Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway

Biorenovation, a microbial enzyme-assisted degradation process of precursor compounds, is an effective approach to unraveling the potential bioactive properties of the derived compounds. In this study, we obtained a new compound, prunetin 4′-<i>O</i>-phosphate (P4P), through the biorenov...

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Autores principales:	Tae-Jin Park, Hyehyun Hong, Min-Seon Kim, Jin-Soo Park, Won-Jae Chi, Seung-Young Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prunetin 4′-<i>O</i>-phosphate prunetin anti-inflammatory activities biorenovation phosphorylation MAPK signaling Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/3b40f85073d742a59dd5a83f00c4ab12
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spelling	oai:doaj.org-article:3b40f85073d742a59dd5a83f00c4ab122021-11-25T18:27:40ZPrunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway10.3390/molecules262268411420-3049https://doaj.org/article/3b40f85073d742a59dd5a83f00c4ab122021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6841https://doaj.org/toc/1420-3049Biorenovation, a microbial enzyme-assisted degradation process of precursor compounds, is an effective approach to unraveling the potential bioactive properties of the derived compounds. In this study, we obtained a new compound, prunetin 4′-<i>O</i>-phosphate (P4P), through the biorenovation of prunetin (PRN), and investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. The anti-inflammatory effect of P4P was evaluated by measuring the production of prostaglandin-E<sub>2</sub> (PGE<sub>2</sub>), nitric oxide (NO), which is an inflammation-inducing factor, and related cytokines such as tumor necrosis factor-α (TNFα), interleukin-1β (IL1β), and interleukin-6 (IL6). The findings demonstrated that P4P was non-toxic to cells, and its inhibition of the secretion of NO—as well as pro-inflammatory cytokines—was concentration-dependent. A simultaneous reduction in the protein expression level of pro-inflammatory proteins such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was observed. Moreover, the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinases (ERKs), c-Jun <i>N</i>-terminal kinase (JNK), p38 MAPK (p38), and nuclear factor kappa B (NFκB) was downregulated. To conclude, we report that biorenovation-based phosphorylation of PRN improved its anti-inflammatory activity. Cell-based in vitro assays further confirmed that P4P could be applied in the development of anti-inflammatory therapeutics.Tae-Jin ParkHyehyun HongMin-Seon KimJin-Soo ParkWon-Jae ChiSeung-Young KimMDPI AGarticleprunetin 4′-<i>O</i>-phosphateprunetinanti-inflammatory activitiesbiorenovationphosphorylationMAPK signalingOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6841, p 6841 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prunetin 4′-<i>O</i>-phosphate prunetin anti-inflammatory activities biorenovation phosphorylation MAPK signaling Organic chemistry QD241-441
spellingShingle	prunetin 4′-<i>O</i>-phosphate prunetin anti-inflammatory activities biorenovation phosphorylation MAPK signaling Organic chemistry QD241-441 Tae-Jin Park Hyehyun Hong Min-Seon Kim Jin-Soo Park Won-Jae Chi Seung-Young Kim Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway
description	Biorenovation, a microbial enzyme-assisted degradation process of precursor compounds, is an effective approach to unraveling the potential bioactive properties of the derived compounds. In this study, we obtained a new compound, prunetin 4′-<i>O</i>-phosphate (P4P), through the biorenovation of prunetin (PRN), and investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. The anti-inflammatory effect of P4P was evaluated by measuring the production of prostaglandin-E<sub>2</sub> (PGE<sub>2</sub>), nitric oxide (NO), which is an inflammation-inducing factor, and related cytokines such as tumor necrosis factor-α (TNFα), interleukin-1β (IL1β), and interleukin-6 (IL6). The findings demonstrated that P4P was non-toxic to cells, and its inhibition of the secretion of NO—as well as pro-inflammatory cytokines—was concentration-dependent. A simultaneous reduction in the protein expression level of pro-inflammatory proteins such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was observed. Moreover, the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinases (ERKs), c-Jun <i>N</i>-terminal kinase (JNK), p38 MAPK (p38), and nuclear factor kappa B (NFκB) was downregulated. To conclude, we report that biorenovation-based phosphorylation of PRN improved its anti-inflammatory activity. Cell-based in vitro assays further confirmed that P4P could be applied in the development of anti-inflammatory therapeutics.
format	article
author	Tae-Jin Park Hyehyun Hong Min-Seon Kim Jin-Soo Park Won-Jae Chi Seung-Young Kim
author_facet	Tae-Jin Park Hyehyun Hong Min-Seon Kim Jin-Soo Park Won-Jae Chi Seung-Young Kim
author_sort	Tae-Jin Park
title	Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway
title_short	Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway
title_full	Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway
title_fullStr	Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway
title_full_unstemmed	Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway
title_sort	prunetin 4′-<i>o</i>-phosphate, a novel compound, in raw 264.7 macrophages exerts anti-inflammatory activity via suppression of map kinases and the nfκb pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3b40f85073d742a59dd5a83f00c4ab12
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Prunetin 4′-<i>O</i>-Phosphate, a Novel Compound, in RAW 264.7 Macrophages Exerts Anti-Inflammatory Activity via Suppression of MAP Kinases and the NFκB Pathway

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