title: The novel PPAR α/γ dual agonist MHY 966 modulates UVB-induced skin inflammation by inhibiting NF-κB activity.
abstract: Ultraviolet B (UVB; 290~320nm) irradiation-induced lipid peroxidation induces inflammatory responses that lead to skin wrinkle formation and epidermal thickening. Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have the potential to be used as anti-wrinkle agents because they inhibit inflammatory response and lipid peroxidation. In this study, we evaluated the function of 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl) phenol (MHY 966), a novel synthetic PPAR α/γ dual agonist, and investigated its anti-inflammatory and anti-lipid peroxidation effects. The action of MHY 966 as a PPAR α/γ dual agonist was also determined in vitro by reporter gene assay. Additionally, 8-week-old melanin-possessing hairless mice 2 (HRM2) were exposed to 150 mJ/cm(2) UVB every other day for 17 days and MHY 966 was simultaneously pre-treated every day for 17 days to investigate the molecular mechanisms involved. MHY 966 was found to stimulate the transcriptional activities of both PPAR α and γ. In HRM2 mice, we found that the skins of mice exposed to UVB showed significantly increased pro-inflammatory mediator levels (NF-κB, iNOS, and COX-2) and increased lipid peroxidation, whereas MHY 966 co-treatment down-regulated these effects of UVB by activating PPAR α and γ. Thus, the present study shows that MHY 966 exhibits beneficial effects on inflammatory responses and lipid peroxidation by simultaneously activating PPAR α and γ. The major finding of this study is that MHY 966 demonstrates potential as an agent against wrinkle formation associated with chronic UVB exposure.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Korea ; Laboratory of Biochemistry, Pusan National University, Busan, Korea.
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jeong
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Kim
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D052160:Benzothiazoles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011487:Protein Conformation; D059748:Proteolysis / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000893:Anti-Inflammatory Agents; D052160:Benzothiazoles; C580737:MHY966; D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D010636:Phenols; D030421:Peroxynitrous Acid; D003094:Collagen