scholarly journals Ellagic acid produces neuroprotection against LPS-induced dopamine neurotoxicity via the inhibition of microglial NLRP3 inflammasome activation

2019 ◽  
Author(s):  
Xue-mei He ◽  
Qiu-yu Yang ◽  
Jing-yi He ◽  
Shuo Sheng ◽  
Jing-jie Li ◽  
...  
Keyword(s):  
Cell Line ◽  
Nlrp3 Inflammasome ◽  
Ellagic Acid ◽  
Neuronal Damage ◽  
Damage Model ◽  
Neuronal Loss ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Anti Inflammatory ◽  
Signaling Activation

Abstract Background: Neuroinflammation plays a crucial role in the pathological process of Parkinson's disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasomes activation could be an important breakthrough point in PD drug therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts and other plant tissues with various anti-inflammatory and anti-oxidant properties. However, the mechanisms underlying EA-mediated anti-inflammatory and neuroprotection have not been fully elucidated. Methods: In this study, lipopolysaccharide (LPS)-induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. Furthermore, DA neuron MN 9D cell line and microglia BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism . Results: EA ameliorat ed LPS-induced DA neuronal loss in rat substantia nigra. Furtherly, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and the subsequent pro-inflammatory cytokines excretion. In addition, EA-mediated anti-neuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity was not shown upon microglial NLRP3 siRNA treatment. Conclusions: This study demonstrated EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome signaling activation.

scholarly journals Ellagic acid produces neuroprotection against LPS-induced dopamine neurotoxicity via the inhibition of microglial NLRP3 inflammasome activation

2019 ◽  
Author(s):  
Xue-mei He ◽  
Qiu-yu Yang ◽  
Jing-yi He ◽  
Shuo Sheng ◽  
Jing-jie Li ◽  
...  
Keyword(s):  
Cell Line ◽  
Nlrp3 Inflammasome ◽  
Ellagic Acid ◽  
Neuronal Damage ◽  
Damage Model ◽  
Neuronal Loss ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Anti Inflammatory ◽  
Signaling Activation

Abstract Background: Neuroinflammation plays a crucial role in the pathological process of Parkinson's disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasomes activation could be an important breakthrough point in PD drug therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts and other plant tissues with various anti-inflammatory and anti-oxidant properties. However, the mechanisms underlying EA-mediated anti-inflammatory and neuroprotection have not been fully elucidated.Methods: In this study, lipopolysaccharide (LPS)-induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. Furthermore, DA neuron MN9D cell line and microglia BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism.Results: EA ameliorated LPS-induced DA neuronal loss in rat substantia nigra. Furtherly, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and the subsequent pro-inflammatory cytokines excretion. In addition, EA-mediated anti-neuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity was not shown upon microglial NLRP3 siRNA treatment. Conclusions: This study demonstrated EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome signaling activation.

scholarly journals Ellagic acid produces neuroprotection against LPS-induced dopamine neurotoxicity via the inhibition of microglial NLRP3 inflammasome activation

2020 ◽  
Author(s):  
Xuemei He ◽  
Qiuyu Yang ◽  
Jingyi He ◽  
Shuo Sheng ◽  
Jingjie Li ◽  
...  
Keyword(s):  
Cell Line ◽  
Nlrp3 Inflammasome ◽  
Ellagic Acid ◽  
Neuronal Damage ◽  
Damage Model ◽  
Neuronal Loss ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Anti Inflammatory ◽  
Signaling Activation

Abstract Background: Neuroinflammation plays a crucial role in the pathological process of Parkinson's disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasomes activation could be an important breakthrough point in PD drug therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts and other plant tissues with various anti-inflammatory and anti-oxidant properties. However, the mechanisms underlying EA-mediated anti-inflammatory and neuroprotection have not been fully elucidated.Methods: In this study, lipopolysaccharide (LPS)-induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. Furthermore, DA neuron MN9D cell line and microglia BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism.Results: EA ameliorated LPS-induced DA neuronal loss in rat substantia nigra. Furtherly, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and the subsequent pro-inflammatory cytokines excretion. In addition, EA-mediated anti-neuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity was not shown upon microglial NLRP3 siRNA treatment.Conclusions: This study demonstrated EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome signaling activation.

scholarly journals Ellagic Acid Protects Dopamine Neurons via Inhibition of NLRP3 Inflammasome Activation in Microglia

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xue-mei He ◽  
Yan-zhen Zhou ◽  
Shuo Sheng ◽  
Jing-jie Li ◽  
Guo-qing Wang ◽  
...  
Keyword(s):  
Cell Line ◽  
Nlrp3 Inflammasome ◽  
Ellagic Acid ◽  
Neuronal Damage ◽  
Neuronal Loss ◽  
Dopamine Neurons ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Signaling Activation

