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Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells

SIMPLE SUMMARY: 5-Demethylnobiletin (5-hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone, 5DN) is a bioactive polymethoxyflavone mainly found in citrus plants. To our knowledge, the present study is the first report on the inhibitory mechanism of 5DN and its metabolites on LPS-induced inflammation in RAW...

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Autores principales: Guo, Shanshan, Wu, Xian, Zheng, Jinkai, Song, Mingyue, Dong, Ping, Xiao, Hang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775120/
https://www.ncbi.nlm.nih.gov/pubmed/36552328
http://dx.doi.org/10.3390/biology11121820
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author Guo, Shanshan
Wu, Xian
Zheng, Jinkai
Song, Mingyue
Dong, Ping
Xiao, Hang
author_facet Guo, Shanshan
Wu, Xian
Zheng, Jinkai
Song, Mingyue
Dong, Ping
Xiao, Hang
author_sort Guo, Shanshan
collection PubMed
description SIMPLE SUMMARY: 5-Demethylnobiletin (5-hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone, 5DN) is a bioactive polymethoxyflavone mainly found in citrus plants. To our knowledge, the present study is the first report on the inhibitory mechanism of 5DN and its metabolites on LPS-induced inflammation in RAW 264.7 macrophage cells. Importantly, 5DN’s metabolites showed more potent activities than the parent compound. The possible relationship between the structural properties of 5DN and its metabolites and their anti-inflammatory activity deserves further investigation. ABSTRACT: Hydroxylated polymethoxyflavones (PMFs) are a unique class of flavonoid compounds mainly found in citrus plants. We investigated the anti-inflammatory effects of one major 5-hydroxy PMF, namely 5-demethylnobiletin (5DN) and its metabolites 5, 3′-didemethylnobiletin (M1), 5, 4′-didemethylnobiletin (M2), and 5, 3′, 4′-tridemethylnobiletin (M3) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that M2 and M3 produced stronger inhibitory effects on the production of nitric oxide (NO) than their parent compound at non-cytotoxic concentrations. Western blotting and real-time PCR analyses demonstrated that M2 and M3 significantly decreased iNOS and COX-2 gene expression. The results also showed that M1 and M3 induced heme oxygenase-1(HO-1) gene expression. Overall, our results demonstrated that metabolites of 5DN significantly inhibited LPS-induced inflammation in RAW 264.7 macrophage cells and generally possessed more potent anti-inflammatory activity than the parent compound, 5DN.
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spelling pubmed-97751202022-12-23 Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells Guo, Shanshan Wu, Xian Zheng, Jinkai Song, Mingyue Dong, Ping Xiao, Hang Biology (Basel) Article SIMPLE SUMMARY: 5-Demethylnobiletin (5-hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone, 5DN) is a bioactive polymethoxyflavone mainly found in citrus plants. To our knowledge, the present study is the first report on the inhibitory mechanism of 5DN and its metabolites on LPS-induced inflammation in RAW 264.7 macrophage cells. Importantly, 5DN’s metabolites showed more potent activities than the parent compound. The possible relationship between the structural properties of 5DN and its metabolites and their anti-inflammatory activity deserves further investigation. ABSTRACT: Hydroxylated polymethoxyflavones (PMFs) are a unique class of flavonoid compounds mainly found in citrus plants. We investigated the anti-inflammatory effects of one major 5-hydroxy PMF, namely 5-demethylnobiletin (5DN) and its metabolites 5, 3′-didemethylnobiletin (M1), 5, 4′-didemethylnobiletin (M2), and 5, 3′, 4′-tridemethylnobiletin (M3) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that M2 and M3 produced stronger inhibitory effects on the production of nitric oxide (NO) than their parent compound at non-cytotoxic concentrations. Western blotting and real-time PCR analyses demonstrated that M2 and M3 significantly decreased iNOS and COX-2 gene expression. The results also showed that M1 and M3 induced heme oxygenase-1(HO-1) gene expression. Overall, our results demonstrated that metabolites of 5DN significantly inhibited LPS-induced inflammation in RAW 264.7 macrophage cells and generally possessed more potent anti-inflammatory activity than the parent compound, 5DN. MDPI 2022-12-14 /pmc/articles/PMC9775120/ /pubmed/36552328 http://dx.doi.org/10.3390/biology11121820 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guo, Shanshan
Wu, Xian
Zheng, Jinkai
Song, Mingyue
Dong, Ping
Xiao, Hang
Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells
title Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells
title_full Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells
title_fullStr Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells
title_full_unstemmed Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells
title_short Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells
title_sort anti-inflammatory property of 5-demethylnobiletin (5-hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone) and its metabolites in lipopolysaccharide (lps)-induced raw 264.7 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775120/
https://www.ncbi.nlm.nih.gov/pubmed/36552328
http://dx.doi.org/10.3390/biology11121820
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