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-κB signaling pathway

• Published in: Food and chemical toxicology 2013-09, Vol.59, p.55-66
• Main Authors: Senthil Kumar, K.J., Yang, Hsin-Ling, Tsai, Yu-Cheng, Hung, Pin-Chun, Chang, Show-Huei, Lo, Heng-Wei, Shen, Pei-Chun, Chen, Ssu-Ching, Wang, Hui-Min, Wang, Sheng-Yang, Chou, Chih-Wei, Hseu, You-Cheng
• Format: Article
• Language: English
• Subjects: Anti-inflammation; anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antioxidant; antioxidant activity; antioxidants; Antioxidants - isolation & purification; Antioxidants - pharmacology; Biological and medical sciences; Cell Line; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Survival - drug effects; cell viability; chemokines; Cyclopentanes - isolation & purification; Cyclopentanes - pharmacology; DNA damage; DNA Damage - drug effects; Ethnopharmacology; Food toxicology; Fruit - chemistry; fruits; Gene Silencing; genes; heme oxygenase (biliverdin-producing); Heme Oxygenase-1 - chemistry; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; inflammation; keratinocytes; Keratinocytes - drug effects; Keratinocytes - immunology; Keratinocytes - metabolism; Lindera - chemistry; Lindera erythrocarpa; lipid peroxidation; Lipid Peroxidation - drug effects; Lucidone; Medical sciences; mitogen-activated protein kinase; NF-E2-Related Factor 2 - agonists; NF-E2-Related Factor 2 - antagonists & inhibitors; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Nrf2; oxidative stress; Oxidative Stress - drug effects; prostaglandin synthase; prostaglandins; protective effect; Protein Transport - drug effects; reactive oxygen species; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; signal transduction; Signal Transduction - drug effects; Taiwan; Toxicology; transcription factor NF-kappa B; transcriptional activation
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.04.055

•Lucidone protected human skin keratinocytes (HaCaT) from AAPH-induced cell death.•Lucidone inhibited AAPH-induced ROS generation, lipid peroxidation, and DNA damage.•The antioxidant potential of lucidone was directly correlated with Nrf2 activity.•Lucidone inhibited AAPH-induced inflammatory PGE2 production and COX-2 expression.•Lucidone suppressed AAPH-induced NF-κB and MAPKs signaling pathways. 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′-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 (0.5–10μg/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-κB (NF-κB) activation and suppressing the degradation of inhibitor-κB (I-κB). 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.