An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.
An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.
复制标题
反式白藜芦醇在牙龈卟啉单胞菌脂多糖挑战神经元细胞模型中的分子作用模式的评估。
DOI：
10.1007/s11033-020-06024-y
复制
发表时间：
2021-01
影响因子：
2.8
通讯作者：
Singhrao SK
中科院分区：
文献类型：
--
作者：
Bahar B;Singhrao SK
牙龈卟啉单胞菌在宿主中引发一系列先天性免疫应答，这可能有助于牙周炎和痴呆疾病（包括阿尔茨海默病（AD））的发展。本研究旨在评估反式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中的代谢性炎症中的作用模式。在存在或不存在PgLPS的情况下，用来自虎杖的反式白藜芦醇处理汇合的IMR-32神经母细胞瘤细胞。通过靶向转录组分析技术定量评估了一组92个基因的信使核糖核酸（mRNA）转录物的丰度，并通过Inhibitity Pathway Analysis鉴定了受影响的生化途径。基因表达分析显示，反式白藜芦醇下调多个基因标记物的mRNA，包括生长因子，转录因子，激酶，跨膜受体，细胞因子和酶，否则被PgLPS处理的IMR-32神经母细胞瘤细胞激活。途径分析表明，磷酸肌醇-3-激酶/Akt 1的激活引起的细胞氧化应激，（PI 3 K/Akt 1）途径，其导致活性氧（ROS）的产生，由活化的B细胞的核因子κ-轻链增强子（NF-kB）途径和营养利用途径的活化诱导的慢性炎症反应被反式-PgLPS攻击的IMR-32细胞中的白藜芦醇。这项研究表明，反式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的潜力，进一步支持其在神经炎性疾病中的治疗应用。
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.
登录
查看更多内容
影响因子：
4.8
作者：
Harding A;Gonder U;Robinson SJ;Crean S;Singhrao SK
通讯作者：
Singhrao SK
影响因子：
13.8
作者：
Jope RS;Cheng Y;Lowell JA;Worthen RJ;Sitbon YH;Beurel E
通讯作者：
Beurel E
DOI：
10.1073/pnas.93.7.2719
发表时间：
1996-04-02
影响因子：
11.1
作者：
Hoshi, M;Takashima, A;Imahori, K
通讯作者：
Imahori, K
影响因子：
5.5
作者：
Buller, Carolyn L.;Loberg, Robert D.;Brosius, Frank C., III
通讯作者：
Brosius, Frank C., III
影响因子：
2.8
作者：
Kugaji, Manohar S.;Kumbar, Vijay M.;Diwan, Prakash V.
通讯作者：
Diwan, Prakash V.