摘要/Abstract

奥沙普秦是临床常用抗炎药物, 口服易造成胃肠穿孔, 与其分子结构中羧酸基团引起的局部刺激密切相关. 丹皮酚是牡丹的有效成分, 有抗炎、抗氧化的功效. 合成了奥沙普秦丹皮酚酯(OPE), 试图在避免胃肠道并发症的同时, 提高其抗炎效果. 通过12-O-十四烷基佛波醇-13-乙酸酯(TPA)诱导的小鼠耳水肿模型评价了OPE的局部抗炎作用. 结果显示局部应用OPE可有效改善TPA诱导的耳廓肿胀, 抗炎效果是奥沙普秦的2倍, 是丹皮酚的4倍. 而且OPE可有效改善耳片组织IL-1β, IL-6和TNF-α的表达, 效果优于奥沙普秦和丹皮酚. 进一步研究显示OPE可通过阻断IκB激酶(IKK)活性来下调kappa-κB (NF-κB)的活性.
关键词: 奥沙普秦, 丹皮酚, 炎症, 耳廓肿胀模型
Oxaprozin is a common anti-inflammatory drug in the clinic. Oral medication of oxaprozin potentially induces the GI perforation, which is caused by the local irritation of its carboxylic acid group. Paeonol is an active ingredient of peony, and has anti-inflammatory and anti-oxidant effects. So oxaprozin-paeonol ester (OPE) was designed to avoid the GI complications and enhence corresponding anti-inflammatory. The topical anti-inflammatory effects of OPE was evaluated in a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results showed that topical treatment of OPE could effectively improve the TPA-induced ear edema and its anti-inflammatory effect is 2 times higher than that of oxaprozin and 4 times than that of paeonol. Moreover, OPE treatment could effectively mitigate the expression of IL-1β, IL-6, and TNF-α, and its effect is better than that of oxaprozin or paeonol. Furthor study demonstrated that topical treatment of OPE could obviously down-regulate the activation of factor kappa-κB (NF-κB) by blocking IκB kinase (IKK) activities. Accordingly, OPE might be used as a promising anti-inflammatory agent for inflammation-associated skin diseases.
Key words: Oxaprozin, Paeonol, Inflammatory, Ear edema mode


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