Induction of autophagy and activation of SIRT-1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells

Ravikanth Velagapudi, Izabela Lepiarz, Abdelmeneim El-Bakoush, Folashade Katola, Harsharan S. Bhatia, Bernd L. Fiebich, Olumayokun Olajide

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Scope: Urolithin A is an anti-inflammatory and neuroprotective gut-derived metabolite from ellagitannins and ellagic acid in pomegranate, berries, and nuts. The roles of SIRT-1 and autophagy in the neuroprotective activity of urolithin A are investigated. Methods and results: Analyses of culture supernatants from lipopolysaccharide-stimulated BV2 microglia show that urolithin A (2.5–10 µm) produced significant reduction in the production of nitrite, tumor necrosis factor (TNF)-α and IL-6. The anti-inflammatory effect of the compound is reversed in the presence of sirtuin (SIRT)-1 and the autophagy inhibitors EX527 and chloroquine, respectively. Protein analyses reveal reduction in p65 and acetyl-p65 protein. Treatment of BV2 microglia with urolithin A results in increased SIRT-1 activity and nuclear protein, while induction of autophagy by the compound is demonstrated using autophagy fluorescent and autophagy LC3 HiBiT reporter assays. Viability assays reveal that urolithin A produces a neuroprotective effect in APPSwe-transfected ReNcell VM human neural cells, which is reversed in the presence of EX527 and chloroquine. Increase in both SIRT-1 and autophagic activities are also detected in these cells following treatment with urolithin A. Conclusions: It has been proposed that SIRT-1 activation and induction of autophagy are involved in the neuroprotective activity of urolithin A in brain cells.

Original languageEnglish
Article number1801237
Pages (from-to)1-9
Number of pages9
JournalMolecular Nutrition and Food Research
Volume63
Issue number10
Early online date27 Feb 2019
DOIs
Publication statusPublished - 1 May 2019

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Sirtuin 1
Punicaceae
autophagy
Autophagy
neuroglia
Microglia
stem cells
Stem Cells
metabolites
neuroprotective effect
chloroquine
Chloroquine
Anti-Inflammatory Agents
Hydrolyzable Tannins
ellagic acid
Ellagic Acid
tumor necrosis factors
nuclear proteins
assays
Nuts

Cite this

@article{561e228a8180424888e30aa62d30fa3e,
title = "Induction of autophagy and activation of SIRT-1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells",
abstract = "Scope: Urolithin A is an anti-inflammatory and neuroprotective gut-derived metabolite from ellagitannins and ellagic acid in pomegranate, berries, and nuts. The roles of SIRT-1 and autophagy in the neuroprotective activity of urolithin A are investigated. Methods and results: Analyses of culture supernatants from lipopolysaccharide-stimulated BV2 microglia show that urolithin A (2.5–10 µm) produced significant reduction in the production of nitrite, tumor necrosis factor (TNF)-α and IL-6. The anti-inflammatory effect of the compound is reversed in the presence of sirtuin (SIRT)-1 and the autophagy inhibitors EX527 and chloroquine, respectively. Protein analyses reveal reduction in p65 and acetyl-p65 protein. Treatment of BV2 microglia with urolithin A results in increased SIRT-1 activity and nuclear protein, while induction of autophagy by the compound is demonstrated using autophagy fluorescent and autophagy LC3 HiBiT reporter assays. Viability assays reveal that urolithin A produces a neuroprotective effect in APPSwe-transfected ReNcell VM human neural cells, which is reversed in the presence of EX527 and chloroquine. Increase in both SIRT-1 and autophagic activities are also detected in these cells following treatment with urolithin A. Conclusions: It has been proposed that SIRT-1 activation and induction of autophagy are involved in the neuroprotective activity of urolithin A in brain cells.",
keywords = "Urolithin A, Neuroprotective, Autophagy, SIRT-1, Microglia, 3D human neural progenitor cells, Neuroinflammation, autophagy, neuroinflammation, neuroprotective, urolithin A, microglia",
author = "Ravikanth Velagapudi and Izabela Lepiarz and Abdelmeneim El-Bakoush and Folashade Katola and Bhatia, {Harsharan S.} and Fiebich, {Bernd L.} and Olumayokun Olajide",
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volume = "63",
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journal = "Molecular Nutrition and Food Research",
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Induction of autophagy and activation of SIRT-1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells. / Velagapudi, Ravikanth; Lepiarz, Izabela; El-Bakoush, Abdelmeneim; Katola, Folashade; Bhatia, Harsharan S.; Fiebich, Bernd L.; Olajide, Olumayokun.

