Xu Jialin, Yuan Chunhui, Wang Guihua, Luo Jiaming, Ma Hang, Xu Li, Mu Yu, Li Yuanyuan, Seeram Navindra P, Huang Xueshi, Li Liya
Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University , Shenyang 110819, People's Republic of China.
Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University , Shenyang 110819, People's Republic of China.
J Agric Food Chem. 2018 Jan 24;66(3):571-580. doi: 10.1021/acs.jafc.7b03285. Epub 2018 Jan 16.
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-α, IL-6, IL-1β, 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 IκB-α phosphorylation and degradation, and inhibited NF-κB 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-κB, 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.
新出现的数据表明，鞣花单宁的肠道微生物群代谢产物尿石素有助于富含鞣花单宁的食物（包括核桃、红树莓、草莓和石榴）带来多种健康益处。然而，关于这些富含鞣花单宁的食物的潜在神经保护作用是否由尿石素介导的数据有限。在此，我们在体外评估了尿石素（尿石素A、B和C；8-甲基-O-尿石素A；以及8,9-二甲基-O-尿石素C）在BV2小鼠小胶质细胞中抗神经炎症作用的潜在机制。亚硝酸盐分析和qRT-PCR表明，尿石素A和B降低了LPS处理的小胶质细胞中的NO水平，并抑制了TNF-α、IL-6、IL-1β、iNOS和COX-2等促炎基因的mRNA水平。蛋白质印迹显示，尿石素A和B降低了LPS刺激的小胶质细胞中Erk1/2、p38 MAPK和Akt的磷酸化水平，阻止了IκB-α的磷酸化和降解，并抑制了NF-κB p65亚基的磷酸化和核转位。我们的结果表明，尿石素A和B减轻了LPS诱导的BV2小胶质细胞炎症，这可能是通过抑制NF-κB、MAPKs（p38和Erk1/2）和Akt信号通路激活来介导的。尿石素的抗神经炎症活性支持了它们在富含鞣花单宁的食物所报道的潜在神经保护作用中的作用，这需要对这些鞣花单宁肠道微生物衍生代谢产物进行进一步的体内研究。
