Baicalin Protects Keratinocytes from Toll‐like Receptor‐4 Mediated DNA Damage and Inflammation Following Ultraviolet Irradiation. (11th September 2015)

• Record Type: Journal Article
• Authors: Min, Wei; Ahmad, Israr; Chang, Michelle E.; Burns, Erin M.; Qian, Qihong; Yusuf, Nabiha
• Is Part Of: Photochemistry and photobiology. Volume 91:Number 6(2015:Nov./Dec.)
• Page Start: 1435
• Page End: 1443
• Publication Date: 2015-09-11
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.12505
• Languages: English
• ISSNs: 0031-8655

Abstract

Abstract: UVB radiation contributes to both direct and indirect damage to the skin including the generation of free radicals and reactive oxygen species (ROS), inflammatory responses, immunosuppression and gene mutations, which can ultimately lead to photocarcinogenesis. A plant‐derived flavonoid, baicalin, has been shown to have antioxidant, anti‐inflammatory and free radical scavenging activities. Previous studies from our laboratory have shown that in murine skin, Toll‐like receptor‐4 (TLR4) enhanced both UVB‐induced DNA damage and inflammation. The aim of this study was to investigate the efficacy of baicalin against TLR4‐mediated processes in the murine keratinocyte PAM 212 cell line. Our results demonstrate that treating keratinocytes with baicalin both before and after UV radiation (100 mJ cm −2 ) significantly inhibited the level of intracellular ROS and decreased cyclobutane pyrimidine dimers and 8‐Oxo‐2′‐deoxyguanosine (8‐oxo‐dG)—markers of DNA damage. Furthermore, cells treated with baicalin demonstrated an inhibition of TLR4 and its downstream signaling molecules, MyD88, TRIF, TRAF6 and IRAK4. TLR4 pathway inhibition resulted in NF‐ κ B inactivation and down‐regulation of iNOS and COX‐2 protein expression. Taken together, baicalin treatment effectively protected keratinocytes from UVB‐induced inflammatory damage through TLR pathway modulation. Abstract : UVB radiation causes both direct and indirect damage to the skin including the generation of reactive oxygen species (ROS), inflammation and immunosuppression, which ultimately contribute to photocarcinogenesis. A plant‐derived flavonoid, baicalin, has been shown to be effective as an antioxidant, anti‐inflammatory and free radical scavenger. Baicalin treatment before and after UV radiation protected PAM212 keratinocytes from UVB‐induced damage by inhibiting Toll‐like receptor‐4 (TLR4) and its downstream signaling molecules, MyD88, TRIF, TRAF6 and IRAK4. This inhibition resulted in NF‐ κ B inactivation and downregulation of iNOS and COX‐2. Intracellular ROS and markers of DNA damage, including cyclobutane pyrimidine dimers and 8‐Oxo‐2′‐deoxyguanosine, were significantly reduced.