1. A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma.
- Author
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Chung HS, Kim Y, Oh SJ, Kim H, Choi SI, Zhang Y, Jeong JH, and Bae H
- Subjects
- Animals, Anti-Asthmatic Agents pharmacology, Anti-Asthmatic Agents therapeutic use, Asthma drug therapy, Asthma pathology, Bronchoalveolar Lavage Fluid cytology, Cell Line, Tumor, Cell Survival drug effects, Chemokine CCL11 metabolism, Eosinophils cytology, Eosinophils drug effects, Humans, Interleukin-1 pharmacology, Interleukin-4 pharmacology, Lymphocytes cytology, Lymphocytes drug effects, Macrophages cytology, Macrophages drug effects, Male, Mice, Mice, Inbred BALB C, NF-kappa B metabolism, Ovalbumin toxicity, Phosphorylation drug effects, Pyrans chemistry, Pyrans therapeutic use, Pyrans toxicity, Pyrones pharmacology, Pyrones therapeutic use, STAT6 Transcription Factor metabolism, Tumor Necrosis Factor-alpha pharmacology, Vitex chemistry, Vitex metabolism, Anti-Asthmatic Agents chemical synthesis, Asthma chemically induced, Pyrones chemical synthesis
- Abstract
Eosinophilia is one of the characteristic signs of allergic inflammation. Massive migration of eosinophils to the airways can cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. Previously, we discovered a new compound, 1H,8H-pyrano[3,4-c]pyran-1,8-dione (PPY), derived from the fruit of Vitex rotundifolia L. and evaluated its anti-inflammatory and anti-asthmatic properties. In this study, we synthesized a new modified compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl) pyrano[3,4-c]pyran-1,8-dione (PPY-345), which was based on the PPY skeleton, and we evaluated its anti-asthmatic effects. To evaluate the anti-asthmatic effect of PPY-345 in vitro, A549 lung epithelial cells were stimulated with TNF-alpha, IL-4 and IL-1-beta to induce the expression of CCL11 (Eotaxin), a chemokine involved in eosinophil chemotaxis. To characterize the anti-asthmatic properties of PPY-345 in vivo, we examined the influence of PPY-345 in an ovalbumin (OVA)-induced asthma model. PPY-345 treatments significantly reduced CCL11 secretion. PPY-345 treatment did not inhibit the translocation of NF-κB into the nucleus but suppressed the phosphorylation of signal transducers and activators of transcription 6 (STAT6). PPY-345 treatment significantly reduced airway hyperreactivity as measured by whole-body plethysmography. PPY-345 further reduced total cells, including eosinophil, macrophage and lymphocytes, in the BAL fluid, goblet cell hyperplasia and myosin light chain 2 positive smooth muscle cell area in the lung tissue. Additionally, PPY-345 significantly suppressed the levels of OVA-IgE present in the serum. These results suggested that PPY-345 could improve asthma symptoms in OVA-sensitized mice., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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