Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin

Toxicol Appl Pharmacol. 2015 Apr 1;284(1):92-99. doi: 10.1016/j.taap.2015.02.003. Epub 2015 Feb 11.


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.

Keywords: Blackberry extract; COX-2; Inflammation; NF-κB; Ultraviolet radiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Biomarkers / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects
  • DNA Damage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Fruit
  • Inflammation Mediators / metabolism
  • Lipid Peroxidation / drug effects
  • Mice, Hairless
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasms, Radiation-Induced / enzymology
  • Neoplasms, Radiation-Induced / immunology
  • Neoplasms, Radiation-Induced / prevention & control
  • Oxidative Stress / drug effects*
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Rubus* / chemistry
  • Signal Transduction / drug effects*
  • Skin / drug effects*
  • Skin / enzymology
  • Skin / immunology
  • Skin / pathology
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / immunology
  • Skin Neoplasms / prevention & control
  • Sunburn / enzymology
  • Sunburn / immunology
  • Sunburn / pathology
  • Sunburn / prevention & control*
  • Sunscreening Agents / isolation & purification
  • Sunscreening Agents / pharmacology*
  • Time Factors
  • Ultraviolet Rays*


  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • Cell Cycle Proteins
  • Inflammation Mediators
  • NF-kappa B
  • Plant Extracts
  • Sunscreening Agents
  • Mitogen-Activated Protein Kinases