Oral Feeding of Pomegranate Fruit Extract Inhibits Early Biomarkers of UVB Radiation-Induced Carcinogenesis in SKH-1 Hairless Mouse Epidermis

摘要

Pomegranate from the plant Punica granatum possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited ultraviolet B (UVB)-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases (MAPK) pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ/cm²) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (i) skin edema, (ii) hyperplasia, (iii) infiltration of leukocytes, (iv) lipid peroxidation, (v) hydrogen peroxide generation, (vi) ODC activity, and (vii) ODC, COX-2 and PCNA protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (i) nuclear translocation of NF-κB, (ii) activation of IKKα, and (iii) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.