Triazole 衍生物(3-PED4HPT)之抗光老化研究

Abstract

In our daily lives, we will be exposed to the UV light from the sun. The skin acts as an important physiological barrier for our body, it protects us from chemical and physical damages. The skin will show wrinkles or signs of photoaging after ultraviolet (UV) radiation exposure. It has become apparent that chronic UV exposure not only accelerates the aging process, but also accumulates the risk of skin carcinogenesis. UVA wavelength is between 320nm to 400nm. At this wavelength, it makes it is possible for UV radiation penetrate our skin and reach the dermis layer of skin. It damages the normal skin structure by generating ROS, which will damage DNA and activate the matrix metalloproteinase-1 (MMP-1). MMP-1 is responsible for the degradation of collagen and photoaging. Triazole has been reported that to have antibacterial, antiallergic, anti-HIV abilities. Furthermore, in our study, we found that Triazole derivative compounds (3-PED4HPT) have anti-photoaging effects in UVA-irradiated human fibroblasts. Two Triazole derivative compounds, SM-72-Ph and 1-YNE-3-Ph, have much better anti-photoaging activity than other derivatives. Our data shows that SM-72-Ph and 1-YNE-3-Ph can suppress UVA-induced damage in human skin fibroblasts, cause a decrease in matrix metalloproteinase-1 (MMP-1) expression, reduce reactive oxygen species (ROS) generation, increase COL1α1 and TIMP-1(inhibitor of MMP-1), and maintain the mitochondrial membrane potential (Δ?卌t). In animal experiment, epidermal thickness is used as a parameter to reflect skin photoaging quantitatively, since epidermal hypertrophy is thought to cause wrinkle formation. In our study, the epidermal thickness of the mice dorsal skin was significantly increased by chronic UVA exposure. The epidermal hypertrophy was significantly reduced by topical application of SM-72-Ph. In vivo data also show that SM-72-Ph can reduce epidermal thickness of the dorsal skin of the mice. Thus, we suggest 3-PED4HPT as potential anti-photoaging agents.