title: Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress.
abstract: Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora, has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation.
authors: Graduate Institute of BioMedical Sciences, Chang Gung University.
authors: Zih-Chan
authors: ZC
authors: Lin
authors: Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan; Division of Basic Medical Sciences, Department of Nursing, Chang Gung Institute of Technology and Chronic Diseases and Health Promotion Research Center, Chiayi.
authors: Chiang-Wen
authors: CW
authors: Lee
authors: Division of Neonatology and Pediatric Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Yunlin.
authors: Ming-Horng
authors: MH
authors: Tsai
authors: Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung.
authors: Horng-Huey
authors: HH
authors: Ko
authors: Graduate Institute of BioMedical Sciences, Chang Gung University; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan.
authors: Jia-You
authors: JY
authors: Fang
authors: Center for Drug Abuse and Addiction, China Medical University Hospital; Center for Drug Abuse and Addiction, China Medical University, Taichung.
authors: Yao-Chang
authors: YC
authors: Chiang
authors: Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung; Center for Lipid Biosciences, Kaohsiung Medical University Hospital.
authors: Chan-Jung
authors: CJ
authors: Liang
authors: Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi.
authors: Lee-Fen
authors: LF
authors: Hsu
authors: Department of Dermatology, College of Medicine, Kaohsiung Medical University; Department of Dermatology, Kaohsiung Medical University Hospital.
authors: Stephen Chu-Sung
authors: SC
authors: Hu
authors: Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung; Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, Republic of China.
authors: Feng-Lin
authors: FL
authors: Yen
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003460:Crystallization; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D005079:Excipients; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility; D034421:Sus scrofa
chemical_list: D005079:Excipients; D047309:Flavones; D016328:NF-kappa B; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; C503624:eupafolin; D015232:Dinoprostone
keywords: cyclooxygenase-2; eupafolin; keratinocytes; nanoparticles; oxidative stress; particulate matter