Inhibition of ultraviolet-A-modulated signaling pathways by asiatic acid and ursolic acid in HaCaT human keratinocytes

Premature aging of the skin (photoaging) is a well-documented consequence of exposure to ultraviolet-A (UVA). Enhanced generation of reactive oxygen species and induction of matrix metalloproteinases (MMPs) appear to be the most important components of UVA-modulated signal transduction pathways, ultimately leading to photoaging. In this study, we investigated the effects of asiatic acid and ursolic acid, triterpene compounds, on the UVA-modulated signaling pathways using HaCaT human keratinocytes as a model cellular system. In the cells, we confirmed that UVA irradiation induced oxidative stress and increased the expression of MMP-2. Asiatic acid and ursolic acid significantly suppressed the UVA-induced reactive oxygen species production and lipid peroxidation. Pretreatment with asiatic acid or ursolic acid significantly reduced the UVA-induced activation and expression of MMP-2. In addition, UVA-induced enhanced expression of p53, a hallmark of UV-induced DNA damage and cell death, was also significantly inhibited by pretreatment with asiatic acid or ursolic acid. Taken together, these results suggest that asiatic acid and ursolic acid may be an effective inhibitor of UVA-modulated signal transduction pathways in human skin cells. These results further suggest that these agents may be useful in the prevention of UVA-induced photoaging. (C) 2003 Elsevier B.V. All rights reserved.