Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, China.
J Photochem Photobiol B. 2021 Mar;216:112147. doi: 10.1016/j.jphotobiol.2021.112147. Epub 2021 Jan 31.
Ultraviolet B (UVB) from the sunlight is a major environmental cause for human skin damages, inducing cell death, inflammation, senescence and even carcinogenesis. The natural flavonoid silibinin, clinically used as liver protectant, has protective effects against UVB-caused skin injury in vivo and in vitro. Silibinin is often classified as a phytoestrogen, because it modulates the activation of estrogen receptors (ERs). However, whether silibinin's estrogenic effect contributes to the skin protection against UVB injury remains to be elucidated. The issue was explored in this study by using the human foreskin dermal fibroblasts (HFF) and human non-malignant immortalized keratinocytes (HaCaT). In HFF, pre-treatment with silibinin rescued UVB-irradiated cells from apoptosis. Interestingly, silibinin increased the whole cellular and nuclear levels of ERα and ERβ in UVB-irradiated cells. Activation of ERs by treatment with estradiol elevated the cell survival and reduced apoptosis in UVB-treated cells. ERα agonist increased cell survival, while its antagonist decreased it. ERβ agonist also increased cell survival, but the antagonist had no effect on cell survival. Transfection of the cells with the small interfering RNAs (si-RNAs) to ERα or ERβ diminished the protective effect of silibinin on UVB-irradiated cells. In UVB-treated HaCaT cells, both ERα and ERβ were increased by silibinin treatment. Inhibition of activation and expression of ERα or ERβ by specific antagonists and si-RNAs, respectively, reduced cell survival in UVB-treated HaCaT cells regardless of silibinin treatment. Taken together, it is summarized that silibinin up-regulates both ERα and ERβ pathways in UVB-treated dermal HFF cells and epidermal HaCaT cells, leading to protection of skin from UVB-damage.
阳光中的紫外线 B（UVB）是导致人类皮肤损伤的主要环境因素，可诱导细胞死亡、炎症、衰老甚至癌变。临床上用作肝脏保护剂的天然类黄酮水飞蓟素对体内和体外 UVB 引起的皮肤损伤具有保护作用。水飞蓟素通常被归类为植物雌激素，因为它可以调节雌激素受体（ERs）的激活。然而，水飞蓟素的雌激素作用是否有助于皮肤免受 UVB 损伤仍有待阐明。本研究通过人包皮真皮成纤维细胞（HFF）和人非恶性永生化角质形成细胞（HaCaT）探讨了这一问题。在 HFF 中，水飞蓟素预处理可挽救 UVB 照射的细胞免于凋亡。有趣的是，水飞蓟素增加了 UVB 照射细胞的整个细胞和核 ERα 和 ERβ 水平。用雌二醇处理激活 ERs 可提高 UVB 处理细胞的细胞存活率并减少凋亡。ERα 激动剂增加细胞存活率，而其拮抗剂则降低细胞存活率。ERβ 激动剂也增加了细胞存活率，但拮抗剂对细胞存活率没有影响。用 ERα 或 ERβ 的小干扰 RNA（si-RNA）转染细胞可降低水飞蓟素对 UVB 照射细胞的保护作用。在 UVB 处理的 HaCaT 细胞中，水飞蓟素处理均可增加 ERα 和 ERβ。分别用特异性拮抗剂和 si-RNA 抑制 ERα 或 ERβ 的激活和表达，可降低 UVB 处理的 HaCaT 细胞的细胞存活率，而与水飞蓟素处理无关。综上所述，水飞蓟素可上调 UVB 处理的真皮 HFF 细胞和表皮 HaCaT 细胞中的 ERα 和 ERβ 通路，从而保护皮肤免受 UVB 损伤。
