Abstract
Flavonoids have beneficial activities which modulate oxidative stress, allergy, tumor growth and viral infection, and which stimulate apoptosis of tumor cells. In addition to these activities, dietary flavonoids are able to regulate acute and chronic inflammatory responses. Here we describe new aspects of regulatory mechanisms by which flavonoids suppress production of tumor necrosis factor-α (TNF-α) by macrophages, microglial cells and mast cells stimulated with lipopolysaccharide (LPS) and others via toll-like receptors (TLRs), and TNF-α-mediated acute and chronic inflammatory responses. Treatment with flavonoids such as luteolin, apigenin, quercetin, genistein, (-)-epigallocatechin gallate, and anthocyanidin resulted in significant downregulation of LPS-elicited TNF-α and nitric oxide (NO) production and diminished lethal shock. In chronic diseases, pathogenesis of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis which is triggered by TNF-α, was improved by the oral administration of flavonoids after the onset of CIA. Here, we discuss that inhibitory effects of flavonoids on acute and chronic inflammation are due to regulation of signaling pathways, including the nuclear factor κB (NF-κB) activation and mitogen-activated protein (MAP) kinase family phosphorylation. FcεRI expression by NF-κB activation was also reduced by flavonoids; while accumulation of lipid rafts, which is the critical step for signaling, was blocked by flavonoids. The intake of dietary flavonoids reduces acute and chronic inflammation due to blocking receptor accumulation and signaling cascades, and would assist individuals at highrisk from life-style related diseases.
Keywords: isoflavones, Proinflammatory cytokines, inflammatory diseases, TNF receptor 1, lipopolysaccharide (LPS)
Current Pharmaceutical Design
Title: Immunomodulating Effects of Flavonoids on Acute and Chronic Inflammatory Responses Caused by Tumor Necrosis Factor α
Volume: 12 Issue: 32
Author(s): Yoshio Kumazawa, Kiichiro Kawaguchi and Hiroaki Takimoto
Affiliation:
Keywords: isoflavones, Proinflammatory cytokines, inflammatory diseases, TNF receptor 1, lipopolysaccharide (LPS)
Abstract: Flavonoids have beneficial activities which modulate oxidative stress, allergy, tumor growth and viral infection, and which stimulate apoptosis of tumor cells. In addition to these activities, dietary flavonoids are able to regulate acute and chronic inflammatory responses. Here we describe new aspects of regulatory mechanisms by which flavonoids suppress production of tumor necrosis factor-α (TNF-α) by macrophages, microglial cells and mast cells stimulated with lipopolysaccharide (LPS) and others via toll-like receptors (TLRs), and TNF-α-mediated acute and chronic inflammatory responses. Treatment with flavonoids such as luteolin, apigenin, quercetin, genistein, (-)-epigallocatechin gallate, and anthocyanidin resulted in significant downregulation of LPS-elicited TNF-α and nitric oxide (NO) production and diminished lethal shock. In chronic diseases, pathogenesis of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis which is triggered by TNF-α, was improved by the oral administration of flavonoids after the onset of CIA. Here, we discuss that inhibitory effects of flavonoids on acute and chronic inflammation are due to regulation of signaling pathways, including the nuclear factor κB (NF-κB) activation and mitogen-activated protein (MAP) kinase family phosphorylation. FcεRI expression by NF-κB activation was also reduced by flavonoids; while accumulation of lipid rafts, which is the critical step for signaling, was blocked by flavonoids. The intake of dietary flavonoids reduces acute and chronic inflammation due to blocking receptor accumulation and signaling cascades, and would assist individuals at highrisk from life-style related diseases.
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Cite this article as:
Kumazawa Yoshio, Kawaguchi Kiichiro and Takimoto Hiroaki, Immunomodulating Effects of Flavonoids on Acute and Chronic Inflammatory Responses Caused by Tumor Necrosis Factor α, Current Pharmaceutical Design 2006; 12 (32) . https://dx.doi.org/10.2174/138161206778743565
DOI https://dx.doi.org/10.2174/138161206778743565 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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