Lucidone protects human skin keratinocytes against free radical-induced oxidative damage and inflammation through the up-regulation of HO-1/Nrf2 antioxidant genes and down-regulation of NF-¦ÊB signaling pathway

详细信息    查看全文

• 作者：K.J. Senthil Kumar ; Hsin-Ling Yang ; Yu-Cheng Tsai ; Pin-Chun Hung ; Show-Huei Chang ; Heng-Wei Lo ; Pei-Chun Shen ; Ssu-Ching Chen ; Hui-Min Wang ; Sheng-Yang Wang ; Chih-Wei Chou ; You-Cheng Hseu
• 关键词：Lindera erythrocarpa ; Lucidone ; Antioxidant ; Anti-inflammation ; Nrf2
• 刊名：Food and Chemical Toxicology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：59
• 期：Complete
• 页码：55-66
• 全文大小：2202 K

文摘

We investigated the protective effects of lucidone, a naturally occurring cyclopentenedione isolated from the fruits of Lindera erythrocarpa Makino, against free-radical and inflammation stimulator 2,2¡ä-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress in human keratinocyte (HaCaT) cells, with the aim of revealing the possible mechanisms underlying the protective efficacy. Lucidone pretreatment (0.5-10 ¦Ìg/mL) markedly increased HaCaT cell viability and suppressed AAPH-induced reactive oxygen species (ROS) generation, lipid peroxidation, and DNA damage. Notably, the antioxidant potential of lucidone was directly correlated with the increased expression of an antioxidant gene, heme oxygenase 1 (HO-1), which was followed by the augmentation of the nuclear translocation and transcriptional activation of NF-E2-related factor-2 (Nrf2), with or without AAPH. Nrf2 knockdown diminished the protective effects of lucidone. We also observed that lucidone pretreatment inhibited AAPH-induced inflammatory chemokine prostaglandin E₂ (PGE₂) production and the expression of cyclooxygenase-2 (COX-2) in HaCaT cells. Lucidone treatment also significantly inhibited AAPH-induced nuclear factor-¦ÊB (NF-¦ÊB) activation and suppressing the degradation of inhibitor-¦ÊB (I-¦ÊB). Furthermore, lucidone significantly diminished AAPH-induced COX-2 expression through the down-regulation of the extracellular signal-regulated kinase (ERK) and p38 MAPK signaling pathways. Therefore, lucidone may possess antioxidant and anti-inflammatory properties and may be useful for the prevention of free radical-induced skin damage.