Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
J Dermatol Sci. 2018 May;90(2):123-134. doi: 10.1016/j.jdermsci.2018.01.004. Epub 2018 Feb 1.
UVA irradiation-induced skin damage/photoaging is associated with redox imbalance and collagen degradation.
Dermato-protective efficacies of trans-cinnamic acid (t-CA), a naturally occurring aromatic compound have been investigated against UVA irradiation, and elucidated underlying molecular mechanism.
Human foreskin fibroblast-derived (Hs68) cells and nude mice were treated with t-CA prior to UVA exposure, and assayed the anti-photoaging effects of t-CA.
We found t-CA (20-100 μM) pretreatment substantially ameliorated UVA (3 J/cm)-induced cytotoxicity, and inhibited intracellular ROS production in Hs68 cells. UVA-induced profound upregulation of metalloproteinase (MMP)-1/-3 and degradation of type I procollagen in dermal fibroblasts were remarkably reversed by t-CA, possibly through inhibition of AP-1 (c-Fos, but not c-Jun) translocation. The t-CA-mediated anti-photoaging properties are associated with increased nuclear translocation of Nrf2. Activation of Nrf2 signaling is accompanied with induction of HO-1 and γ-GCLC expressions in t-CA-treated fibroblasts. Furthermore t-CA-induced Nrf2 translocation is mediated through PKC, AMPK, CKII or ROS signaling cascades. This phenomenon was confirmed with respective pharmacological inhibitors, GF109203X, Compound C, CKII inhibitor or NAC, which blockade t-CA-induced Nrf2 activation. Silencing of Nrf2 signaling with siRNA showed no anti-photoaging effects of t-CA against UVA-induced ROS production, loss of HO-1 and type I collagen degradation in fibroblasts. In vivo evidence on nude mice revealed that t-CA pretreatment (20 or 100 mM/day) significantly suppressed MMP-1/-3 activation and maintained sufficient type I procollagen levels in biopsied skin tissue against UVA irradiation (3 J/cm/day for 10-day).
t-CA treatment diminished UVA-induced photoaging/collagen degradation, and protected structural integrity of the skin.
UVA 照射引起的皮肤损伤/光老化与氧化还原失衡和胶原蛋白降解有关。
本研究旨在探讨肉桂酸（t-CA）作为一种天然芳香族化合物对 UVA 照射的皮肤保护作用，并阐明其潜在的分子机制。
用 t-CA 预处理人包皮成纤维细胞（Hs68）和裸鼠，然后检测 t-CA 的抗光老化作用。
我们发现，t-CA（20-100μM）预处理可显著改善 UVA（3J/cm）照射引起的细胞毒性，并抑制 Hs68 细胞内 ROS 的产生。UVA 诱导真皮成纤维细胞中基质金属蛋白酶（MMP）-1/-3 的显著上调和 I 型前胶原的降解被 t-CA 显著逆转，这可能是通过抑制 AP-1（c-Fos，但不是 c-Jun）易位。t-CA 介导的抗光老化特性与 Nrf2 的核易位增加有关。在 t-CA 处理的成纤维细胞中，Nrf2 信号的激活伴随着 HO-1 和γ-GCLC 表达的诱导。此外，t-CA 诱导的 Nrf2 易位是通过 PKC、AMPK、CKII 或 ROS 信号级联介导的。这一现象被各自的药理学抑制剂 GF109203X、Compound C、CKII 抑制剂或 NAC 所证实，这些抑制剂阻断了 t-CA 诱导的 Nrf2 激活。用 siRNA 沉默 Nrf2 信号后，t-CA 对 UVA 诱导的 ROS 产生、HO-1 和 I 型胶原蛋白降解无抗光老化作用。裸鼠体内实验结果表明，t-CA 预处理（20 或 100mM/天）可显著抑制 MMP-1/-3 的激活，并维持 UVA 照射（每天 3J/cm，共 10 天）后活检皮肤组织中 I 型前胶原的水平。
t-CA 治疗可减轻 UVA 诱导的光老化/胶原蛋白降解，保护皮肤结构的完整性。
