College of Pharmacy, Keimyung University, Daegu 704-701, South Korea.
Biochem Biophys Res Commun. 2013 Sep 6;438(4):721-7. doi: 10.1016/j.bbrc.2013.07.110. Epub 2013 Aug 1.
Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.
姜黄色素（TQ）是黑种草中的一种活性成分，据报道具有抗炎和化学预防特性。本研究旨在阐明姜黄色素在小鼠皮肤中抗炎和抗氧化活性的分子机制。用 TQ 预处理雌性 HR-1 无毛小鼠皮肤可减弱 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的环氧化酶-2（COX-2）表达。TQ 通过阻断 TPA 处理的小鼠皮肤中 IκBα 的磷酸化和随后的降解来减少核易位和核因子-κB（NF-κB）的 DNA 结合。TQ 预处理可减弱 Akt、c-Jun-N-末端激酶和 p38 丝裂原活化蛋白激酶的磷酸化，但不减弱细胞外信号调节激酶-1/2 的磷酸化。此外，TQ 的局部应用可诱导小鼠皮肤中血红素加氧酶-1、NAD（P）H-醌氧化还原酶-1、谷胱甘肽-S-转移酶和谷氨酸半胱氨酸连接酶的表达。综上所述，TQ 对 TPA 诱导的 COX-2 表达和 NF-κB 激活的抑制作用及其诱导细胞保护蛋白表达的能力为 TQ 在无毛小鼠皮肤中的抗炎和抗氧化作用提供了机制基础。
