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. © 2013 Elsevier Ltd. All rights reserved.

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Author keywords

4-Acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione; Asthma; CCL11; Eosinophil; Ovalbumin

Indexed keywords

EMTREE drug terms: 4 acetyl 3 methyl 6 (3,4,5 trimethoxyphenyl)pyrano[3,4 c]pyran 1,8 dione; dexamethasone; eotaxin; immunoglobulin E; immunoglobulin enhancer binding protein; interleukin 1beta; interleukin 4; myosin light chain 2; ovalbumin; pyran derivative; STAT6 protein; tumor necrosis factor alpha; unclassified drug

EMTREE medical terms: animal experiment; animal model; animal tissue; article; asthma; cell hyperplasia; cell nucleus; controlled study; cytokine release; drug structure; drug synthesis; eosinophil; goblet cell; human; human cell; in vitro study; in vivo study; lung alveolus epithelium; lymphocyte; macrophage; male; mouse; nonhuman; protein expression; protein phosphorylation; protein transport; respiratory tract allergy; smooth muscle fiber

Species Index: Mus; Vitex rotundifolia

Medline keywords: 4-Acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione; 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione; AHR; airway hyperresponsiveness; Asthma; BALF; bronchoalveolar lavage fluid; CCL11; Dexa; dexamethasone; enhanced pause; Eosinophil; H&E; hematoxylin and eosin; HRP; MLC2; myosin light chain 2; OVA; Ovalbumin; ovalbumin; PAS; Penh; periodic acid Schiff; PPY-345; signal transducers and activators of transcription 6; STAT6; streptavidin-horseradish peroxidase; vascular cell adhesion molecule-1; VCAM-1
Medline is the source for the MeSH terms of this document.

MeSH: Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cell Line, Tumor; Cell Survival; Chemokine CCL11; Eosinophils; Humans; Interleukin-1; Interleukin-4; Lymphocytes; Macrophages; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Phosphorylation; Pyrans; Pyrones; STAT6 Transcription Factor; Tumor Necrosis Factor-alpha; Vitex
Medline is the source for the MeSH terms of this document.

Chemicals and CAS Registry Numbers: dexamethasone, 50-02-2; immunoglobulin E, 37341-29-0; ovalbumin, 77466-29-6

Manufacturers:Drug manufacturer: Sigma.