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

6 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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