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A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma.
Bioorg Med Chem 2013; 21(21):6359-65BM

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.

Authors+Show Affiliations

Department of Physiology, College of Korean Medicine, Kyung Hee University, #1 Hoeki-Dong, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24054491

Citation

Chung, Hwan-Suck, et al. "A Synthetic Compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, Ameliorates Ovalbumin-induced Asthma." Bioorganic & Medicinal Chemistry, vol. 21, no. 21, 2013, pp. 6359-65.
Chung HS, Kim Y, Oh SJ, et al. A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma. Bioorg Med Chem. 2013;21(21):6359-65.
Chung, H. S., Kim, Y., Oh, S. J., Kim, H., Choi, S. I., Zhang, Y., ... Bae, H. (2013). A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma. Bioorganic & Medicinal Chemistry, 21(21), pp. 6359-65. doi:10.1016/j.bmc.2013.08.045.
Chung HS, et al. A Synthetic Compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, Ameliorates Ovalbumin-induced Asthma. Bioorg Med Chem. 2013 Nov 1;21(21):6359-65. PubMed PMID: 24054491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma. AU - Chung,Hwan-Suck, AU - Kim,Youngeun, AU - Oh,Sei Joong, AU - Kim,Hankyum, AU - Choi,Seung Ill, AU - Zhang,Yujuan, AU - Jeong,Jin-Hyun, AU - Bae,Hyunsu, Y1 - 2013/09/03/ PY - 2013/07/02/received PY - 2013/08/19/revised PY - 2013/08/24/accepted PY - 2013/9/24/entrez PY - 2013/9/24/pubmed PY - 2014/5/27/medline KW - 4-Acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione KW - 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione KW - AHR KW - Asthma KW - BALF KW - CCL11 KW - Dexa KW - Eosinophil KW - H&E KW - HRP KW - MLC2 KW - OVA KW - Ovalbumin KW - PAS KW - PPY-345 KW - Penh KW - STAT6 KW - VCAM-1 KW - airway hyperresponsiveness KW - bronchoalveolar lavage fluid KW - dexamethasone KW - enhanced pause KW - hematoxylin and eosin KW - myosin light chain 2 KW - ovalbumin KW - periodic acid Schiff KW - signal transducers and activators of transcription 6 KW - streptavidin-horseradish peroxidase KW - vascular cell adhesion molecule-1 SP - 6359 EP - 65 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 21 IS - 21 N2 - 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. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/24054491/A_synthetic_compound_4_acetyl_3_methyl_6__345_trimethoxyphenyl_pyrano[34_c]pyran_18_dione_ameliorates_ovalbumin_induced_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(13)00748-7 DB - PRIME DP - Unbound Medicine ER -