title: Caffeic acid and ferulic acid inhibit UVA-induced matrix metalloproteinase-1 through regulation of antioxidant defense system in keratinocyte HaCaT cells.
abstract: Ultraviolet A (UVA) plays a vital role in the pathogenesis of premature skin aging through keratinocyte cytotoxicity and degradation of collagen, a main component of the extracellular matrix providing structural support. Oxidative stress caused by UVA irradiation can mediate induction of matrix metalloprotease-1 (MMP-1), a major enzyme responsible for collagen damage. Protection against UV-mediated disturbance of antioxidant defense system has been proposed as a possible mechanism by which botanical compounds slow down skin aging process. This study therefore aimed to assess inhibitory effects of caffeic acid (CA) and ferulic acid (FA), powerful plant-based phenolic antioxidants, on UVA-induced cytotoxicity and MMP-1 activity and mRNA level through modulation of antioxidant defense mechanism in immortalized human keratinocyte (HaCaT) cells. Pretreatment of the cells with CA or FA prior to UVA irradiation inhibited cytotoxicity, induction of MMP-1 activity and mRNA and oxidant formation. Moreover, CA and FA were able to up-regulate glutathione (GSH) content, γ-glutamate cysteine ligase (γ-GCL) mRNA as well as activities and mRNA expression of catalase and glutathione peroxidase (GPx) in irradiated cells. In conclusion, CA and FA provided protective effects on UVA-mediated MMP-1 induction in HaCaT cells possibly through restoration of antioxidant defense system at the cellular and molecular level.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Thanyawan
authors.initials: T
authors.lastname: Pluemsamran
authors.forename: Tasanee
authors.initials: T
authors.lastname: Onkoksoong
authors.forename: Uraiwan
authors.initials: U
authors.lastname: Panich
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D003373:Coumaric Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000096:biosynthesis; D015595:Skin Aging / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D003373:Coumaric Acids; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; C004999:ferulic acid; D002374:Catalase; D005979:Glutathione Peroxidase; D020781:Matrix Metalloproteinase 1; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; C040048:caffeic acid