There are several theories on photoaging and its etiology. At this time, however, the only defenses commonly believed to prevent photoaging are the use of sunscreens to reduce the amount of ultraviolet (UV) that reaches the skin, the use of retinoids to prevent production of collagenase and stimulate collagen production, and the use of antioxidants to reduce and neutralize free radicals. The Pinnell paper in this issue of the Journal of Investigative Dermatology that examines ferulic acid combined with vitamins C and E shows that this formulation seems to provide two of the above defenses: a sunscreen effect, and an antioxidant effect. Not all sunscreens confer an antioxidant effect and not all antioxidants yield a sunscreen effect (Pinnell et al, 2005b). For example, Kang et al (2003) showed that although genistein and Nacetyl cysteine exhibit antioxidant activity, they produced no effect on ultraviolet-induced erythema. UV exposure results in skin damage through several mechanisms including sunburn cell development, thymine dimer formation, collagenase production, and the provocation of an inflammatory response. Sunburn cells, or UV-induced apoptotic cells, have long been used to assess skin damage due to ultraviolet exposure. UV-induced apoptosis is mediated by caspase-3 (Lin et al, 2005). Activation occurs in a pathway that involves caspase-7 (Pinnell et al, 2005a). It is believed that capsase-3 levels are good indicators of the presence of cellular apotosis (Kang et al, 2003; Philips et al, 2003; Lin et al, 2005; Yao et al, 2005). Theoretically, the fewer sunburn cells present, less the ‘‘skin damage’’ from UV exposure. At this time, sun avoidance and use of sunscreens are the only defenses against sunburn cell formation. Sunscreens and sun avoidance can also protect against thymine dimer formation. Antioxidants protect the skin from free radicals through several mechanisms in the early stages of elucidation. Free radicals can act directly on growth factors and cytokine receptors in keratinocytes and dermal cells, leading to skin inflammation. Kang et al have shown that free radical activation of the mitogen-activated protein (MAP) kinase pathways results in production of collagenase, which leads to degradation of collagen (Saliou et al, 2001; Greul et al, 2002; Kang et al, 2003; Papucci et al, 2003; Passi et al, 2003; Middelkamp-Hup et al, 2004a, b; Sime and Reeve, 2004; Katiyar, 2005). Blocking these pathways with antioxidants is thought to prevent photoaging by preventing the production of collagenase. This theory has been buttressed by research on human skin performed by Kang et al. In this study, investigators showed that when human skin was pretreated with the antioxidants genistein and N-acetyl cysteine, the UV induction of the cJun-driven enzyme collagenase was inhibited. Many antioxidants are now available in oral and topical preparations. Studies such as the one by Pinnell suggest that combinations of various antioxidants may have synergistic effects, yielding formulations with greater efficacy than any of the individual antioxidant compounds used alone. Each antioxidant is endowed with various properties that distinguish it from other antioxidants. Some examples of popular antioxidants and their characteristics will be briefly discussed. Pycnogenol is a trademark name for a standardized extract of the bark of the French maritime pine plant, which is rich in procyanidins, also called proanthocyanidins. These potent free-radical scavengers can also be found in grape seed, grape skin, bilberry, cranberry, black currant, green tea, black tea, blueberry, blackberry, strawberry, black cherry, red wine, and red cabbage. In one study (Sime and Reeve, 2004), Pycnogenol concentrations of 0.05%– 0.2% were applied to the irradiated dorsal skin of Skh:hr hairless mice exposed daily to minimally inflammatory solarsimulated UV radiation. Mice pretreated with Pycnogenol demonstrated a concentration-dependent reduction of the inflammatory sunburn reaction (edema). In a study (Saliou et al, 2001) evaluating the capacity of pine bark extract to protect human skin against erythema induced by solar radiation, 21 volunteers received oral supplementation of Pycnogenol. During supplementation, the UVR level necessary to reach one minimal erythema dose (MED) was significantly elevated, suggesting that oral pine bark extract supplementation mitigates the effects of UV radiation on the skin, lowering erythema. The mechanism of action of Pycnogenol may transcend its free-radical scavenging activities, as suggested by its anti-inflammatory effects, which are partially ascribed to the fact that Pycnogenol inhibits IFN-g-induced expression of ICAM-1 (Bito et al, 2000). Silymarin is a naturally occurring polyphenolic flavonoid compound or flavonolignans antioxidant derived from the seeds of the milk thistle plant Silybum marianu. The beneficial effects of silymarin are primarily the result of its main active constituent silybin, which was shown to be bioavailable in the skin and other tissues following systemic administration (Zhao and Agarwal, 1999). Topical application of silybin before or immediately after UV irradiation has been found to impart strong protection against UV-induced damAbbreviations: CoQ10, coenzyme Q10; UV, ultraviolet
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Feb 1, 2023
Mo-Yi Yue + 4
Open Access