Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea.
The BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Mar;391(3):271-283. doi: 10.1007/s00210-017-1454-4. Epub 2017 Dec 20.
Flavone apigenin has an anti-inflammatory effect. We assessed whether apigenin may reduce the inflammatory mediator production, which is regulated by the Toll-like receptor-4-dependent activation of the Akt, mTOR, and NF-κB pathways, and activation of JNK and p38-MAPK in HEK001 keratinocytes and primary keratinocytes. Apigenin, the Akt inhibitor, Bay 11-7085, and N-acetylcysteine inhibited the lipopolysaccharide-stimulated production of cytokines IL-1β and IL-6 and chemokines CCL17 and CCL27; the expression of cyclooxygenase-2; the increase in the levels of Toll-like receptor-4, phosphorylated Akt, and mTOR; the activation of NF-κB; the activation of the JNK and p38-MAPK; and the production of reactive oxygen/nitrogen species in keratinocytes. Inhibitors of the c-JNK (SP600125) and p38-MAPK (SB203580) reduced lipopolysaccharide-induced production of inflammatory mediators and activation of the JNK and p38-MAPK in keratinocytes. These results show that apigenin may inhibit the lipopolysaccharide-caused inflammatory mediator production in keratinocytes by reducing the Toll-like receptor-4-dependent activation of Akt, mTOR, and NF-κB pathways, and activation of JNK and p38-MAPK. The suppressive effect of apigenin may be achieved by the inhibition of reactive oxygen/nitrogen species production. Additionally, apigenin appears to reduce the Akt, mTOR, and NF-κB pathway- and the JNK and p38-MAPK-mediated inflammatory skin diseases.
芹菜素具有抗炎作用。我们评估了芹菜素是否可能减少炎症介质的产生，炎症介质的产生受 Toll 样受体-4 依赖性激活的 Akt、mTOR 和 NF-κB 途径以及 JNK 和 p38-MAPK 的调节，以及在 HEK001 角质细胞和原代角质细胞中的激活。芹菜素、Akt 抑制剂 Bay 11-7085 和 N-乙酰半胱氨酸抑制了脂多糖刺激的细胞因子 IL-1β 和 IL-6 以及趋化因子 CCL17 和 CCL27 的产生；环氧合酶-2 的表达；Toll 样受体-4、磷酸化 Akt 和 mTOR 的水平增加；NF-κB 的激活；JNK 和 p38-MAPK 的激活；以及角质细胞中活性氧/氮物种的产生。JNK 的抑制剂（SP600125）和 p38-MAPK（SB203580）减少了脂多糖诱导的炎症介质产生和角质细胞中 JNK 和 p38-MAPK 的激活。这些结果表明，芹菜素可能通过减少 Akt、mTOR 和 NF-κB 途径以及 JNK 和 p38-MAPK 的激活，来抑制角质细胞中脂多糖引起的炎症介质产生。芹菜素的抑制作用可能是通过抑制活性氧/氮物种的产生来实现的。此外，芹菜素似乎可以减少 Akt、mTOR 和 NF-κB 途径以及 JNK 和 p38-MAPK 介导的炎症性皮肤疾病。
