Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Int J Environ Res Public Health. 2020 Dec 24;18(1):68. doi: 10.3390/ijerph18010068.
Whole red raspberry polyphenols (RRW), including ellagic acid, and their gut-derived metabolite, urolithin A (UroA), attenuate inflammation and confer health benefits. Although results from recent studies indicate that polyphenols and UroA also provide neuroprotective effects, these compounds differ in their bioavailability and may, therefore, have unique effects on limiting neuroinflammation. Accordingly, we aimed to compare the neuroprotective effects of RRW and UroA on BV-2 microglia under both 3 h and 12 and 24 h inflammatory conditions. In inflammation induced by lipopolysaccharide (LPS) and ATP stimulation after 3 h, RRW and UroA suppressed pro-inflammatory cytokine gene expression and regulated the JNK/c-Jun signaling pathway. UroA also reduced inducible nitric oxide synthase gene expression and promoted M2 microglial polarization. During inflammatory conditions induced by either 12 or 24 h stimulation with LPS, UroA-but not RRW-dampened pro-inflammatory cytokine gene expression and suppressed JNK/c-Jun signaling. Taken together, these results demonstrate that RRW and its gut-derived metabolite UroA differentially regulate neuroprotective responses in microglia during 3 h versus 12 and 24 h inflammatory conditions.
全覆盆子多酚（RRW），包括鞣花酸及其肠道衍生代谢物尿石素 A（UroA），可减轻炎症并带来健康益处。尽管最近的研究结果表明多酚和 UroA 也具有神经保护作用，但这些化合物在生物利用度上存在差异，因此可能对限制神经炎症有独特的作用。因此，我们旨在比较 RRW 和 UroA 在脂多糖（LPS）和三磷酸腺苷（ATP）刺激诱导的 3 h 及 12 和 24 h 炎症条件下对 BV-2 小胶质细胞的神经保护作用。在 LPS 和 ATP 刺激诱导的 3 h 炎症中，RRW 和 UroA 抑制促炎细胞因子基因表达并调节 JNK/c-Jun 信号通路。UroA 还降低诱导型一氧化氮合酶基因表达并促进 M2 小胶质细胞极化。在 LPS 刺激诱导的 12 或 24 h 炎症条件下，UroA 而非 RRW 减弱促炎细胞因子基因表达并抑制 JNK/c-Jun 信号。综上所述，这些结果表明，RRW 及其肠道衍生代谢物 UroA 在 3 h 与 12 和 24 h 炎症条件下对小胶质细胞的神经保护反应有不同的调节作用。
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