The Anti-Wrinkle Mechanism of Melatonin in UVB Treated HaCaT Keratinocytes and Hairless Mice via Inhibition of ROS and Sonic Hedgehog Mediated Inflammatory Proteins

褪黑素在 UVB 处理的 HaCaT 角质形成细胞和无毛小鼠中通过抑制 ROS 和 Sonic Hedgehog 介导的炎症蛋白发挥抗皱作用的机制

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作者:Eun Kyung Park, Hyo-Jung Lee, Hyemin Lee, Ju-Ha Kim, Jisung Hwang, Ja Il Koo, Sung-Hoon Kim

Abstract

Though melatonin is known to improve ultraviolet B (UVB)-induced oxidative damage and inflammatory conditions via the blockade of the nuclear factor (NF)-κB, interleukin (IL)-6, there is no report on the anti-wrinkle effect of melatonin to date. Hence in the present study, the anti-wrinkle mechanism of melatonin was elucidated in UVB treated HaCaT keratinocytes and hairless mice. Herein melatonin protected against a radical initiator tert-Butyl hydroperoxide (t-BOOH) induced reactive oxygen species (ROS) production, matrix metalloprotease 1 (MMP-1), pro-collagen and cytotoxicity in HaCaT keratinocytes. Additionally, melatonin suppressed the expression of sonic hedgehog (SHH) and GLI1 for hedgehog signaling and p-NF-κB, cyclooxygenase (COX-2), phospho-extracellular signal-regulated kinase-1 (p-ERK) for inflammatory responses in UVB treated HaCaT keratinocytes. Furthermore, melatonin protected skin from wrinkle formation, transdermal water loss in hairless mice irradiated by UVB for 8 weeks. Notably, melatonin prevented against epidermal thickness and dermal collagen degradation in UVB irradiated hairless mice by Hematoxylin and Eosin and Masson’s trichrome staining. Taken together, these findings suggest that melatonin reduces wrinkle formation via inhibition of ROS/SHH and inflammatory proteins such as NF-κB/COX-2/ERK/MMP1.

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