Abstract

Excessive exposure to solar UV (sUV) is associated with numerous human skin disorders, such as carcinogenesis, skin photoaging and skin inflammation. Silkworm Thorn (Cudraniatricuspidata, SW) is a plant belonging to the Moraceae family and widely present throughout Korea, China, and Japan. Most parts of the tree (including the fruit, leaf, stem, root, and bark) is consumable as a functional food or tea. In this study, we found that SW extract (SWE) inhibited the elevated expression of sUV-induced cyclooxygenase (COX)-2 levels in both HaCaT and JB6 cells. Levels of nuclear factor-κB and activator protein-1, two crucial transcription factors involved in COX-2 expression, were elevated by sUV treatment. Treatment with SWE abolished this activation. SWE also inhibited sUV-induced histone H3 phosphorylation. However, sUV-induced phosphorylation of Akt, c-Jun N-terminal kinase and p38 kinase remained unchanged in the presence of SWE. SWE inhibited RSK2 activity, and pull-down assays using SWE-Sepharose beads revealed that SWE binds directly with RSK2 in an ATP-competitive manner. These results suggest a potential for SWE to be developed as a cosmeceutical material and functional food constituent for the promotion of skin health.

Highlights

  • Ultraviolet (UV) is a major etiological factor involved in skin photoaging and carcinogenesis [1].Exposure of the skin to UV induces damage of DNA, protein, and lipids, which can in turn lead to skin inflammation, a process that precedes photoaging and carcinogenesis [2]

  • To measure whether COX-2 inhibition by SW extract (SWE) through transcriptional regulation, we showed the effects of SWE on Solar UV (sUV)-induced cox-2 promoter activity

  • Luciferase assays revealed that exposure to sUV induced cox-2 promoter activity significantly and this induction was suppressed by SWE treatment (Figure 1C)

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Summary

Introduction

Ultraviolet (UV) is a major etiological factor involved in skin photoaging and carcinogenesis [1]. Exposure of the skin to UV induces damage of DNA, protein, and lipids, which can in turn lead to skin inflammation, a process that precedes photoaging and carcinogenesis [2]. Methods to inhibit sUV-induced skin inflammation may help to counteract these adverse effects. The effects of SW on sUV-induced skin inflammation have not previously been investigated. Cyclooxygenase (COX)-2 plays a crucial role in sUV-induced skin inflammation [14]. COX-2 expression and COX-2-mediated sUV-induced skin inflammation [17]. We investigated the inhibitory effects of SW extract (SWE) on sUV-induced COX-2 expression in skin cells

SWE Inhibits sUV-Induced COX-2 Expression through Transcriptional Suppression
SWE Does Not Inhibit sUV-Induced MAPK or Akt Signaling Activity
SWE Inhibits RSK2 Activity though Direct Binding
Discussion
Materials
Cell Culture and sUV Radiation
Western Blot Analysis
Cell Viability
In Vitro RSK2 Kinase Assay
SWE Pull-down Assay
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