Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages

The aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflam...

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Váldodahkkit: Dolores González de Llano, Mikel Roldán, Laura Parro, Begoña Bartolomé, M. Victoria Moreno-Arribas
Materiálatiipa: Artihkal
Giella:English
Almmustuhtton: MDPI AG 2023-01-01
Ráidu:Metabolites
Fáttát:
Liŋkkat:https://www.mdpi.com/2218-1989/13/1/108
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author Dolores González de Llano
Mikel Roldán
Laura Parro
Begoña Bartolomé
M. Victoria Moreno-Arribas
author_facet Dolores González de Llano
Mikel Roldán
Laura Parro
Begoña Bartolomé
M. Victoria Moreno-Arribas
author_sort Dolores González de Llano
collection DOAJ
description The aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflammation and oxidative stress. Experiments were performed on human neuronal SH-SY5Y cells stimulated with bacterial lipopolysaccharide (LPS) and <i>tert</i>-butyl hydroperoxide (<i>t</i>BHP). Anti-inflammatory activity in terms of pro-inflammatory cytokine production was also evaluated in LPS-stimulated RAW 264.7 macrophages as a reactive microglial model. Treatment of the SH-SY5Y cells with the free phenolic acids, as well as with the conjugated metabolites, at physiologically concentrations (1, 10 and 50 μM), resulted in increased cell viability of LPS- and <i>t</i>BHP-stimulated cells. Phenolic metabolites and, especially, the conjugated derivatives also protected neuronal cells through significant attenuation of inflammation by decreasing ROS levels. Furthermore, the conjugated and microbial-derived phenolic metabolites significantly inhibited the secretion of proinflammatory cytokines (TNF-α, IL-6, and IL-8) in LPS-stimulated macrophages. Among the phenolic metabolites tested, different efficacies were observed, with the glucuronide form standing out. Overall, these results suggest, for the first time, that conjugated derivatives of phenolic acids seem to be more effective at protecting neurons from inflammation damage and oxidative stress. Further in vivo studies are warranted.
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spelling doaj.art-f4756d7b089b4512a88a03a0523b51b52023-11-30T23:29:06ZengMDPI AGMetabolites2218-19892023-01-0113110810.3390/metabo13010108Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and MacrophagesDolores González de Llano0Mikel Roldán1Laura Parro2Begoña Bartolomé3M. Victoria Moreno-Arribas4Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC-UAM), C/Nicolás Cabrera 9, 28049 Madrid, SpainDepartment of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC-UAM), C/Nicolás Cabrera 9, 28049 Madrid, SpainDepartment of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC-UAM), C/Nicolás Cabrera 9, 28049 Madrid, SpainDepartment of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC-UAM), C/Nicolás Cabrera 9, 28049 Madrid, SpainDepartment of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC-UAM), C/Nicolás Cabrera 9, 28049 Madrid, SpainThe aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflammation and oxidative stress. Experiments were performed on human neuronal SH-SY5Y cells stimulated with bacterial lipopolysaccharide (LPS) and <i>tert</i>-butyl hydroperoxide (<i>t</i>BHP). Anti-inflammatory activity in terms of pro-inflammatory cytokine production was also evaluated in LPS-stimulated RAW 264.7 macrophages as a reactive microglial model. Treatment of the SH-SY5Y cells with the free phenolic acids, as well as with the conjugated metabolites, at physiologically concentrations (1, 10 and 50 μM), resulted in increased cell viability of LPS- and <i>t</i>BHP-stimulated cells. Phenolic metabolites and, especially, the conjugated derivatives also protected neuronal cells through significant attenuation of inflammation by decreasing ROS levels. Furthermore, the conjugated and microbial-derived phenolic metabolites significantly inhibited the secretion of proinflammatory cytokines (TNF-α, IL-6, and IL-8) in LPS-stimulated macrophages. Among the phenolic metabolites tested, different efficacies were observed, with the glucuronide form standing out. Overall, these results suggest, for the first time, that conjugated derivatives of phenolic acids seem to be more effective at protecting neurons from inflammation damage and oxidative stress. Further in vivo studies are warranted.https://www.mdpi.com/2218-1989/13/1/108gut phenolic acidsglucoronidessulfatesneuroprotectionanti-inflammationoxidative stress
spellingShingle Dolores González de Llano
Mikel Roldán
Laura Parro
Begoña Bartolomé
M. Victoria Moreno-Arribas
Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages
Metabolites
gut phenolic acids
glucoronides
sulfates
neuroprotection
anti-inflammation
oxidative stress
title Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages
title_full Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages
title_fullStr Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages
title_full_unstemmed Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages
title_short Activity of Microbial-Derived Phenolic Acids and Their Conjugates against LPS-Induced Damage in Neuroblastoma Cells and Macrophages
title_sort activity of microbial derived phenolic acids and their conjugates against lps induced damage in neuroblastoma cells and macrophages
topic gut phenolic acids
glucoronides
sulfates
neuroprotection
anti-inflammation
oxidative stress
url https://www.mdpi.com/2218-1989/13/1/108
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