In: Molecular Nutrition and Food Research, Vol. 63, No. 10, 1801237, 01.05.2019, p. 1-9.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of autophagy and activation of SIRT-1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells

AU - Velagapudi, Ravikanth

AU - Lepiarz, Izabela

AU - El-Bakoush, Abdelmeneim

AU - Katola, Folashade

AU - Bhatia, Harsharan S.

AU - Fiebich, Bernd L.

AU - Olajide, Olumayokun

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Scope: Urolithin A is an anti-inflammatory and neuroprotective gut-derived metabolite from ellagitannins and ellagic acid in pomegranate, berries, and nuts. The roles of SIRT-1 and autophagy in the neuroprotective activity of urolithin A are investigated. Methods and results: Analyses of culture supernatants from lipopolysaccharide-stimulated BV2 microglia show that urolithin A (2.5–10 µm) produced significant reduction in the production of nitrite, tumor necrosis factor (TNF)-α and IL-6. The anti-inflammatory effect of the compound is reversed in the presence of sirtuin (SIRT)-1 and the autophagy inhibitors EX527 and chloroquine, respectively. Protein analyses reveal reduction in p65 and acetyl-p65 protein. Treatment of BV2 microglia with urolithin A results in increased SIRT-1 activity and nuclear protein, while induction of autophagy by the compound is demonstrated using autophagy fluorescent and autophagy LC3 HiBiT reporter assays. Viability assays reveal that urolithin A produces a neuroprotective effect in APPSwe-transfected ReNcell VM human neural cells, which is reversed in the presence of EX527 and chloroquine. Increase in both SIRT-1 and autophagic activities are also detected in these cells following treatment with urolithin A. Conclusions: It has been proposed that SIRT-1 activation and induction of autophagy are involved in the neuroprotective activity of urolithin A in brain cells.

AB - Scope: Urolithin A is an anti-inflammatory and neuroprotective gut-derived metabolite from ellagitannins and ellagic acid in pomegranate, berries, and nuts. The roles of SIRT-1 and autophagy in the neuroprotective activity of urolithin A are investigated. Methods and results: Analyses of culture supernatants from lipopolysaccharide-stimulated BV2 microglia show that urolithin A (2.5–10 µm) produced significant reduction in the production of nitrite, tumor necrosis factor (TNF)-α and IL-6. The anti-inflammatory effect of the compound is reversed in the presence of sirtuin (SIRT)-1 and the autophagy inhibitors EX527 and chloroquine, respectively. Protein analyses reveal reduction in p65 and acetyl-p65 protein. Treatment of BV2 microglia with urolithin A results in increased SIRT-1 activity and nuclear protein, while induction of autophagy by the compound is demonstrated using autophagy fluorescent and autophagy LC3 HiBiT reporter assays. Viability assays reveal that urolithin A produces a neuroprotective effect in APPSwe-transfected ReNcell VM human neural cells, which is reversed in the presence of EX527 and chloroquine. Increase in both SIRT-1 and autophagic activities are also detected in these cells following treatment with urolithin A. Conclusions: It has been proposed that SIRT-1 activation and induction of autophagy are involved in the neuroprotective activity of urolithin A in brain cells.

KW - Urolithin A

KW - Neuroprotective

KW - Autophagy

KW - SIRT-1

KW - Microglia

KW - 3D human neural progenitor cells

KW - Neuroinflammation

KW - autophagy

KW - neuroinflammation

KW - neuroprotective

KW - urolithin A

KW - microglia

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U2 - 10.1002/mnfr.201801237

DO - 10.1002/mnfr.201801237

M3 - Article

VL - 63

SP - 1

EP - 9

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - 10

M1 - 1801237

ER -