Anti-inflammatory effects of new catechin derivatives in a hapten-induced mouse contact dermatitis model
Anti-inflammatory effects of new catechin derivatives in a hapten-induced mouse contact dermatitis model
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DOI：
10.1016/j.ejphar.2018.12.036
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发表时间：
2019-02-15
影响因子：
5
通讯作者：
Iwai, Shinichi
中科院分区：
文献类型：
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作者：
Nakano, Eriko;Kamei, Daisuke;Iwai, Shinichi
接触性皮炎是一种常见的皮肤病，皮肤科医生有多种治疗方法。根据一般指南，一线治疗涉及局部类固醇；然而，这种治疗有应用部位的限制，以避免不良皮肤事件。因此，对新疗法的开发存在更大的需求。在日本，最近含儿茶素的健康食品的使用及其有益效果引起了人们的注意。事实上，一些研究已经检测了儿茶素的抗癌、抗肥胖、抗炎和抗氧化作用。在本研究中，我们以天然的(+)-儿茶素为原料合成了平面儿茶素(PC)，并对其进行了进一步的化学修饰，以期阐明新型儿茶素衍生物的抗炎和抗氧化作用。对甲基化PC(甲基PC)和乙酰化PC(乙酰PC)进行了修饰，以增加脂类的溶解度。用电子自旋共振检测了它们的抗氧化作用，评价了它们清除羟基自由基的能力。体外抗氧化作用大小顺序为：PC>；(+)-儿茶素>；乙酰基PC>；甲基PC。此外，我们使用了1-氟-2，4-二硝基苯(DNFB)诱导的BALB/c小鼠变态反应性接触性皮炎模型。结果表明，儿茶素衍生物对DNFB所致小鼠耳肿胀有明显的抑制作用，其中乙酰PC的抑制作用强于PC和甲基PC。此外，乙酰PC还下调了DNFB处理的小鼠耳组织中炎性细胞因子，包括肿瘤坏死因子-α、白介素1-β和白介素4的mRNA水平，以及髓过氧化物酶的活性。总而言之，我们的新发现表明儿茶素衍生物可能是治疗接触性皮炎的一个有前途的新选择。
Contact dermatitis is a common skin disease, with various treatments available to dermatologists. According to general guidelines, the first line of treatment involves topical steroids; however, this treatment has application-site restrictions in order to avoid adverse cutaneous events. Accordingly, increased demand exists for the development of new treatments. In Japan, the recent use of catechin-containing health foods and their beneficial effects has attracted attention. Indeed, several studies have examined the anticancer, anti-obesity, anti-inflammatory, and antioxidant effects of catechins. In this study, we synthesized planar catechin (PC) from natural ( + )-catechin, and further chemically modified it with the intent to clarify the anti-inflammatory and antioxidant effects of new catechin derivatives. Methylate-PC (methyl PC) and acetylate-PC (acetyl PC) were modified to increase lipid solubility. Their antioxidant effects were examined with electron spin resonance by evaluating the ability to remove hydroxyl radicals. In vitro, the antioxidant effects were in the order of PC > ( + )-catechin > acetyl PC > methyl PC. In addition, we used a 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis model in BALB/c mice. Our results demonstrated that catechin derivatives inhibited ear swelling induced by DNFB, with acetyl PC demonstrating a greater inhibitory effect than PC and methyl PC. Moreover, acetyl PC downregulated the mRNA levels of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-4, as well as myeloperoxidase activity, in the ear tissue of DNFB-treated mice. Collectively, our novel findings suggest that catechin derivatives may be a promising new choice for the treatment of contact dermatitis.