Neuroinflammation plays a crucial role in the pathological process of Parkinson’s disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of the NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasome activation could be an important breakthrough point on PD therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts, and other plant tissues with anti-inflammatory, antioxidant, and neuroprotective properties. However, the mechanisms underlying EA-mediated anti-inflammation and neuroprotection have not been fully elucidated. In this study, a lipopolysaccharide- (LPS-) induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. In addition, the DA neuronal MN9D cell line and microglial BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism. Results indicated that EA ameliorated LPS-induced DA neuronal loss in the rat substantia nigra. Further, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and subsequent proinflammatory cytokines’ excretion. Second, EA-mediated antineuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity were not shown upon microglial NLRP3 siRNA treatment. In conclusion, this study demonstrated that EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome activation.

scholarly journals Coixol Suppresses NF-κB, MAPK Pathways and NLRP3 Inflammasome Activation in Lipopolysaccharide-Induced RAW 264.7 Cells

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 894 ◽  
Author(s):  
Yusheng Hu ◽  
Qilyu Zhou ◽  
Tianlong Liu ◽  
Zhongjie Liu
Keyword(s):  
Nitric Oxide ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Receptor Protein ◽  
Raw 264.7 Cells ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Coixol, a plant polyphenol extracted from coix (Coix lachryma-jobi L.var.ma-yuen Stapf), has not been investigated for its anti-inflammatory effect. In this study, using a lipopolysaccharide (LPS)-induced macrophage cell model, we observed that coixol can effectively reduce the expression of interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthases (iNOS), and cyclooxygenase (COX)-2, but had no effect on the expression of the anti-inflammatory mediator IL-10. Furthermore, we found that coixol inhibits mitogen-activated protein kinases (MAPKs), nuclear transcription factor κ B (NF-κB) pathways, and NOD-like receptor protein (NLRP) 3 inflammasome activation. In conclusion, the present study demonstrates that coixol exerts certain anti-inflammatory effects by inhibiting the expression of pro-inflammatory mediators in vitro. The mechanism of this effect was in part related to its ability to inhibit the activation of NF-κB, MAPKs pathways, and NLRP3 inflammasome.

scholarly journals Micheliolide Attenuates Lipopolysaccharide-Induced Inflammation by Modulating the mROS/NF-κB/NLRP3 Axis in Renal Tubular Epithelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xianghong Lei ◽  
Shuting Li ◽  
Congwei Luo ◽  
Yuxian Wang ◽  
Yanxia Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Tubular Epithelial Cells ◽  
Renal Inflammation ◽  
Renal Tubular Cells ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory ◽  
Renal Tubular

Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1β and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL’s anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

scholarly journals Efficacy of TSPO ligands on neuronal damage mediated by LPS-stimulated BV-2 microglial activation

2021 ◽  
Author(s):  
baoyu ma ◽  
Yongxin Liu ◽  
Xiao Zhang ◽  
Rui Zhang ◽  
Zhenjiang Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Culture System ◽  
Neuronal Damage ◽  
Pathological Process ◽  
Translocator Protein ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Neuroprotective Effects ◽  
Activated Microglia

Abstract Background Neuroinflammation mediated by microglia is an important pathological process of neurodegenerative diseases. Alleviating the inflammatory response caused by activated microglia might be a valuable treatment. The 18-kDa translocator protein (TSPO), as a marker of neuroinflammation, is significantly elevated in activated microglia. But the function of TSPO in microglia has not been well demonstrated. Methods In this study, we evaluated the role of TSPO and its ligands in LPS-activated BV-2 microglia involving mitophagy pathway and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Then, in the microglia-neuron co-culture system, the neurotoxicity induced by LPS-activated microglia and the neuroprotective effects of TSPO ligands were evaluated. Results Our results showed that after stimulated by LPS, TSPO expression was increased, meanwhile the expression of autophagy associated proteins were decreased in BV-2 microglia cells, but the reduction was reversed by pretreatment with PK11195 and Midazolam. Simultaneously, the NLRP3 inflammasome were increased in LPS activated BV-2 microglia in Transwell co-culture system, pretreatment with TSPO ligands could curb this undesirable situation. Furthermore, TSPO ligands improved the cell viability and reduced apoptosis of neuronal cells in co-culture system. Conclusions TSPO ligands PK11195 and Midazolam showed neuroprotective effects by reducing the inflammatory response of LPS-activated microglia, which may be related to the enhancement of mitophagy and the inhibition of NLRP3 inflammasome.

scholarly journals Curcumin Reduces Neuronal Loss and Inhibits the NLRP3 Inflammasome Activation in an Epileptic Rat Model

2018 ◽  
Vol 15 (3) ◽  
pp. 186-192 ◽  
Author(s):  
Qianchao He ◽  
Lingfei Jiang ◽  
Shanshan Man ◽  
Lin Wu ◽  
Yueqiang Hu ◽  
...  
Keyword(s):  
Rat Model ◽  
Nlrp3 Inflammasome ◽  
Neuronal Loss ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance

