title: 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: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA; Graduate Center for Toxicology, 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; Graduate Center for Toxicology, 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; Graduate Center for Toxicology, 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; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Sasidharan Padmaja
authors: SP
authors: Divya
authors: Spinal Cord and Brain Injury Research Center and Department of Physiology, University of Kentucky, Lexington, KY 40536-0509, USA.
authors: Binoy
authors: B
authors: Joseph
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA; Graduate Center for Toxicology, 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; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Lei
authors: L
authors: Wang
authors: Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Donghern
authors: D
authors: Kim
authors: Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA; Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Yuanqin
authors: Y
authors: Yin
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Ram Vinod
authors: RV
authors: Roy
authors: Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Jian
authors: J
authors: Lu
authors: Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA.
authors: Zhuo
authors: Z
authors: Zhang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors: Yitao
authors: Y
authors: Wang
authors: Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536, USA. Electronic address: xshi5@email.uky.edu.
authors: Xianglin
authors: X
authors: Shi
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008812:Mice, Hairless; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D016328:NF-kappa B; C462279:cyanidin-3-O-beta-glucopyranoside; D020928:Mitogen-Activated Protein Kinases
keywords: COX-2; Cyanidin-3-glucoside; Inflammation; NF-κB; Ultraviolet radiation