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.

Ganoderma lucidum polysaccharide inhibits UVB‐induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways

“…UV‐induced ROS plays an important role in activating melanogenesis mediated by the MAPK signaling pathway (H.N. Kim, Gil, Kim, Shin, & Choi, ). Our preliminary study has also demonstrated that ROS inhibitor NAC can antagonize UVB‐induced activation of MAPK signaling pathway in melanocytes (Zeng et al, ).…”

Decanal Protects against UVB-Induced Photoaging in Human Dermal Fibroblasts via the cAMP Pathway

“…Similarly, a cAMP increase, triggered by the activation of a specific G-protein-coupled receptor (GPCR; an adenosine A2A receptor, upstream of Adcy), inhibits the MMP pathway, thus stimulating collagen production in human dermal fibroblasts [10]. Topical cilostazol (cAMP phosphodiesterase inhibitor) application protects against UVB-mediated MMP expression and subsequent photoaging, including wrinkle formation in the skin of hairless mice, through cAMP-dependent intracellular signaling [11].…”

Laminarin Attenuates Ultraviolet-Induced Skin Damage by Reducing Superoxide Anion Levels and Increasing Endogenous Antioxidants in the Dorsal Skin of Mice

“…To examine changes in the epithermal thickness and density of collagen fibers in the dermis in the dorsal skin, the tissue sections were stained with Masson's trichrome staining kit (Abcam, Cambridge, MA, USA), as described by Kim et al [44] The stained sections were prepared as permeant slides. Five sections per each animal were randomly selected to analyze epithermal thickness and the density of collagen fibers.…”