Isoflavones derived from many edible plants have been reported to possess significant antioxidant, estrogenic and tyrosine kinase inhibitory activity. Genistein has been found previously to provide protection from oxidative damage induced by UV radiation both in vitro and following dietary administration. We have therefore examined the potential of a number of isoflavones from red clover (Trifolium pratense) and some metabolically related compounds to offer protection from UV irradiation in hairless mice by topical application after UV exposure. We show that whereas the primary isoflavones, daidzein, biochanin A and formononetin, were inactive, 20 microM lotions of genistein and the metabolites equol, isoequol and the related derivative dehydroequol had powerful potential to reduce the inflammatory edema reaction and the suppression of contact hypersensitivity induced by moderate doses of solar-simulated UV radiation. For equol the protection was concentration dependent and 5 microM equol markedly reduced the UV-induced inflammation but abrogated the UV-induced immunosuppression. Equol protected similarly from immunosuppression induced by the putative epidermal mediator, cis-urocanic acid (UCA), indicating a potential mechanism of action involving inactivation of this UV-photoproduct. Since immunosuppression induced by both UV radiation and by cis-UCA appears to be an oxidant-dependent response our observations support the actions of these topically applied isoflavones and their metabolites as antioxidants. They also indicate that lotions containing equol, unlike topical UV sunscreens, more readily protect the immune system from photosuppression than from the inflammation of the sunburn reaction, even when applied after exposure, and thus such compounds may have a future role as sun-protective cosmetic ingredients.

Ultraviolet radiation is the most common environmental carcinogen humans are exposed to. It is now known that in order for skin cancers to develop, both genetic damage and immunosuppression is required. Ultraviolet-induced immunosuppression is therefore a key contributor to the development of skin cancer. Little is known about the relative contributions of the different ultraviolet spectra (A and B), however. Therefore detailed ultraviolet dose-response curves for systemic suppression of contact hypersensitivity in two mouse strains were determined to examine the relative contributions of each of these spectral components of sunlight to primary and secondary immunity. Whereas ultraviolet B caused a linear dose-related immunosuppression in both C57BL/6 and Balb/c mice, only C57BL/6 mice were immunosuppressed by medium doses of ultraviolet A. At higher ultraviolet A doses, C57BL/6 mice were protected from immunosuppression, suggesting a genetic predisposition to ultraviolet-A-induced immunomodulation. Surprisingly, we found that, in contrast to primary immunosuppression, low dose ultraviolet A enhanced the secondary immune response, whereas ultraviolet B caused antigen-specific tolerance. When ultraviolet A and ultraviolet B were combined to mimic sunlight (solar-simulated ultraviolet), immunosuppression and tolerance were only observed over a narrow dose range as the memory-enhancing effect of low dose ultraviolet A and the immunoprotective effect of higher dose ultraviolet A prevented the suppressive effects of ultraviolet B. These studies suggest that complex relationships between ultraviolet dose, immunomodulation, spectra, and genetic background are likely to be important for skin cancer induction. We also describe for the first time that low doses of ultraviolet A are able to enhance secondary immunity, which has important implications for vaccination strategies.

Isoflavones derived from many edible plants have been reported to possess significant antioxidant, estrogenic and tyrosine kinase inhibitory activity. Genistein has been found previously to provide protection from oxidative damage induced by UV radiation both in vitro and following dietary administration. We have therefore examined the potential of a number of isoflavones from red clover (Trifolium pratense) and some metabolically related compounds to offer protection from UV irradiation in hairless mice by topical application after UV exposure. We show that whereas the primary isoflavones, daidzein, biochanin A and formononetin, were inactive, 20 μM lotions of genistein and the metabolites equol, isoequol and the related derivative dehydroequol had powerful potential to reduce the inflammatory edema reaction and the suppression of contact hypersensitivity induced by moderate doses of solar‐simulated UV radiation. For equol the protection was concentration dependent and 5 μM equol markedly reduced the UV‐induced inflammation but abrogated the UV‐induced immunosuppression. Equol protected similarly from immunosuppression induced by the putative epidermal mediator, cis‐urocanic acid (UCA), indicating a potential mechanism of action involving inactivation of this UV‐photoproduct. Since immunosuppression induced by both UV radiation and by cis‐UCA appears to be an oxidant‐dependent response our observations support the actions of these topically applied isoflavones and their metabolites as antioxidants. They also indicate that lotions containing equol, unlike topical UV sunscreens, more readily protect the immune system from photosuppression than from the inflammation of the sunburn reaction, even when applied after exposure, and thus such compounds may have a future role as sun‐protective cosmetic ingredients.

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