title: Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice.
abstract: We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation.
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Chan Hee
authors.initials: CH
authors.lastname: Gil
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D000077407:Cilostazol; D003094:Collagen / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008812:Mice, Hairless; D023421:Models, Animal; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000032:analysis; D012867:Skin / Q000473:pathology; D015595:Skin Aging / Q000473:pathology / Q000528:radiation effects*; D013777:Tetrazoles / Q000008:administration & dosage*; D014466:Ultraviolet Rays
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D003094:Collagen; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D000077407:Cilostazol