Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Tokyo, Japan.
Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Tokyo, Japan.
Eur J Pharmacol. 2019 Feb 15;845:40-47. doi: 10.1016/j.ejphar.2018.12.036. Epub 2018 Dec 21.
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)-1β, 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.
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可供选择。根据一般指南，一线治疗方法包括局部类固醇；然而，这种治疗方法在应用部位有限制，以避免不良皮肤事件。因此，人们对开发新的治疗方法的需求增加。在日本，最近含有儿茶素的保健品的使用及其有益效果引起了关注。事实上，有几项研究已经研究了儿茶素的抗癌、抗肥胖、抗炎和抗氧化作用。在这项研究中，我们从天然（+）-儿茶素中合成了平面儿茶素（PC），并进一步对其进行了化学修饰，旨在阐明新型儿茶素衍生物的抗炎和抗氧化作用。甲氧基 PC（甲基 PC）和乙酰化 PC（乙酰 PC）被修饰以增加脂溶性。通过评估去除羟基自由基的能力，用电子自旋共振法研究了它们的抗氧化作用。在体外，抗氧化作用的顺序为 PC > （+）-儿茶素 > 乙酰 PC > 甲基 PC。此外，我们使用 1-氟-2,4-二硝基苯（DNFB）诱导的 BALB/c 小鼠过敏性接触性皮炎模型。我们的结果表明，儿茶素衍生物抑制了由 DNFB 诱导的耳部肿胀，其中乙酰 PC 的抑制作用大于 PC 和甲基 PC。此外，乙酰 PC 下调了耳组织中炎性细胞因子（包括肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-4）和髓过氧化物酶活性的 mRNA 水平。综上所述，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种有前途的新选择。
