Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City 33303, Taiwan.
Int Immunopharmacol. 2018 Jul;60:202-210. doi: 10.1016/j.intimp.2018.05.004. Epub 2018 May 12.
Fisetin, a flavone that can be isolated from fruits and vegetables, has anti-tumor and anti-oxidative properties and ameliorates airway hyperresponsiveness in asthmatic mice. This study investigated whether fisetin can suppress the expression of inflammatory mediators and intercellular adhesion molecule 1 (ICAM-1) in A549 human lung epithelial cells that were stimulated with interleukin-1β (IL-1β) to induce inflammatory responses. A549 cells were treated with fisetin (3-30 μM) and then with IL-1β. Fisetin significantly inhibited COX-2 expression and reduced prostaglandin E production, and it suppressed the levels of IL-8, CCL5, monocyte chemotactic protein 1, tumor necrosis factor α, and IL-6. Fisetin also significantly attenuated the expression of chemokine and inflammatory cytokine genes and decreased the expression of ICAM-1, which mediates THP-1 monocyte adhesion to inflammatory A549 cells. Fisetin decreased the translocation of nuclear transcription factor kappa-B (NF-κB) subunit p65 into the nucleus and inhibited the phosphorylation of proteins in the ERK1/2 pathway. Co-treatment of IL-1β-stimulated A549 cells with ERK1/2 inhibitors plus fisetin reduced ICAM-1 expression. Furthermore, fisetin significantly increased the effects of the protective antioxidant pathway by promoting the expression of nuclear factor erythroid-2-related factor-2 and heme oxygenase 1. Taken together, these data suggest that fisetin has anti-inflammatory effects and that it suppresses the expression of chemokines, inflammatory cytokines, and ICAM-1 by suppressing the NF-κB and ERK1/2 signaling pathways in IL-1β-stimulated human lung epithelial A549 cells.
漆黄素是一种可以从水果和蔬菜中分离出来的类黄酮，具有抗肿瘤和抗氧化特性，并改善哮喘小鼠的气道高反应性。本研究探讨了漆黄素是否可以抑制白细胞介素-1β（IL-1β）刺激人肺上皮 A549 细胞诱导炎症反应时炎症介质和细胞间黏附分子 1（ICAM-1）的表达。用漆黄素（3-30μM）预处理 A549 细胞，然后用 IL-1β 处理。漆黄素显著抑制 COX-2 的表达并减少前列腺素 E 的产生，同时抑制 IL-8、CCL5、单核细胞趋化蛋白 1、肿瘤坏死因子 α 和 IL-6 的水平。漆黄素还显著下调趋化因子和炎症细胞因子基因的表达，并降低介导 THP-1 单核细胞黏附于炎症 A549 细胞的 ICAM-1 的表达。漆黄素减少核转录因子 kappa-B（NF-κB）亚基 p65 向核内的易位，并抑制 ERK1/2 通路中蛋白的磷酸化。IL-1β 刺激的 A549 细胞与 ERK1/2 抑制剂加漆黄素共同处理可降低 ICAM-1 的表达。此外，漆黄素通过促进核因子红细胞 2 相关因子 2 和血红素加氧酶 1 的表达，显著增加了保护性抗氧化途径的作用。综上所述，这些数据表明漆黄素具有抗炎作用，通过抑制 NF-κB 和 ERK1/2 信号通路，抑制 IL-1β 刺激的人肺上皮 A549 细胞中趋化因子、炎症细胞因子和 ICAM-1 的表达。
