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.