Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
School of Medicine, Sungkyunkwan University, Seoul 06351, Korea.
Mar Drugs. 2020 Jul 22;18(8):377. doi: 10.3390/md18080377.
Radiation dermatitis (RD) is one of the most common side effects of radiotherapy; its symptoms progress from erythema to dry and moist desquamation, leading to the deterioration of the patients' quality of life. Active metabolites in brown seaweed, including phlorotannins (PTNs), show anti-inflammatory activities; however, their medical use is limited. Here, we investigated the effects of PTNs in a mouse model of RD in vivo. X-rays (36 Gy) were delivered in three fractions to the hind legs of BALB/c mice. Macroscopic RD scoring revealed that PTNs significantly mitigated RD compared with the vehicle control. Histopathological analyses of skin tissues revealed that PTNs decreased epidermal and dermal thickness compared with the vehicle control. Western blotting indicated that PTNs augmented nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activation but attenuated radiation-induced NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and inflammasome activation, suggesting the mitigation of acute inflammation in irradiated mouse skin. PTNs also facilitated fast recovery, as indicated by increased aquaporin 3 expression and decreased γH2AX (histone family member X) expression. Our results indicate that topical PTN application may alleviate RD symptoms by suppressing oxidative stress and inflammatory signaling and by promoting the healing process. Therefore, PTNs may show great potential as cosmeceuticals for patients with cancer suffering from radiation-induced inflammatory side effects such as RD.
放射性皮炎（RD）是放疗最常见的副作用之一；其症状从红斑进展为干燥和湿性脱屑，导致患者生活质量恶化。褐藻中的活性代谢物，包括岩藻黄质（PTN），具有抗炎活性；然而，它们的医学用途受到限制。在这里，我们研究了 PTN 在体内 RD 小鼠模型中的作用。X 射线（36 Gy）分 3 次照射 BALB/c 小鼠后腿。宏观 RD 评分显示，与载体对照组相比，PTN 显著减轻 RD。皮肤组织的组织病理学分析表明，与载体对照组相比，PTN 降低了表皮和真皮的厚度。Western blot 分析表明，PTN 增强了核因子红细胞 2 相关因子 2（NRF2）/血红素加氧酶 1（HO-1）途径的激活，但减弱了辐射诱导的 NF-κB（核因子 kappa-轻链增强子的激活 B 细胞）和炎症小体的激活，提示减轻了辐照小鼠皮肤的急性炎症。PTN 还通过增加水通道蛋白 3 的表达和减少 γH2AX（组蛋白家族成员 X）的表达促进快速恢复。我们的结果表明，局部应用 PTN 通过抑制氧化应激和炎症信号以及促进愈合过程来缓解 RD 症状。因此，PTN 可能作为治疗癌症患者因放射性炎症副作用（如 RD）而引起的炎症的美容产品具有巨大的潜力。
