Polypodium leucotomos Extract Decreases UV-Induced Cox-2 Expression and Inflammation, Enhances DNA Repair, and Decreases Mutagenesis in Hairless Mice

UV-irradiated skin and UV-induced tumors overexpress the inducible isoform of cyclooxygenase-2 (Cox-2), and Cox-2 inhibition reduces photocarcinogenesis. To evaluate photoprotective effects of Polypodium leucotomos extract (PL), hairless Xpc(+/-) mice were fed for 110 days with PL (300 mg/kg) or vehicle then UV-irradiated, once. By 24 hours, UV-induced Cox-2 levels were increased in vehicle-fed and PL-fed mice, whereas by 48 and 72 hours, Cox-2 levels were four- to fivefold lower in PL-fed mice (P < 0.05). P53 expression/activity was increased in PL-fed versus vehicle-fed then UV-irradiated mice. UV-induced inflammation was decreased in PL-fed mice, as shown by similar to 60% decrease (P < 0.001) in neutrophil infiltration at 24 hours, and macrophages by similar to 50% (<0.02) at 24 and 48 hours. By 72 hours, 54 +/- 5% cyclobutane pyrimidine dimers remained in vehiclefed versus 31 +/- 5% in PL-fed skin (P < 0.003). The number of 8-hydroxy-2'-deoxyguanosine-positive cells were decreased before UV irradiation by similar to 36% (P < 0.01), suggesting that PL reduces constitutive oxidative DNA damage. By 6 and 24 hours, the number of 8-hydroxy-2'-deoxyguanosine-positive cells were similar to 59% (P < 0.01) and similar to 79% (P < 0.03) lower in PL-fed versus vehicle-fed mice. Finally, UV-induced mutations in PL-fed-mice were decreased by similar to 25% when assessed 2 weeks after the single UV exposure. These data demonstrate that PL extract supplementation affords the following photoprotective effects: P53 activation and reduction of acute inflammation via Cox-2 enzyme inhibition, increased cyclobutane pyrimidine dimer removal, and reduction of oxidative DNA damage. (Am J Pathol 2009, 175:1952-1961; DOI: 10.2353/ajpath.2009.090351)