A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma.
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.
Department of Physiology, College of Korean Medicine, Kyung Hee University, #1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
Hwan-Suck
HS
Chung
Youngeun
Y
Kim
Sei Joong
SJ
Oh
Hankyum
H
Kim
Seung Ill
SI
Choi
Yujuan
Y
Zhang
Jin-Hyun
JH
Jeong
Hyunsu
H
Bae
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054413:Chemokine CCL11 / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D011714:Pyrans / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D050800:STAT6 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020950:Vitex / Q000737:chemistry / Q000378:metabolism
C588112:4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl) pyrano(3,4-c)pyran-1,8-dione; D018927:Anti-Asthmatic Agents; D054413:Chemokine CCL11; D007375:Interleukin-1; D016328:NF-kappa B; D011714:Pyrans; D011753:Pyrones; D050800:STAT6 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D010047:Ovalbumin
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; Asthma; BALF; CCL11; Dexa; Eosinophil; H&E; HRP; MLC2; OVA; Ovalbumin; PAS; PPY-345; Penh; STAT6; VCAM-1; airway hyperresponsiveness; bronchoalveolar lavage fluid; dexamethasone; enhanced pause; hematoxylin and eosin; myosin light chain 2; ovalbumin; periodic acid Schiff; signal transducers and activators of transcription 6; streptavidin-horseradish peroxidase; vascular cell adhesion molecule-1