Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

Po-Yuan Wu,Jia-Ling Lyu,Hao-Cheng Hsu,Ting-Yi Chien,Yi-Jung Liu,Hsiu-Mei Chiang,Kuo-Ching Wen

doi:10.3390/ijms18102118

Abstract

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin’s antiphotodamage and antiphotoinflammation activities.

Highlights

The skin is an external organ that acts as a crucial barrier and defense system to prevent water loss and damage due to sunlight exposure and environmental pollution
The topical application of fisetin alleviated Transepidermal water loss (TEWL) induced by ultraviolet B (UVB) exposure (Figure 1), indicating that fisetin maintained skin barrier function during UVB exposure
A previous study demonstrated that fisetin protects the skin from UVB-induced damage by inhibiting reactive oxygen species (ROS) generation and the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1)/matrix metalloproteinases (MMPs) signaling pathway, decreasing collagen degradation in UV irradiation enhances ROS formation to disturb the balance between the synthesis and degradation of collagen

Summary

Introduction

The skin is an external organ that acts as a crucial barrier and defense system to prevent water loss and damage due to sunlight exposure and environmental pollution. Ultraviolet (UV) irradiation induces reactive oxygen species (ROS) generation and inflammation in the dermis [1,2]. Long-term UV exposure causes skin sagging or wrinkle formation because of the degradation of extracellular matrix (ECM) proteins, including elastin, collagen, and fibronectin [3]. Collagen is the main structural protein in the dermis and is synthesized in fibroblasts. UV irradiation activates the signaling transduction pathway related to collagen degradation, causing the aforementioned fragmentation of collagen fibers that leads to skin sagging and wrinkle formation. UV-induced MMP activation triggers ECM ubiquitination, which causes skin damage and wrinkle formation [4,5]

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Discussion

Conclusion