Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways
碩士 === 嘉南藥理科技大學 === 生物科技系暨研究所 === 92 === Inflammatory response is typically represented by a cascade of vascular and cellular reactions caused by injury and infection. The activation of macrophages is a key event for the initiation and propagation of these defensive reactions. When stimulated with p...
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ndltd-TW-092CNUP51110022015-10-13T13:04:21Z http://ndltd.ncl.edu.tw/handle/06791194863420101228 Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways 香茹之抗發炎幼躉P抑制NF-kB及MAPK訊息傳導路徑有關 Ching-Yi Weng 翁菁憶 碩士 嘉南藥理科技大學 生物科技系暨研究所 92 Inflammatory response is typically represented by a cascade of vascular and cellular reactions caused by injury and infection. The activation of macrophages is a key event for the initiation and propagation of these defensive reactions. When stimulated with pathologic stimuli or injury, macrophages release nitric oxide, PGE2, TNF-a, IL-1b, IL-6 and IL-12. In addition, T cells secret IFN-g and other pro-inflammatory cytokines that augment defense against invasion. The sustained inflammatory mediator production has been implicated associated with the pathologic process of inflammatory disease. Thus, the inhibition of over production of inflammatory mediators stands as an important therapeutic goal for drug development. Glossogyne tenuifolia (Hsiang-Ju) is an anti-pyretic herb in Chinese medicine. In previons investigation, the ethanol extract from Glossogyne tenuifolia (GT) inhibits pro-inflammatory mediators release in murine macrophage-like cell line, RAW 264.7 cells. In this study, in order to further investigate the anti-inflammatory effects and mechanisms of ethanol extract of G. tenuifolia Cassini (GT) on LPS-stimulated BALB/c mouse peritoneal macrophages and spleen cells as well as human whole blood and peripheral blood mononuclear cells (PBMC). In the present study demonstrated the production of pro-inflammatory mediators, NO, PGE2, IL-1b, IL-6 and IL-12 as well as IFN-g, were attenuated by the ethanol extract of G. tenuifolia (GT) in LPS-activated mouse peritoneal macrophages and PHA-stimulated mouse splenocytes, respectively. GT also attenuates inflammatory cytokines synthesis in human whole blood and PBMC. To determine the mechanism by which GT inhibits LPS signaling, this study results showed GT downregulates iNOS and COX-2 promoter activity, thus inhibiting NO and PGE2 release in LPS-activated mouse peritoneal macrophages. In addition, GT exerted inhibition of the LPS-stimulated expression of the proinflammatory cytokines through post-transcriptional mechanisms. Moreover, we focused on nuclear factor-kB (NF-kB) activation and mitogen-activated protein kinases (MAPKs). The electrophoretic mobility shift assay (EMSA) demonstrated that GT attenuated LPS-mediated kB DNA binding activity in RAW264.7 cells, peritoneal macrophages, and spleen cells. Moreover, Western blot analysis revealed that GT inhibited the phosphorylation of p38 MAPK, JNK and ERK in activated RAW 264.7 cells; and the phosphorylation of p38, JNK and ERK in activated peritoneal macrophages. Our result demonstrated that GT interferes NF-kB- and MAPK-mediated gene expression therefore inhibits inflammatory mediators release. Choi-Lan Ha Ming-Jiuan Wu 夏彩蘭 吳明娟 2004 學位論文 ; thesis 118 zh-TW |
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碩士 === 嘉南藥理科技大學 === 生物科技系暨研究所 === 92 === Inflammatory response is typically represented by a cascade of vascular and cellular reactions caused by injury and infection. The activation of macrophages is a key event for the initiation and propagation of these defensive reactions. When stimulated with pathologic stimuli or injury, macrophages release nitric oxide, PGE2, TNF-a, IL-1b, IL-6 and IL-12. In addition, T cells secret IFN-g and other pro-inflammatory cytokines that augment defense against invasion. The sustained inflammatory mediator production has been implicated associated with the pathologic process of inflammatory disease. Thus, the inhibition of over production of inflammatory mediators stands as an important therapeutic goal for drug development.
Glossogyne tenuifolia (Hsiang-Ju) is an anti-pyretic herb in Chinese medicine.
In previons investigation, the ethanol extract from Glossogyne tenuifolia (GT) inhibits pro-inflammatory mediators release in murine macrophage-like cell line, RAW 264.7 cells. In this study, in order to further investigate the anti-inflammatory effects and mechanisms of ethanol extract of G. tenuifolia Cassini (GT) on LPS-stimulated BALB/c mouse peritoneal macrophages and spleen cells as well as human whole blood and peripheral blood mononuclear cells (PBMC).
In the present study demonstrated the production of pro-inflammatory mediators, NO, PGE2, IL-1b, IL-6 and IL-12 as well as IFN-g, were attenuated by the ethanol extract of G. tenuifolia (GT) in LPS-activated mouse peritoneal macrophages and PHA-stimulated mouse splenocytes, respectively. GT also attenuates inflammatory cytokines synthesis in human whole blood and PBMC. To determine the mechanism by which GT inhibits LPS signaling, this study results showed GT downregulates iNOS and COX-2 promoter activity, thus inhibiting NO and PGE2 release in LPS-activated mouse peritoneal macrophages. In addition, GT exerted inhibition of the LPS-stimulated expression of the proinflammatory cytokines through post-transcriptional mechanisms. Moreover, we focused on nuclear factor-kB (NF-kB) activation and mitogen-activated protein kinases (MAPKs). The electrophoretic mobility shift assay (EMSA) demonstrated that GT attenuated LPS-mediated kB DNA binding activity in RAW264.7 cells, peritoneal macrophages, and spleen cells. Moreover, Western blot analysis revealed that GT inhibited the phosphorylation of p38 MAPK, JNK and ERK in activated RAW 264.7 cells; and the phosphorylation of p38, JNK and ERK in activated peritoneal macrophages. Our result demonstrated that GT interferes NF-kB- and MAPK-mediated gene expression therefore inhibits inflammatory mediators release.
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author2 |
Choi-Lan Ha |
author_facet |
Choi-Lan Ha Ching-Yi Weng 翁菁憶 |
author |
Ching-Yi Weng 翁菁憶 |
spellingShingle |
Ching-Yi Weng 翁菁憶 Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways |
author_sort |
Ching-Yi Weng |
title |
Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways |
title_short |
Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways |
title_full |
Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways |
title_fullStr |
Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways |
title_full_unstemmed |
Anti-Inflammatory Effect of Glossogyne tenuifolia Is Mediated through Down-Regulating NF-kB and MAPK Signaling Pathways |
title_sort |
anti-inflammatory effect of glossogyne tenuifolia is mediated through down-regulating nf-kb and mapk signaling pathways |
publishDate |
2004 |
url |
http://ndltd.ncl.edu.tw/handle/06791194863420101228 |
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