scholarly journals Z-ligustilide protects BV-2 microglial cells against oxygen-glucose deprivation/reoxygenation-induced injury by inhibiting NLRP3 inflammasome activation and pyroptosis

2020 ◽  
Vol 18 ◽  
pp. 205873922093492
Author(s):  
Jia Hu ◽  
Jie Wei ◽  
Cheng Zeng ◽  
Fengqi Duan ◽  
Sijun Liu ◽  
...  
Keyword(s):  
Cell Viability ◽  
Nlrp3 Inflammasome ◽  
Glucose Deprivation ◽  
Microglial Cells ◽  
Cell Counting ◽  
Oxygen Glucose Deprivation ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Active Caspase

Z-ligustilide (LIG) is the main bioactive compound of Danggui essential oil, which was reported to exert neuroprotective and anti-inflammatory effects. However, the underlying mechanism remains largely elusive. The present study aims to investigate the effect of LIG on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury and whether Nod-like receptor protein 3 (NLRP3) inflammasome and related pyroptosis are targets for the treatment of LIG. The OGD/R model was established in BV-2 microglial cells to investigate the protective effect of LIG. Cell viability and the release of lactate dehydrogenase (LDH) were determined by cell counting assay kit 8 and the LDH release assay kit. Western blot and immunofluorescence staining were carried out to detect NLRP3 inflammasome activation and pyroptosis. Active caspase-1 and TdT-mediated dUTP nick end labeling (TUNEL) double positive cells were defined as pyroptosis population. Statistical comparison among multiple groups was carried out by one-way analysis of variance (ANOVA) followed by least significant difference (LSD) test. Compared with control cells, OGD/R impaired cell viability and induced the release of LDH in BV-2 microglial cells, which were associated with the activation of NLRP3 inflammasome as evidenced by increased expression of NLRP3 and the cleavage of caspase-1 and interleukin-1 beta (IL-1β). In parallel with NLRP3 inflammasome activation, OGD/R induced pyroptotic cell death, manifested by the cleavage of gasdermin D (GSDMD) and increased population of active caspase-1+/TUNEL+ cells. All these events were significantly attenuated by treatment with LIG, indicating that LIG significantly inhibited NLRP3 inflammasome activation and pyroptosis, and ameliorated OGD/R-induced cell injury. In conclusion, LIG protects BV-2 microglial cells against OGD/R-induced injury via inhibition of NLRP3 inflammasome and pyroptosis.

Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1

2019 ◽  
Vol 147 ◽  
pp. 104348 ◽  
Author(s):  
Jiasi Wu ◽  
Yu Luo ◽  
Qing Jiang ◽  
Sheng Li ◽  
Wenge Huang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Coptis Chinensis ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

scholarly journals The Essential Oil of Artemisia argyi H.Lév. and Vaniot Attenuates NLRP3 Inflammasome Activation in THP-1 Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Pengxiao Chen ◽  
Qi Bai ◽  
Yanting Wu ◽  
Qiongzhen Zeng ◽  
Xiaowei Song ◽  
...  
Keyword(s):  
Essential Oil ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Artemisia Argyi ◽  
Nlrp3 Inflammasome Activation ◽  
Long Time

Artemisia argyi H. Lév. and Vaniot is a traditional medical herb that has been used for a long time in China and other Asian counties. Essential oil is the main active fraction of Artemisia argyi H. Lév. and Vaniot, and its anti-inflammatory potential has been observed in vitro and in vivo. Here, we found that the essential oil of Artemisia argyi H. Lév. and Vaniot (EOAA) inhibited monosodium urate (MSU)- and nigericin-induced NLRP3 inflammasome activation. EOAA suppressed caspase-1 and IL-1β processing and pyroptosis. NF-κB p65 phosphorylation and translocation were also inhibited. In addition, EOAA suppressed nigericin-induced NLRP3 inflammasome activation without blocking ASC oligomerization, suggesting that it may inhibit NLRP3 inflammasome activation by preventing caspase-1 processing. Our study thus indicates that EOAA inhibits NLRP3 inflammasome activation and has therapeutic potential against NLRP3-driven diseases.

scholarly journals Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity

2021 ◽  
Vol 5 (5) ◽  
pp. 1523-1534
Author(s):  
Johan Courjon ◽  
Océane Dufies ◽  
Alexandre Robert ◽  
Laurent Bailly ◽  
Cédric Torre ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Myeloid Cells ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Molecular Pattern ◽  
Nlrp3 Inflammasome Activation ◽  
Healthy Donors ◽  
Activation Potential ◽  
Key Factor ◽  
Pathogen Associated Molecular Pattern

