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.

Abstract

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 (0.5-10 μg/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.

• Authors: 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
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 59 Pg. 55-66 (Sep 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23712098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Cyclopentanes
• NF-E2-Related Factor 2
• NF-kappa B
• NFE2L2 protein, human
• Reactive Oxygen Species
• lucidone
• HMOX1 protein, human
• Heme Oxygenase-1

Topics

• Anti-Inflammatory Agents, Non-Steroidal (isolation & purification, pharmacology)
• Antioxidants (isolation & purification, pharmacology)
• Cell Line
• Cell Nucleus (drug effects, metabolism)
• Cell Survival (drug effects)
• Cyclopentanes (isolation & purification, pharmacology)
• DNA Damage (drug effects)
• Ethnopharmacology
• Fruit (chemistry)
• Gene Silencing
• Heme Oxygenase-1 (chemistry, genetics, metabolism)
• Humans
• Keratinocytes (drug effects, immunology, metabolism)
• Lindera (chemistry)
• Lipid Peroxidation (drug effects)
• NF-E2-Related Factor 2 (agonists, antagonists & inhibitors, genetics, metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Protein Transport (drug effects)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Taiwan