Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced

Inflammation is a response of immune system towards cell injury caused by trauma or infection. In laboratory, inflammation can be studied by using macrophage cell models activated with lipopolysaccharide (LPS). Momordica charantia (M. charantia) or bitter gourds is known for its anti-diabetic activi...

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Main Author:	Lee, Shi Yan
Format:	Thesis
Language:	English
Published:	2021
Subjects:	TP Chemical technology
Online Access:	http://eprints.utm.my/id/eprint/101760/1/LeeShiyanPSChE2021.pdf
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spelling	my-utm-ep.1017602023-07-10T09:25:38Z Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced 2021 Lee, Shi Yan TP Chemical technology Inflammation is a response of immune system towards cell injury caused by trauma or infection. In laboratory, inflammation can be studied by using macrophage cell models activated with lipopolysaccharide (LPS). Momordica charantia (M. charantia) or bitter gourds is known for its anti-diabetic activity and but its antiinflammatory activity is not established. In addition, the connection between inflammation with perturbed glucose metabolism has not been fully elucidated. The aim of this project is to implement a combined cell-based assay, gene expression analysis, and metabolomics approach to investigate the anti-inflammatory and antiglycolytic activities of M. charantia, and to characterise the metabolic changes associated with its anti-inflammatory action using a murine macrophage cell model. The results showed that M. charantia treatment inhibited the LPS-induced NF-?B nuclear translocation and downregulated pro-inflammatory IL6 (-84.7 %), TNF-a (- 85.1 %), IL1ß (-94.2 %), COX2 (-89.5 %), and iNOS (-28.8 %) genes. In addition, M. charantia treatment suppressed LPS-induced GLUT1 expression (-94.3 %) and lactate production (-28 %), supporting a potential role of glucose metabolism in inflammation. The findings suggested that the anti-inflammatory effect of M. charantia may be associated with the regulation of glycolysis and the tricarboxylic acid (TCA) cycle, modulation of amino acid metabolism, and the action of potential anti-inflammatory metabolites in M. charantia. In addition, the present study also provided new findings showing anti-inflammatory and anti-glycolytic effect of charantin. Charantin is a key bioactive compound in M. charantia known for its hypoglycemic property but the antiinflammatory potential of charantin has yet to be elucidated. It is a 1:1 mixture of two compounds including sitosterol glucoside and stigmasterol glucoside. In this study, charantin and each of its components were found to exert anti-inflammatory activities by suppressing the IL6, TNF-a, iNOS, TLR4, MCP1, GLUT1 and HK2 genes expression. Both components also showed synergistic inhibitory effect on IL1ß nd COX2 genes expression. Furthermore, charantin and stigmasterol glucoside were found to partially inhibited NF-?B translocation, significantly inhibited p-38 MAPK phosphorylation, and reduced lactate production in the LPS-induced RAW264.7 cells. In this study, the anti-inflammatory and anti-glycolytic activities of aqueous M. charantia extract and charantin were found to share consistent results. To further investigate the link between the anti-inflammatory effect and perturbed glucose metabolism, an experiment was performed to study the potential anti-inflammatory strategy by targeting GLUT1 using WZB117, a specific GLUT1 inhibitor. WZB117 downregulated the expressions of IL6 (-93.3 %), TNF-a (-63.2 %), IL1ß (-76.1 %), COX2 (-41.34 %), iNOS (-98.48 %), MCP1 (-85.59 %), and GLUT1 (-85.51 %) in the LPS-induced RAW264.7 cells. In addition, WZB117 also reduced LPS-induced lactate production by 11.16 %. Taken together, The present study highlighted antiinflammatory and anti-glycolytic effects of M. charantia and charantin, and provided evidence showing perturbed glucose metabolism in inflammatory response. The current results supported a therapeutic strategy against inflammation by targeting glucose metabolism. 2021 Thesis http://eprints.utm.my/id/eprint/101760/ http://eprints.utm.my/id/eprint/101760/1/LeeShiyanPSChE2021.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:145695 phd doctoral Universiti Teknologi Malaysia Faculty of Engineering - School of Chemical & Energy Engineering
institution	Universiti Teknologi Malaysia
