The protective effect of eupafolin against TNF-α-induced lung inflammation via the reduction of intercellular cell adhesion molecule-1 expression.

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.

• Authors: Hsin-Ching Sung, Chan-Jung Liang, Chiang-Wen Lee, Feng-Lin Yen, Chien-Yu Hsiao, Shu-Huei Wang, Ya-Fen Jiang-Shieh, Jaw-Shiun Tsai, Yuh-Lien Chen
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 170 Pg. 136-47 (Jul 21 2015) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 25975517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Flavones
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• eupafolin

Topics

• Animals
• Anti-Inflammatory Agents (isolation & purification, pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Flavones (isolation & purification, pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Pneumonia (prevention & control)
• Respiratory Mucosa (cytology, drug effects)
• Tumor Necrosis Factor-alpha (administration & dosage)
• Verbenaceae (chemistry)