Anethole prevents hydrogen peroxide-induced apoptosis and collagen metabolism alterations in human skin fibroblasts

The collagen metabolism alterations triggered by reactive oxygen species are involved in the development of various connective tissue diseases and skin aging. This study was designed to examine whether (E)-anethole possesses a protective effect on H(2)O(2)-induced alterations in collagen metabolism as well as whether it can prevent apoptosis in human skin fibroblasts. In cells treated with 300 µM H(2)O(2), a decrease in collagen biosynthesis of 54 % was observed. Pretreatment of cells with 0.5 µM anethole for 1 h completely prevented this alteration. Changes at the protein level positively correlated with alterations of type I collagen mRNA expression. We have shown that H(2)O(2) caused increase in the activity of MMP-2 and MMP-9 as well as that an increase in MMP-2 activity can contribute to the 8 % decrease in the amount of collagen secreted into the medium. The most efficient suppression of these changes was observed in the presence of 0.5 µM of anethole. At 10 µM, in addition to suppression, an inhibitory effect of anethole on MMP-9 activity was documented. Additionally, the 60 % H(2)O(2)-induced decrease in cell viability was suppressed by 1 µM of anethole and a 4-fold increase in cell apoptosis was suppressed by 0.5 µM of anethole. Our results suggest that anethole, which is a small lipophilic and non-toxic molecule with the ability to prevent H(2)O(2)-induced collagen metabolism alterations and apoptosis in human skin fibroblasts, would prove useful in the development of effective agents in pharmacotherapy of oxidative stress-related skin diseases.