Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma

Diverse heterocyclic compound’s production involved chalcones. Many studies have proven that chalcone derivative compound possess assorted biological activities such as antimicrobial, anti-inflammatory, analgesic, antiplatelet, antiulcerative, antimalarial, anticancer and antiviral properties. Carda...

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Main Author:	Rajajendram, Revathee
Format:	Thesis
Language:	English
Published:	2014
Subjects:	Asthma Anti-Asthmatic Agents - chemistry
Online Access:	http://psasir.upm.edu.my/id/eprint/55643/1/FPSK%28m%29%202014%2052RR.pdf
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id	my-upm-ir.55643
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spelling	my-upm-ir.556432017-06-06T05:07:27Z Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma 2014-02 Rajajendram, Revathee Diverse heterocyclic compound’s production involved chalcones. Many studies have proven that chalcone derivative compound possess assorted biological activities such as antimicrobial, anti-inflammatory, analgesic, antiplatelet, antiulcerative, antimalarial, anticancer and antiviral properties. Cardamonin’s analogues 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (L31) was synthesized. Cell viability was resolved by conducting MTT cytotoxicity assay. L31 has a firm suppression effect upon eotaxin, MCP-1 and RANTES but did not inhibit the secretion of chemokines GRO-α and IL-8. The molecular target of L31 on several major proinflammatory pathways was furtherdissected. The results from western blots reveal that L31 targets the NF-kB but not the MAPK pathway. These findings confirm the selectivity and specificityof L31. Dose-response studies were conducted on female Balb/c mice in which doses (0.2, 2, 20 and 100 mg/kg) of L31 were administered intraperitoneally to mice following sensitization and aerosolized doses of ovalbumin (OVA). Mice were then subjected to methacholine challenge with an ultrasonic nebulizer and airway hyperresponsiveness was determined by comparison of enhanced pause (Penh) responses. Whole-body plethysmography system (Buxco) was used to measure the Penh value. Analysis of bronchoalveolar lavage (BALF) showed that all doses of L31 caused significant reduction in airway eosinophilia, tissue inflammatory scores and goblet cell metaplasia. L31 suppressed the secretion of eotaxin, RANTES, interleukin (IL) 4, IL 5 and IL 13.L31 also inhibits the gene expression of the all the mediator except for IL13. Collectively,these findings are vital in making decisions for further development of L31 compounds into anti-inflammatory and anti-asthmatic drug. The ultimate aim would be to enter clinical trials since the current therapy involves administration of combinations of steroids and β-agonists which in long term would mask untreated inflammation and lead to a higher risk of adverse outcomes. Asthma Anti-Asthmatic Agents - chemistry 2014-02 Thesis http://psasir.upm.edu.my/id/eprint/55643/ http://psasir.upm.edu.my/id/eprint/55643/1/FPSK%28m%29%202014%2052RR.pdf application/pdf en public masters Universiti Putra Malaysia Asthma Anti-Asthmatic Agents - chemistry
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Asthma Anti-Asthmatic Agents - chemistry
spellingShingle	Asthma Anti-Asthmatic Agents - chemistry Rajajendram, Revathee Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma
description	Diverse heterocyclic compound’s production involved chalcones. Many studies have proven that chalcone derivative compound possess assorted biological activities such as antimicrobial, anti-inflammatory, analgesic, antiplatelet, antiulcerative, antimalarial, anticancer and antiviral properties. Cardamonin’s analogues 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (L31) was synthesized. Cell viability was resolved by conducting MTT cytotoxicity assay. L31 has a firm suppression effect upon eotaxin, MCP-1 and RANTES but did not inhibit the secretion of chemokines GRO-α and IL-8. The molecular target of L31 on several major proinflammatory pathways was furtherdissected. The results from western blots reveal that L31 targets the NF-kB but not the MAPK pathway. These findings confirm the selectivity and specificityof L31. Dose-response studies were conducted on female Balb/c mice in which doses (0.2, 2, 20 and 100 mg/kg) of L31 were administered intraperitoneally to mice following sensitization and aerosolized doses of ovalbumin (OVA). Mice were then subjected to methacholine challenge with an ultrasonic nebulizer and airway hyperresponsiveness was determined by comparison of enhanced pause (Penh) responses. Whole-body plethysmography system (Buxco) was used to measure the Penh value. Analysis of bronchoalveolar lavage (BALF) showed that all doses of L31 caused significant reduction in airway eosinophilia, tissue inflammatory scores and goblet cell metaplasia. L31 suppressed the secretion of eotaxin, RANTES, interleukin (IL) 4, IL 5 and IL 13.L31 also inhibits the gene expression of the all the mediator except for IL13. Collectively,these findings are vital in making decisions for further development of L31 compounds into anti-inflammatory and anti-asthmatic drug. The ultimate aim would be to enter clinical trials since the current therapy involves administration of combinations of steroids and β-agonists which in long term would mask untreated inflammation and lead to a higher risk of adverse outcomes.
format	Thesis
qualification_level	Master's degree
author	Rajajendram, Revathee
author_facet	Rajajendram, Revathee
author_sort	Rajajendram, Revathee
title	Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma
title_short	Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma
title_full	Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma
title_fullStr	Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma
title_full_unstemmed	Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma
title_sort	anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (l31) in lung epithelial cells and on airway inflammation in a murine model of asthma
granting_institution	Universiti Putra Malaysia
publishDate	2014
url	http://psasir.upm.edu.my/id/eprint/55643/1/FPSK%28m%29%202014%2052RR.pdf
_version_	1747812106409869312

Anti-inflammatory properties of 3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (L31) in lung epithelial cells and on airway inflammation in a murine model of asthma

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