Yeom Miji, Jeon Kyungeun, Ryu De-Hun, Park Deokhoon, Jung Eunsun
Biospectrum, Life Science Institute, Yongin-Si, Republic of Korea.
PLoS One. 2025 Mar 18;20(3):e0318360. doi: 10.1371/journal.pone.0318360. eCollection 2025.
The skin serves as an essential barrier against pathogens and external insults, preventing moisture loss. Chronic skin conditions such as atopic dermatitis stem from impairments in skin barrier function. Circadian rhythms affect skin blood flow and barrier characteristics, which are significant for understanding atopic dermatitis. Cinnamomum cassia bark, commonly known as cinnamon, is extensively utilized in both modern and Traditional Chinese Medicine for its therapeutic properties in managing chronic diseases. This study aimed to investigate the potential use of Cinnamomum cassia bark in enhancing skin barrier function. We examined the impact of Cinnamomum cassia bark extract (CCBE) on circadian clock-mediated enhancement of the skin barrier. CCBE enhanced the expression of keratinocyte differentiation markers, including keratin 10, filaggrin, caspase 14, and calpain-1. CCBE also increased the production of hyaluronic acid protein. Additionally, CCBE improved the circadian rhythm of period circadian regulator 2 (PER2). Notably, CCBE upregulated the expression of keratinocyte differentiation markers and PER2 specifically during the morning hours. Furthermore, we discovered that siRNA-mediated PER2 knockdown diminished the increase in keratinocyte differentiation markers induced by CCBE. These findings demonstrate that CCBE can regulate the differentiation of keratinocytes in a time-of-day-dependent manner via the circadian clock. CCBE augmented phosphorylation of p38 and JNK, while the CCBE-induced enhancement in FLG expression and PER2 circadian rhythm was reduced by p38 MAPK inhibitors. These results suggest that CCBE can strengthen the skin barrier diurnally via the p38 MAPK pathway, representing a novel and more effective method for enhancing skin barrier function that accommodates daily variations in skin barrier properties.
皮肤是抵御病原体和外界侵害的重要屏障，可防止水分流失。特应性皮炎等慢性皮肤疾病源于皮肤屏障功能受损。昼夜节律影响皮肤血流和屏障特性，这对于理解特应性皮炎具有重要意义。肉桂，俗称桂皮，因其在治疗慢性病方面的药用特性，在现代医学和传统中医中都有广泛应用。本研究旨在探讨肉桂在增强皮肤屏障功能方面的潜在用途。我们研究了肉桂提取物（CCBE）对昼夜节律介导的皮肤屏障增强作用的影响。CCBE增强了角质形成细胞分化标志物的表达，包括角蛋白10、丝聚合蛋白、半胱天冬酶14和钙蛋白酶-1。CCBE还增加了透明质酸蛋白的产生。此外，CCBE改善了周期昼夜调节因子2（PER2）的昼夜节律。值得注意的是，CCBE在早晨时段特异性地上调了角质形成细胞分化标志物和PER2的表达。此外，我们发现siRNA介导的PER2敲低减少了CCBE诱导的角质形成细胞分化标志物的增加。这些发现表明，CCBE可通过昼夜节律以时间依赖性方式调节角质形成细胞的分化。CCBE增强了p38和JNK的磷酸化，而p38 MAPK抑制剂降低了CCBE诱导的FLG表达增强和PER2昼夜节律。这些结果表明，CCBE可通过p38 MAPK途径在白天增强皮肤屏障，这代表了一种适应皮肤屏障特性每日变化的增强皮肤屏障功能的新颖且更有效的方法。
