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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.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Park M,Han J,Lee CS,Soo BH,Lim KM,Ha H

doi

10.1111/exd.12138

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

336-41

issue

eissn

0906-6705

issn

1600-0625

journal_volume

pub_type

杂志文章

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Carnosic acid, a phenolic diterpene from rosemary, prevents UV-induced expression of matrix metalloproteinases in human skin fibroblasts and keratinocytes.