Department of Pharmacology, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, Santa Catarina, Brazil.
Eur J Pharmacol. 2013 Jan 5;698(1-3):413-20. doi: 10.1016/j.ejphar.2012.10.019. Epub 2012 Oct 23.
Inflammation underlies the development and progression of a number of skin disorders including psoriasis, atopic dermatitis and cancer. Therefore, novel antiinflammatory agents are of great clinical interest for prevention and treatment of these conditions. Herein, we demonstrated the underlying molecular mechanisms of the antiinflammatory activity of euphol, a tetracyclic triterpene isolated from the sap of Euphorbia tirucalli, in skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice. Topical application of euphol (100 μg/ear) significantly inhibited TPA-induced ear edema and leukocyte influx through the reduction of keratinocyte-derived chemokine (CXCL1/KC) and macrophage inflammatory protein (MIP)-2 levels. At the intracellular level, euphol reduced TPA-induced extracellular signal-regulated protein kinase (ERK) activation and cyclooxygenase-2 (COX-2) upregulation. These effects were associated with euphol's ability to prevent TPA-induced protein kinase C (PKC) activation, namely PKCα and PKCδ isozymes. Our data indicate that topical application of euphol markedly inhibits the inflammatory response induced by TPA. Thus, euphol represents a promising agent for the management of skin diseases with an inflammatory component.
炎症是许多皮肤疾病（包括银屑病、特应性皮炎和癌症）发展和进展的基础。因此，新型抗炎药物对于这些疾病的预防和治疗具有重要的临床意义。在此，我们展示了从Euphorbia tirucalli 的树液中分离出的四环三萜 euphol 抑制由 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的皮肤炎症的抗炎活性的潜在分子机制。在小鼠中，euphol（100 μg/耳）的局部应用通过降低角质形成细胞衍生趋化因子（CXCL1/KC）和巨噬细胞炎症蛋白（MIP）-2 水平，显著抑制 TPA 诱导的耳肿胀和白细胞浸润。在细胞内水平，euphol 降低了 TPA 诱导的细胞外信号调节激酶（ERK）激活和环氧化酶-2（COX-2）上调。这些作用与 euphol 防止 TPA 诱导的蛋白激酶 C（PKC）激活有关，即 PKCα 和 PKCδ 同工型。我们的数据表明，局部应用 euphol 可显著抑制 TPA 诱导的炎症反应。因此，euphol 代表了一种有前途的治疗具有炎症成分的皮肤疾病的药物。
