Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin.

Abstract

Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2'-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways.

• Authors: Poyil Pratheeshkumar, Young-Ok Son, Xin Wang, Sasidharan Padmaja Divya, Binoy Joseph, John Andrew Hitron, Lei Wang, Donghern Kim, Yuanqin Yin, Ram Vinod Roy, Jian Lu, Zhuo Zhang, Yitao Wang, Xianglin Shi
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 280 Issue 1 Pg. 127-37 (Oct 01 2014) ISSN: 1096-0333 [Electronic] United States
• PMID: 25062774 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Anthocyanins
• Glucosides
• NF-kappa B
• cyanidin-3-O-beta-glucopyranoside
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Anthocyanins (pharmacology)
• Dose-Response Relationship, Drug
• Female
• Glucosides (pharmacology)
• Inflammation (metabolism, pathology, prevention & control)
• Mice
• Mice, Hairless
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, physiology)
• NF-kappa B (antagonists & inhibitors, physiology)
• Oxidative Stress (drug effects, physiology, radiation effects)
• Random Allocation
• Signal Transduction (drug effects, physiology, radiation effects)
• Skin Absorption (drug effects, physiology, radiation effects)
• Ultraviolet Rays (adverse effects)