期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 66, 期 3, 页码 571-580出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.7b03285
关键词
urolithins; microglia; neuroinflammation; ellagitannins
资金
- National Natural Science Foundation of China [31401473, 81570788, 81341102]
- Fundamental Research Funds for the Central Universities [N162004004, N130220001, N162004005, N120820002]
Emerging data suggest that urolithins, gut microbiota metabolites of ellagitannins, contribute toward multiple health benefits attributed to ellagitannin-rich foods, including walnuts, red raspberry, strawberry, and pomegranate. However, there is limited data on whether the potential neuroprotective effects of these ellagitannin-rich foods are mediated by urolithins. Herein, we evaluated the potential mechanisms of antineuroinflammatory effects of urolithins (urolithins A, B, and C; 8-methyl-O-urolithin A; and 8,9-dimethyl-O-urolithin C) in BV2 murine microglia in vitro. Nitrite analysis and qRT-PCR suggested that urolithins A and B reduced NO levels and suppressed mRNA levels of pro-inflammatory genes of TNF-alpha, IL-6, IL-1 beta, iNOS, and COX-2 in LPS-treated microglia. Western blot revealed that urolithins A and B decreased phosphorylation levels of Erk1/2, p38 MAPK, and Akt, prevented I?B-a phosphorylation and degradation, and inhibited NF-kappa B p65 subunit phosphorylation and nuclear translocation in LPS-stimulated microglia. Our results indicated that urolithins A and B attenuated LPS-induced inflammation in BV2 microglia, which may be mediated by inhibiting NF-kappa B, MAPKs (p38 and Erk1/2), and Akt signaling pathway activation. The antineuroinflammatory activities of urolithins support their role in the potential neuroprotective effects reported for ellagitannin-rich foods warranting further in vivo studies on these ellagitannin gut microbial derived metabolites.
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