Amigó Maria, Payá Miguel, Braza-Boïls Aitana, De Rosa Salvatore, Terencio Maria Carmen
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain.
Life Sci. 2008 Jan 30;82(5-6):256-64. doi: 10.1016/j.lfs.2007.11.017. Epub 2007 Dec 5.
Avarol is a marine sesquiterpenoid hydroquinone with interesting pharmacological properties including anti-inflammatory and antipsoriatic effects. In the present study we evaluated the pharmacological effect of avarol on some inflammatory parameters related to the pathogenesis of psoriasis. Avarol inhibited tumor necrosis factor-alpha (TNF-alpha) generation in stimulated human monocytes (IC(50) 1 microM) and TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB)-DNA binding in keratinocytes. In the mouse air pouch model, administration of avarol produced a dose-dependent reduction of TNF-alpha generation (ED(50) 9.2 nmol/pouch) as well as of interleukin (IL)-1beta, prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) levels in pouch exudates. In the psoriasis-like model of 12-O-tetradecanoylphorbol-acetate-induced mouse epidermal hyperplasia, topical administration of avarol (0.6-1.2 micromol/site) reduced edema, myeloperoxidase activity, IL-1beta, IL-2 and eicosanoid levels in skin. Histopathological study confirmed the inhibition of epidermal hyperplasia as well as leukocyte infiltration. The reduction of cutaneous TNF-alpha by avarol was also detected by immunohistochemical analysis. Avarol was also capable of suppressing in vivo NF-kappaB nuclear translocation, determined in mouse skin. Our results suggested that antipsoriatic properties of avarol previously described could be mediated in part by the downregulation of several inflammatory biomarkers, such as TNF-alpha and NF-kappaB in psoriatic skin.
阿伐洛醇是一种具有有趣药理特性的海洋倍半萜对苯二酚，包括抗炎和抗银屑病作用。在本研究中，我们评估了阿伐洛醇对一些与银屑病发病机制相关的炎症参数的药理作用。阿伐洛醇抑制刺激的人单核细胞中肿瘤坏死因子-α（TNF-α）的产生（IC50为1 microM）以及TNF-α诱导的角质形成细胞中核因子-κB（NF-κB）-DNA结合的激活。在小鼠气囊模型中，给予阿伐洛醇可使气囊渗出物中TNF-α的产生呈剂量依赖性降低（ED50为9.2 nmol/气囊），同时也可降低白细胞介素（IL）-1β、前列腺素E2（PGE2）和白三烯B4（LTB4）的水平。在12-O-十四酰佛波醇-13-乙酸酯诱导的小鼠表皮增生的银屑病样模型中，局部给予阿伐洛醇（0.6-1.2 micromol/部位）可降低皮肤中的水肿、髓过氧化物酶活性、IL-1β、IL-2和类花生酸水平。组织病理学研究证实了表皮增生以及白细胞浸润受到抑制。通过免疫组织化学分析也检测到阿伐洛醇可降低皮肤中TNF-α的水平。阿伐洛醇还能够抑制在小鼠皮肤中测定的体内NF-κB核转位。我们的结果表明，先前描述的阿伐洛醇的抗银屑病特性可能部分是由银屑病皮肤中几种炎症生物标志物（如TNF-α和NF-κB）的下调介导的。
