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.
|Number of pages||9|
|Journal||Molecular Nutrition and Food Research|
|Early online date||27 Feb 2019|
|Publication status||Published - 1 May 2019|
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- Department of Pharmacy - Reader
- School of Applied Sciences
- Pharmacology and Therapeutics Centre - Member
- Centre for Biomarker Research - Associate Member
- Cellular and Molecular Models of Disease Centre - Affiliate Membership