INTRODUCTION
The number of skin cancers continues to rise, accounting for approximately 40% of all cancers reported in the United States. This results in a large expenditure of health care dollars and approximately 9,500 deaths per year.1-3 Studies have demonstrated that repeated and intense exposure to solar ultraviolet light (UV) is a major factor in human skin carcinogenesis.2-4 UV radiation is known to generate hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) free radicals, which frequently damage DNA, RNA, lipids, and proteins in human skin, resulting in skin aging and cancer.2,3,5-13
The evidence available suggests that the generation of ROS and lipid peroxidation products are important contributors responsible for changes observed during human skin aging and carcinogenesis.14,15 In addition to the exogenous generation of ROS by environmental (pollution, smoking, UV) and other factors, ROS are also byproducts of endogenous mechanisms that include normal metabolic processes, such as mitochondria-based P450 cycling, that are linked to intrinsic aging.16 ROS-induced oxidative damage to cells is often compounded over time and may be increased or reduced by a variety of factors including cellular metabolism and repair, environmental, hormonal, nutritional and toxicological contributions.17
The central role of ROS in human skin aging and carcinogenesis demonstrates the importance of developing useful anti-oxidant agents that protect skin against ROS-induced injury.8 The need for assays to quantify the anti-oxidant properties of natural products has also been highlighted, and we previously developed relevant assays in our laboratory.9,18,19 Three natural extracts that have been studied in other organ systems for their anti-oxidant properties are bisabolol, ectoin and silymarin; however, limited data is available on these compounds pertaining to their use in dermatology.
Bisabolol is a monocyclic sequiterpene alcohol extracted from chamomile and other plants.20 Ruberto et al showed that bisabolol can function as an anti-oxidant in a lipid matrix model.21 Bisabolol has been used as an anti-oxidant in gastric and hepatic models of disease and demonstrates anti-mutagenic and anti-inflammatory properties.20 Bisabolol has been evaluated in clinical studies for dermatological treatment of dyschromias and pruritus.22,23 To our knowledge no study has looked at the anti-oxidative effects of bisabolol in skin.
Silymarin is a naturally occurring product that has demonstrated anti-oxidant capabilities in human keratinocytes and murine fibroblasts.24,25 Since much of the research on silymarin evaluates individual components, a study of the anti-oxidant capabilities of unfractionated silymarin in human skin is warranted.
Flavonolignans and flavonoids, components found in silymarin, have been shown to reduce hydrogen peroxide generation in HaCaT keratinocytes and reduce H2O2-generated cytotoxicity in human keratinocytes and fibroblasts.24,25
Silymarin appears to possess several photoprotective mechanisms. In a mouse skin model, silymarin treatment caused a