2017 ◽  
Vol 235 (3) ◽  
pp. 179-191 ◽  
Author(s):  
Tsutomu Wada ◽  
Akari Ishikawa ◽  
Eri Watanabe ◽  
Yuto Nakamura ◽  
Yusuke Aruga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
M2 Macrophage ◽  
Expression Levels ◽  
Nlrp3 Inflammasome Activation ◽  
M1 Macrophage ◽  
Anti Inflammatory

Obesity-associated activation of the renin-angiotensin-aldosterone system is implicated in the pathogenesis of insulin resistance; however, influences of mineralocorticoid receptor (MR) inhibition remain unclear. Therefore, we aimed to clarify the anti-inflammatory mechanisms of MR inhibition using eplerenone, a selective MR antagonist, in C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks. Eplerenone prevented excessive body weight gain and fat accumulation, ameliorated glucose intolerance and insulin resistance and enhanced energy metabolism. In the epididymal white adipose tissue (eWAT), eplerenone prevented obesity-induced accumulation of F4/80+CD11c+CD206−-M1-adipose tissue macrophage (ATM) and reduction of F4/80+CD11c−CD206+-M2-ATM. Interestingly, M1-macrophage exhibited lower expression levels of MR, compared with M2-macrophage, in the ATM of eWAT and in vitro-polarized bone marrow-derived macrophages (BMDM). Importantly, eplerenone and MR knockdown attenuated the increase in the expression levels of proIl1b, Il6 and Tnfa, in the eWAT and liver of HFD-fed mice and LPS-stimulated BMDM. Moreover, eplerenone suppressed IL1b secretion from eWAT of HFD-fed mice. To reveal the anti-inflammatory mechanism, we investigated the involvement of NLRP3-inflammasome activation, a key process of IL1b overproduction. Eplerenone suppressed the expression of the inflammasome components, Nlrp3 and Caspase1, in the eWAT and liver. Concerning the second triggering factors, ROS production and ATP- and nigericin-induced IL1b secretion were suppressed by eplerenone in the LPS-primed BMDM. These results indicate that eplerenone inhibited both the priming and triggering signals that promote NLRP3-inflammasome activation. Therefore, we consider MR to be a crucial target to prevent metabolic disorders by suppressing inflammasome-mediated chronic inflammation in the adipose tissue and liver under obese conditions.

scholarly journals Coenzyme Q0 Inhibits NLRP3 Inflammasome Activation through Mitophagy Induction in LPS/ATP-Stimulated Macrophages

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
You-Cheng Hseu ◽  
Yu-Fang Tseng ◽  
Sudhir Pandey ◽  
Sirjana Shrestha ◽  
Kai-Yuan Lin ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Coenzyme Q ◽  
Antioxidant Properties ◽  
Variable Number ◽  
Ros Generation ◽  
Inflammasome Activation ◽  
Raw264.7 Macrophages ◽  
Mitochondrial Ros ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

Coenzyme Q (CoQ) analogs with a variable number of isoprenoid units have exhibited as anti-inflammatory as well as antioxidant molecules. Using novel quinone derivative CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero side chain isoprenoid), we studied its molecular activities against LPS/ATP-induced inflammation and redox imbalance in murine RAW264.7 macrophages. CoQ0’s non- or subcytotoxic concentration suppressed the NLRP3 inflammasome and procaspase-1 activation, followed by downregulation of IL1β expression in LPS/ATP-stimulated RAW264.7 macrophages. Similarly, treatment of CoQ0 led to LC3-I/II accumulation and p62/SQSTM1 activation. An increase in the Beclin-1/Bcl-2 ratio and a decrease in the expression of phosphorylated PI3K/AKT, p70 S6 kinase, and mTOR showed that autophagy was activated. Besides, CoQ0 increased Parkin protein to recruit damaged mitochondria and induced mitophagy in LPS/ATP-stimulated RAW264.7 macrophages. CoQ0 inhibited LPS/ATP-stimulated ROS generation in RAW264.7 macrophages. Notably, when LPS/ATP-stimulated RAW264.7 macrophages were treated with CoQ0, Mito-TEMPO (a mitochondrial ROS inhibitor), or N-acetylcysteine (NAC, a ROS inhibitor), there was a significant reduction of LPS/ATP-stimulated NLRP3 inflammasome activation and IL1β expression. Interestingly, treatment with CoQ0 or Mito-TEMPO, but not NAC, significantly increased LPS/ATP-induced LC3-II accumulation indicating that mitophagy plays a key role in the regulation of CoQ0-inhibited NLRP3 inflammasome activation. Nrf2 knockdown significantly decreased IL1β expression in LPS/ATP-stimulated RAW264.7 macrophages suggesting that CoQ0 inhibited ROS-mediated NLRP3 inflammasome activation and IL1β expression was suppressed due to the Nrf2 activation. Hence, this study showed that CoQ0 might be a promising candidate for the therapeutics of inflammatory disorders due to its effective anti-inflammatory as well as antioxidant properties.

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