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.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Velagapudi, R; Lepiarz, I; El-Bakoush, A; Katola, FO; Bhatia, H; Fiebich, BL; Olajide, OA

Published Date

  • May 2019

Published In

Volume / Issue

  • 63 / 10

Start / End Page

  • e1801237 -

PubMed ID

  • 30811877

Electronic International Standard Serial Number (EISSN)

  • 1613-4133

International Standard Serial Number (ISSN)

  • 1613-4125

Digital Object Identifier (DOI)

  • 10.1002/mnfr.201801237

Language

  • eng