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 ( MMP s) 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 ( HDF s) and normal human epidermal keratinocytes ( HEK s) 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 H s68 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 GADD 45 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 HDF s and HEK s. Collectively, our study demonstrates that CA inhibits the UV ‐enhanced MMP s in human skin cells through the inhibition of ROS and the suppression of ERK / AP ‐1 activation.