title: Carnosic acid, a phenolic diterpene from rosemary, prevents UV-induced expression of matrix metalloproteinases in human skin fibroblasts and keratinocytes.
abstract: Exposure of the skin to ultraviolet (UV) irradiation induces photoageing through the up-regulation of matrix metalloproteinases (MMPs) and subsequent breakdown of extracellular matrices. Reactive oxygen species (ROS) and epidermal growth factor receptor (EGFR) activation play central roles in UV-induced MMP expression through initiating extracellular signal-regulated kinase (ERK)-mediated AP-1 signalling. We aimed to explore the effects of carnosic acid (CA), a phenolic diterpene from rosemary, on UV-induced MMP expression in human skin cells. Molecular mechanism underlying the effects of CA was also examined in the aspect of MMP expression, ERK/AP-1 pathway, ROS generation and EGFR activation. Human dermal fibroblast cell line (Hs68), primary normal human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (HEKs) were employed, and antiphotoageing effects of CA were assessed by Western blotting, quantitative real-time PCR and enzyme assays. CA significantly inhibited UVA- and UVB-induced expression of MMP-1, MMP-3 and MMP-9 in a concentration-dependent manner in Hs68 cells. UVB-induced ERK activation and the formation of transcription factor, AP-1, were significantly suppressed by CA. Among the upstream events of MMP expression, UVB-induced ROS generation was attenuated by CA, while EGFR activation was not affected. Confirming the antiphotoageing effects of CA through the suppression of UV-induced ROS generation, UVB-enhanced GADD45 expression, a marker for oxidative DNA damages was significantly reduced by CA. Inhibitory effects of CA on UVB-induced MMP expression could be also seen in HDFs and HEKs. Collectively, our study demonstrates that CA inhibits the UV-enhanced MMPs in human skin cells through the inhibition of ROS and the suppression of ERK/AP-1 activation.
authors.affiliation: Medical Beauty Research Institute, Amorepacific Corporation R&D Center, Yongin, Korea.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Park
authors.forename: Jiwon
authors.initials: J
authors.lastname: Han
authors.forename: Chang Seok
authors.initials: CS
authors.lastname: Lee
authors.forename: Baek Heung
authors.initials: BH
authors.lastname: Soo
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.forename: Hunjoo
authors.initials: H
authors.lastname: Ha
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D061251:Primary Cell Culture; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D027542:Rosmarinus / Q000737:chemistry*; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays; D000097642:GADD45 Proteins
chemical_list: D045784:Abietanes; D000975:Antioxidants; D018797:Cell Cycle Proteins; D004224:Diterpenes; D066246:ErbB Receptors; D020781:Matrix Metalloproteinase 1; D009687:Nuclear Proteins; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D017382:Reactive Oxygen Species; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C522360:MMP1 protein, human; C018381:salvin