title: Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin.
abstract: Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100 mJ/cm(2)) on alternate days for 10 weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasia and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. Likewise, UVB-induced inflammatory responses were diminished by BBE as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, BBE also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) levels in UVB-exposed skin. Treatment with BBE inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mouse skin. Immunohistochemistry analysis revealed that topical application of BBE inhibited the expression of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG), cyclobutane pyrimidine dimers (CPD), proliferating cell nuclear antigen (PCNA), and cyclin D1 in UVB-exposed skin. Collectively, these data indicate that BBE protects from UVB-induced oxidative damage and inflammation by modulating MAP kinase and NF-κB signaling pathways.
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Sasidharan Padmaja
authors: SP
authors: Divya
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Xin
authors: X
authors: Wang
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Poyil
authors: P
authors: Pratheeshkumar
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Young-Ok
authors: YO
authors: Son
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Ram Vinod
authors: RV
authors: Roy
authors: Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Donghern
authors: D
authors: Kim
authors: Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Jin
authors: J
authors: Dai
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: John Andrew
authors: JA
authors: Hitron
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Lei
authors: L
authors: Wang
authors: National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin, India.
authors: Padmaja
authors: P
authors: Asha
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.|Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Xianglin
authors: X
authors: Shi
authors: Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Zhuo
authors: Z
authors: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005638:Fruit; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008812:Mice, Hairless; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D065856:Rubus / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D013471:Sunburn / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013473:Sunscreening Agents / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D018797:Cell Cycle Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D010936:Plant Extracts; D013473:Sunscreening Agents; D020928:Mitogen-Activated Protein Kinases
keywords: Blackberry extract; COX-2; Inflammation; NF-κB; Ultraviolet radiation