International Institute of Nutritional Sciences and Food Safety Studies, School of Sport and Health Sciences, University of Central Lancashire, Preston, PR1 2HE, Lancashire, UK.
Brain and Behavior Centre, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston, UK.
Mol Biol Rep. 2021 Jan;48(1):147-156. doi: 10.1007/s11033-020-06024-y. Epub 2020 Dec 8.
Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer's disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.
牙龈卟啉单胞菌在宿主中引发一系列先天免疫反应，这些反应可能导致牙周炎和痴呆症（包括阿尔茨海默病）的发展。本研究旨在评估白藜芦醇在调节牙龈卟啉单胞菌脂多糖（PgLPS）诱导的神经元细胞模型代谢性炎症中的作用模式。将神经母细胞瘤细胞 IMR-32 培养至汇合后，用来自虎杖的白藜芦醇处理，同时存在或不存在 PgLPS。通过靶向转录组谱技术定量评估了 92 个基因的信使核糖核酸（mRNA）转录物的丰度，并通过 Ingenuity 通路分析确定了受影响的生化途径。基因表达分析表明，白藜芦醇下调了多个基因标志物的 mRNA，包括生长因子、转录因子、激酶、跨膜受体、细胞因子和酶，这些基因标志物在 PgLPS 处理 IMR-32 神经母细胞瘤细胞时被激活。通路分析表明，PI3K/Akt1（PI3K/Akt1）通路的激活导致活性氧（ROS）的产生，NF-κB 通路的激活导致慢性炎症反应，以及营养利用途径，这些都被白藜芦醇在 PgLPS 挑战的 IMR-32 细胞中有利地调节。本研究表明，白藜芦醇作为一种具有多种细胞内作用模式的生物活性化合物具有潜在的应用价值，进一步支持其在神经炎症性疾病中的治疗应用。
