title: 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.affiliation: Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: K J Senthil
authors.initials: KJ
authors.lastname: Kumar
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Tsai
authors.forename: Pin-Chun
authors.initials: PC
authors.lastname: Hung
authors.forename: Show-Huei
authors.initials: SH
authors.lastname: Chang
authors.forename: Heng-Wei
authors.initials: HW
authors.lastname: Lo
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Shen
authors.forename: Ssu-Ching
authors.initials: SC
authors.lastname: Chen
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Wang
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chou
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003517:Cyclopentanes / Q000302:isolation & purification / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D020834:Ethnopharmacology; D005638:Fruit / Q000737:chemistry; D020868:Gene Silencing; D051547:Heme Oxygenase-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D027443:Lindera / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013624:Taiwan
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003517:Cyclopentanes; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C529637:lucidone; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Anti-inflammation; Antioxidant; Lindera erythrocarpa; Lucidone; Nrf2