title: Inhibition of matrix metalloproteinase-1 induced by oxidative stress in human keratinocytes by mangiferin isolated from Anemarrhena asphodeloides.
abstract: Oxidative stress is related to the synthesis of matrix metalloproteinases (MMPs), which cause skin aging. The protective effects of mangiferin derived from Anemarrhena asphodeloides were investigated against hydrogen peroxide (H(2)O(2))-induced damage using human skin keratinocyte (HaCaT) cells. Mangiferin was found to scavenge intracellular reactive oxygen species (ROS), superoxide radicals, and hydroxyl radicals. ROS regulate MMPs gene expression and activation of proenzymes. Mangiferin inhibited H(2)O(2)-induced MMP-1 gene expression and protein levels as well as its activity. Moreover, it abrogated mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway and stress-activated protein kinase/extracellular signal-regulated kinase (SEK)-c-JUN N-terminal kinase (JNK) pathway, which are induced by H(2)O(2) treatment. And, it inhibited DNA binding activity of activator protein-1 (AP-1), a transcription factor of MMP-1 and downstream of ERK and JNK. Finally, it protected the human skin keratinocytes from H(2)O(2)-induced cell death. Taken together, these results indicate that mangiferin attenuated H(2)O(2)-induced MMP-1 activation via inhibition of ERK and JNK pathway and AP-1.
authors.affiliation: Aging Research Center, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: Sungwook
authors.initials: S
authors.lastname: Chae
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: Ui Joung
authors.initials: UJ
authors.lastname: Youn
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.forename: Jun Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D031403:Anemarrhena / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D044004:Xanthones / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D018808:Transcription Factor AP-1; D044004:Xanthones; C013592:mangiferin; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1