Abstract Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Psidium guajava Flavonoids Prevent NLRP3 Inflammasome Activation and Alleviate the Pancreatic Fibrosis in a Chronic Pancreatitis Mouse Model

2021 ◽  
Vol 49 (08) ◽  
pp. 2001-2015
Author(s):  
Guixian Zhang ◽  
Liming Tang ◽  
Hongbin Liu ◽  
Dawei Liu ◽  
Manxue Wang ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Psidium Guajava ◽  
Pancreatic Fibrosis ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

Chronic pancreatitis (CP) is a multifactorial, inflammatory syndrome characterized by acinar atrophy and fibrosis. Activation of NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome is a central mediator of multiple chronic inflammatory responses and chronic fibrosis including pancreatic fibrosis in CP. The Psidium guajavaleaf is widely used in traditional medicine for the treatment of chronic inflammation, but the anti-inflammatory effect of Psidium guajavaleaf on CP has not yet been revealed. In this study, we investigated whether the extract of total flavonoids from Psidium guajava leaves (TFPGL) plays a therapeutic mechanism on CP through NLRP3 inflammasome signaling pathway in a mouse CP model. The H&E and acid-Sirius red staining indicted that TFPGL attenuated the inflammatory cell infiltration and fibrosis significantly. The results of immunohistological staining, western blot and RT-qPCR showed that the expressions of NLRP3 and caspase-1 were significantly increased in the CP model group, while TFPGL significantly decreased the NLRP3 and caspase-1 expression at both the gene and protein levels. Moreover, ELISA assay was used to examine the levels of NLRP3 inflammasome target genes, such as caspase-1, IL-1[Formula: see text] and IL-18. We found that TFPGL treatment decreased the expression of caspase-1, IL-1[Formula: see text] and IL-18, which is critical for the NLRP3 inflammasome signaling pathway and inflammation response significantly. These results demonstrated that TFPGL attenuated pancreatic inflammation and fibrosis via preventing NLRP3 inflammasome activation and TFPGL can be used as a potential therapeutic agent for CP.

scholarly journals Astragaloside IV Suppresses High Glucose-Induced NLRP3 Inflammasome Activation by Inhibiting TLR4/NF-κB and CaSR

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Bin Leng ◽  
Yingjie Zhang ◽  
Xinran Liu ◽  
Zhen Zhang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Inflammasome Activation ◽  
Astragaloside Iv ◽  
Caspase 1 ◽  
Endothelial Inflammation ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

Long-term exposure to high glucose induces vascular endothelial inflammation that can result in cardiovascular disease. Astragaloside IV (As-IV) is widely used for anti-inflammatory treatment of cardiovascular diseases. However, its mechanism of action is still not fully understood. In this study, we investigated the effect of As-IV on high glucose-induced endothelial inflammation and explored its possible mechanisms. In vivo, As-IV (40 and 80 mg/kg/d) was orally administered to rats for 8 weeks after a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). In vitro, human umbilical vein endothelial cells (HUVECs) were treated with high glucose (33 mM glucose) in the presence or absence of As-IV, NPS2143 (CaSR inhibitor), BAY 11-7082 (NF-κB p65 inhibitor), and INF39 (NLRP3 inhibitor), and overexpression of CaSR was induced by infection of CaSR-overexpressing lentiviral vectors to further discuss the anti-inflammatory property of As-IV. The results showed that high glucose increased the expression of interleukin-18 (IL-18), interleukin-1β (IL-1β), NLRP3, caspase-1, and ASC, as well as the protein level of TLR4, nucleus p65, and CaSR. As-IV can reverse these changes in vivo and in vitro. Meanwhile, NPS2143, BAY 11-7082, and INF39 could significantly abolish the high glucose-enhanced NLRP3, ASC, caspase-1, IL-18, and IL-1β expression in vitro. In addition, both NPS2143 and BAY 11-7082 attenuated high glucose-induced upregulation of NLRP3, ASC, caspase-1, IL-18, and IL-1β expression. In conclusion, this study suggested that As-IV could inhibit high glucose-induced NLRP3 inflammasome activation and subsequent secretion of proinflammatory cytokines via inhibiting TLR4/NF-κB signaling pathway and CaSR, which provides new insights into the anti-inflammatory activity of As-IV.

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