Inhibition of UVA irradiation-modulated signaling pathways by rutaecarpine, a quinazolinocarboline alkaloid, in human keratinocytes

Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by ultraviolet A irradiation-associated generation of reactive oxygen species. In this study, we investigated the effects of synthetic rutaecarpine, which is also found in Evodia rutaecarpa, on the ultraviolet A-induced changes in the expression of gelatinases: matrix metalloproteinase (MMP)-2 and MMP-9 using HaCaT human keratinocytes as a model cellular system. Ultraviolet A irradiation of HaCaT cells increased the gelatinolytic activities of MMP-2 and MMP-9, which was significantly suppressed by the pretreatment with rutaecarpine. In addition, rutaecarpine significantly suppressed the ultraviolet A-induced enhanced expression of MMP-2 and MMP-9 proteins and mRNAs. Rutaecarpine also inhibited the H2O2-induced increase in the expression of MMP-2 and MMP-9. Furthermore, rutaecarpine decreased the ultraviolet A-induced increased generation of reactive oxygen species. Taken together, these results suggest that rutaecarpine inhibited ultraviolet A-induced reactive oxygen species generation, resulting in the enhanced expression of MMP-2 and MMP-9 in human skin cells. These results further suggest that ruetaecarpine may be useful in the prevention of ultraviolet A-induced photoaging. (C) 2004 Elsevier B.V. All rights reserved.