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 10 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 approximately 60% decrease (P < 0.001) in neutrophil infiltration at 24 hours, and macrophages by approximately 50% (<0.02) at 24 and 48 hours. By 72 hours, 54 +/- 5% cyclobutane pyrimidine dimers remained in vehicle-fed 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 approximately 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 approximately 59% (P < 0.01) and approximately 79% (P < 0.03) lower in PL-fed versus vehicle-fed mice. Finally, UV-induced mutations in PL-fed-mice were decreased by approximately 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.
Zattra
Edoardo
E
Department of Dermatology, Boston University School of Medicine, MA 02118, USA.
Coleman
Christina
C
Arad
Simin
S
Helms
Elizabeth
E
Levine
Danielle
D
Bord
Evelyn
E
Guillaume
Alexandra
A
El-Hajahmad
Mohamad
M
Zwart
Edwin
E
van Steeg
Harry
H
Gonzalez
Salvador
S
Kishore
Raj
R
Goukassian
David A
DA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019587:Dietary Supplements; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D016296:Mutagenesis / Q000187:drug effects / Q000528:radiation effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D032494:Polypodium / Q000737:chemistry*; D011740:Pyrimidine Dimers / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D010936:Plant Extracts; D011740:Pyrimidine Dimers; D016159:Tumor Suppressor Protein p53; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051546:Cyclooxygenase 2; D003849:Deoxyguanosine