TY - JOUR
T1 - Pomegranate ellagitannin-gut microbial-derived metabolites, urolithins, inhibit neuroinflammation in vitro
AU - DaSilva, Nicholas A.
AU - Nahar, Pragati P.
AU - Ma, Hang
AU - Eid, Aseel
AU - Wei, Zhengxi
AU - Meschwitz, Susan
AU - Zawia, Nasser H.
AU - Slitt, Angela L.
AU - Seeram, Navindra P.
N1 - Publisher Copyright:
© 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/3/4
Y1 - 2019/3/4
N2 - Objectives: Urolithins, ellagitannin-gut microbial-derived metabolites, have been reported to mediate pomegranate’s neuroprotective effects against Alzheimer’s disease (AD), but there are limited data on their effects against neuroinflammation. Herein, we: (1) evaluated whether urolithins (urolithins A and B and their methylated derivatives) attenuate neuroinflammation in murine BV-2 microglia and human SH-SY5Y neurons, and (2) evaluated hippocampus of transgenic AD (R1.40) mice administered a pomegranate extract (PE; 100 or 200 mg/kg/day for 3 weeks) for inflammatory biomarkers. Methods: Effects of urolithins (10 μM) on inflammatory biomarkers were evaluated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. In a non-contact co-culture cell model, SH-SY5Y cell viability was assessed after exposure to media collected from LPS-BV-2 cells treated with or without urolithins. Effects of urolithins on apoptosis and caspase 3/7 and 9 release from H 2 O 2 -induced oxidative stress of BV-2 and SH-SY5Y cells were assessed. Hippocampal tissues of vehicle and PE-treated transgenic R1.40 mice were evaluated for gene expression of inflammatory biomarkers by qRT-PCR. Results: Urolithins decreased media levels of nitric oxide, interleukin 6 (IL-6), prostaglandin E 2 , and tumor necrosis factor alpha from LPS-BV-2 microglia. In the co-culture cell model, media from LPS-BV-2 cells treated with urolithins preserved SH-SY5Y cell viability greater than media from cells treated without urolithins. Urolithins mitigated apoptosis and caspase 3/7 and 9 release from H 2 O 2 -induced oxidative stress of BV-2 and SH-SY5Y cells. While not statistically significant, inflammatory biomarkers (TNF-α, COX-2, IL-1, and IL-6) appeared to follow a decreasing trend in the hippocampus of high-dose PE-treated animals compared to controls. Discussion: The attenuation of neuroinflammation by urolithins may contribute, in part, toward pomegranate’s neuroprotective effects against AD.
AB - Objectives: Urolithins, ellagitannin-gut microbial-derived metabolites, have been reported to mediate pomegranate’s neuroprotective effects against Alzheimer’s disease (AD), but there are limited data on their effects against neuroinflammation. Herein, we: (1) evaluated whether urolithins (urolithins A and B and their methylated derivatives) attenuate neuroinflammation in murine BV-2 microglia and human SH-SY5Y neurons, and (2) evaluated hippocampus of transgenic AD (R1.40) mice administered a pomegranate extract (PE; 100 or 200 mg/kg/day for 3 weeks) for inflammatory biomarkers. Methods: Effects of urolithins (10 μM) on inflammatory biomarkers were evaluated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. In a non-contact co-culture cell model, SH-SY5Y cell viability was assessed after exposure to media collected from LPS-BV-2 cells treated with or without urolithins. Effects of urolithins on apoptosis and caspase 3/7 and 9 release from H 2 O 2 -induced oxidative stress of BV-2 and SH-SY5Y cells were assessed. Hippocampal tissues of vehicle and PE-treated transgenic R1.40 mice were evaluated for gene expression of inflammatory biomarkers by qRT-PCR. Results: Urolithins decreased media levels of nitric oxide, interleukin 6 (IL-6), prostaglandin E 2 , and tumor necrosis factor alpha from LPS-BV-2 microglia. In the co-culture cell model, media from LPS-BV-2 cells treated with urolithins preserved SH-SY5Y cell viability greater than media from cells treated without urolithins. Urolithins mitigated apoptosis and caspase 3/7 and 9 release from H 2 O 2 -induced oxidative stress of BV-2 and SH-SY5Y cells. While not statistically significant, inflammatory biomarkers (TNF-α, COX-2, IL-1, and IL-6) appeared to follow a decreasing trend in the hippocampus of high-dose PE-treated animals compared to controls. Discussion: The attenuation of neuroinflammation by urolithins may contribute, in part, toward pomegranate’s neuroprotective effects against AD.
KW - Gut microflora
KW - Neuroinflammation
KW - Neuroprotective
KW - Pomegranate
KW - Urolithins
UR - http://www.scopus.com/inward/record.url?scp=85027020877&partnerID=8YFLogxK
U2 - 10.1080/1028415X.2017.1360558
DO - 10.1080/1028415X.2017.1360558
M3 - Article
C2 - 28784051
AN - SCOPUS:85027020877
SN - 1028-415X
VL - 22
SP - 185
EP - 195
JO - Nutritional Neuroscience
JF - Nutritional Neuroscience
IS - 3
ER -