collection	UTM Institutional Repository
language	English
topic	TP Chemical technology
spellingShingle	TP Chemical technology Lee, Shi Yan Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
description	Inflammation is a response of immune system towards cell injury caused by trauma or infection. In laboratory, inflammation can be studied by using macrophage cell models activated with lipopolysaccharide (LPS). Momordica charantia (M. charantia) or bitter gourds is known for its anti-diabetic activity and but its antiinflammatory activity is not established. In addition, the connection between inflammation with perturbed glucose metabolism has not been fully elucidated. The aim of this project is to implement a combined cell-based assay, gene expression analysis, and metabolomics approach to investigate the anti-inflammatory and antiglycolytic activities of M. charantia, and to characterise the metabolic changes associated with its anti-inflammatory action using a murine macrophage cell model. The results showed that M. charantia treatment inhibited the LPS-induced NF-?B nuclear translocation and downregulated pro-inflammatory IL6 (-84.7 %), TNF-a (- 85.1 %), IL1ß (-94.2 %), COX2 (-89.5 %), and iNOS (-28.8 %) genes. In addition, M. charantia treatment suppressed LPS-induced GLUT1 expression (-94.3 %) and lactate production (-28 %), supporting a potential role of glucose metabolism in inflammation. The findings suggested that the anti-inflammatory effect of M. charantia may be associated with the regulation of glycolysis and the tricarboxylic acid (TCA) cycle, modulation of amino acid metabolism, and the action of potential anti-inflammatory metabolites in M. charantia. In addition, the present study also provided new findings showing anti-inflammatory and anti-glycolytic effect of charantin. Charantin is a key bioactive compound in M. charantia known for its hypoglycemic property but the antiinflammatory potential of charantin has yet to be elucidated. It is a 1:1 mixture of two compounds including sitosterol glucoside and stigmasterol glucoside. In this study, charantin and each of its components were found to exert anti-inflammatory activities by suppressing the IL6, TNF-a, iNOS, TLR4, MCP1, GLUT1 and HK2 genes expression. Both components also showed synergistic inhibitory effect on IL1ß nd COX2 genes expression. Furthermore, charantin and stigmasterol glucoside were found to partially inhibited NF-?B translocation, significantly inhibited p-38 MAPK phosphorylation, and reduced lactate production in the LPS-induced RAW264.7 cells. In this study, the anti-inflammatory and anti-glycolytic activities of aqueous M. charantia extract and charantin were found to share consistent results. To further investigate the link between the anti-inflammatory effect and perturbed glucose metabolism, an experiment was performed to study the potential anti-inflammatory strategy by targeting GLUT1 using WZB117, a specific GLUT1 inhibitor. WZB117 downregulated the expressions of IL6 (-93.3 %), TNF-a (-63.2 %), IL1ß (-76.1 %), COX2 (-41.34 %), iNOS (-98.48 %), MCP1 (-85.59 %), and GLUT1 (-85.51 %) in the LPS-induced RAW264.7 cells. In addition, WZB117 also reduced LPS-induced lactate production by 11.16 %. Taken together, The present study highlighted antiinflammatory and anti-glycolytic effects of M. charantia and charantin, and provided evidence showing perturbed glucose metabolism in inflammatory response. The current results supported a therapeutic strategy against inflammation by targeting glucose metabolism.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Lee, Shi Yan
author_facet	Lee, Shi Yan
author_sort	Lee, Shi Yan
title	Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
title_short	Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
title_full	Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
title_fullStr	Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
title_full_unstemmed	Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
title_sort	anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced
granting_institution	Universiti Teknologi Malaysia
granting_department	Faculty of Engineering - School of Chemical & Energy Engineering
publishDate	2021
url	http://eprints.utm.my/id/eprint/101760/1/LeeShiyanPSChE2021.pdf
_version_	1776100765029367808

Anti-inflammatory and anti-glycolytic effect of momordica charantia aqueous extract and charantin in lipopolysaccharide induced

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