, laxative agent, to control intestinal parasites, to treat asthma, cough, earache, rheumatism, cancer, chancre, epithelioma, sarcoma and skin tumors [17]. The bark/ latex of E. tirucalli presents pharmacological activities as mollus- cicide, antiherpetic and anti-mutagenic [17]. It also shows co- carcinogenic and anti-carcinogenic activities [18]. In addition, the sap of E. tirucalli showed relevant potential larvicide against Aedes aegypti and Culex quinquefasciatus, the most common dengue vector and lymphatic filariasis vector, respectively [19] and demonstrated Figure 1. Euphol ameliorates DSS-induced acute colitis. (A), Chemical structure of euphol. Mice received DSS for 5 days and drinking water for the next 2 days. Animals were orally treated by gavage with 3, 10, or 30 mg/kg of euphol twice a day from day 0 to day 7 (preventive treatment) or with 30 mg/kg from day 3 to day 7 (therapeutic treatment). Preventive or therapeutic oral treatment with euphol improved the disease activity index (DAI) score (B), reduced body weight loss (C) and colon macroscopic damage (D), and enhanced colon length (E) when compared with mice from the DSS group. Data are reported as means 6 S.E.M. of 8 to 10 mice per group and is representative of three independent experiments. #P,0.05 vs. control healthy group; *P,0.05 vs. DSS-treated group. doi:10.1371/journal.pone.0027122.g001 PLoS ONE | www.plosone.org 2 November 2011 | Volume 6 | Issue 11 | e27122