Hsin-Ching Sung1, Chan-Jung Liang2, Chiang-Wen Lee3, Feng-Lin Yen4, Chien-Yu Hsiao5, Shu-Huei Wang6, Ya-Fen Jiang-Shieh7, Jaw-Shiun Tsai8, Yuh-Lien Chen9. 1. Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 2. Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan; Center for Lipid and Glycomedicine Research (CLGR), Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Lipid Biosciences (CLB), Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 3. Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. 4. Department of France and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan. 6. Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan. 7. Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 8. Department of Family Medicine and Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: jawshiun@ntu.edu.tw. 9. Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan. Electronic address: ylchenv@ntu.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Eupafolin, a major bioactive compound found in Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell adhesion molecules in the lung airway epithelium is associated with the epithelium-leukocyte interaction and plays a critical role in the pathogenesis of lung airway inflammatory disorders. To investigate the effects of eupafolin on tumor necrosis factor-α (TNF-α)-induced intercellular cell adhesion molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the underlying mechanisms. MATERIALS AND METHODS: The effect of eupafolin on ICAM-1 expression in A549 cells were examined by Western blotting and immunofluorescent staining. The mice were injected intraperitoneally with or without eupafolin and then were left untreated or were injected intratracheally with TNF-α. To detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also examined by Western blotting and immunohistochemical staining. RESULTS: Eupafolin pretreatment reduced the TNF-α-induced ICAM-1 expression and also the ERK1/2, JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1 expression with TNF-α treatment was unaffected by p38 and PI3K inhibitors. Eupafolin decreased the TNF-α-induced NF-κB p65 activation and its nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the lung tissues of TNF-α-treated mice. CONCLUSIONS: Eupafolin exerts its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear translocation of NF-κB p65. These results suggest that eupafolin may represent a novel therapeutic agent targeting epithelial activation in lung inflammation.
ETHNOPHARMACOLOGICAL RELEVANCE: Eupafolin, a major bioactive compound found in Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell adhesion molecules in the lung airway epithelium is associated with the epithelium-leukocyte interaction and plays a critical role in the pathogenesis of lung airway inflammatory disorders. To investigate the effects of eupafolin on tumornecrosis factor-α (TNF-α)-induced intercellular cell adhesion molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the underlying mechanisms. MATERIALS AND METHODS: The effect of eupafolin on ICAM-1 expression in A549 cells were examined by Western blotting and immunofluorescent staining. The mice were injected intraperitoneally with or without eupafolin and then were left untreated or were injected intratracheally with TNF-α. To detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also examined by Western blotting and immunohistochemical staining. RESULTS:Eupafolin pretreatment reduced the TNF-α-induced ICAM-1 expression and also the ERK1/2, JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1 expression with TNF-α treatment was unaffected by p38 and PI3K inhibitors. Eupafolin decreased the TNF-α-induced NF-κB p65 activation and its nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the lung tissues of TNF-α-treated mice. CONCLUSIONS:Eupafolin exerts its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear translocation of NF-κB p65. These results suggest that eupafolin may represent a novel therapeutic agent targeting epithelial activation in lung inflammation.