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Table 2 Potential therapy targets of the NLRP3 inflammasome in stroke and type 2 diabetes

From: NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes

  Animal model/patient Proposed mechanism Outcomes References
MCC950 In mice in vivo and human cells ex vivo; pig model of myocardial infarction Selective inhibition of NLRP3 inflammasome activation; dose-dependently inhibited IL-1β The amount of CASP1 (an auto-processed fragment of CASP1) is dose-dependently reduced in supernatants from MCC950-treated BMDM and PBMC; infarct size as a percentage of the area at risk is significantly lower in both treatment groups compared with the control group. [63, 64]
Glyburide Patients with FCAS; P2X7¯/¯ mice Inhibit ATP-sensitive K+ channels; downstream of P2X7 Glyburide blocks the rapid, CASP1-dependent cell death that occurs when BMDMs are treated with LPS and ATP. [65]
IVIG Mouse model of focal ischemic stroke Downregulation of the pro-inflammatory cytokines IL-1β and IL-18; upregulation of Bcl-2 Administration of IVIG to mice subjected to experimental stroke significantly reduces brain infarct size and eliminates mortality; IVIG significantly decreases GD-induced neuronal cell death. [66, 67]
Anakinra Diabetic patients IL-1 receptor antagonist Proinsulin-to-insulin ratio was lower in anakinra-treated patients cf. placebo-treated patients. [68, 69]
Parthenolide and Bay 11-7082 NLRP3¯/¯ macrophages Inhibits ATPase activity of NLRP3 Blocking macrophage cell death in a dose-dependent manner. [70]
MNS WT, Syk¯/¯ mice Inhibits NLRP3 ATPase activity MNS inhibits the production of mature IL-1β in the cell supernatant as shown by immunoblotting. [71]
Omega-3 fatty acids HFD-treated mice, NLRP3¯/¯mice Blocking metabolic stress-induced NLRP3 inflammasome activation Reduces fasted glucose concentrations and improves glucose tolerance and insulin sensitivity. [72]
NaB Diabetic db/db mice Inhibits NLRP3 inflammasome pathway Improves glucose control and decreases the protein levels of NLRP3 & IL-1β. [73]
γT3 Diabetic db/db mice Blocking of NLRP3 inflammasome priming and activation γT3 preserves insulin sensitivity and ameliorates the progression of type 2 diabetes. [74]
ILG H-treated mice Inhibits NLRP3 inflammasome activation ILG attenuates HFD-induced obesity, hypercholesterolemia, and insulin resistance. [75]
RSV T2DM rat model Inhibits the activation of NLRP3 inflammasome via TXNIP Alleviates DM-induced left-ventricular dysfunction and myocardial remodeling by inhibiting NLRP3. [76]
A151 Rat model of SHR-SP Reduces the maturation of IL-1β and CASP1 and exp of NLRP3 and iNOS in response to LPS and OGD stimulation A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone pMCAO. [77]
Chrysophanol tMACO mouse model Suppresses exp of NLRP3, CASP1, and IL-β Reduces neurological deficits, infarct volume, and brain edema and ameliorates BBB permeability. [78]
GSPB2 Diabetic db/db mice Suppresses the upregulation of NLRP3 Notably attenuates levels of IL-1β and NLRP3 increased in a diabetic pancreas. [79]
UMB MCAO rat model Reduces exp of TXNIP UMB reduces the infarct volume and attenuated the production of IL-β and IL-18 by suppressing the exp of NLRP3 inflammasome. [80]
Sinomenine MCAO/R mouse model Inhibits AMPK-mediated NLRP3 inflammasome activation SINO reduces neuronal loss and attenuates the release of inflammatory cytokines after MCAO. [81]
NADPH+ apocynin MCAO/R mouse model Inhibits activation of pro-inflammatory transcription factors NF-κB and its down-stream NLRP3 inflammasome pathway NADPH and apocynin significantly reduce infarct volume, improve post-stroke survival, and recovery of neurological functions in MCAO/R mouse model. [82]
  1. BMDM bone marrow-derived macrophage, CASP1 caspase 1, exp expression, FCAS familial cold autoinflammatory syndrome, γT3 gamma-tocotrienol, GSPB2 grape seed procyanidin B2, HFD high-fat diet, ILG isoliquiritigenin, IVIG intravenous immunoglobulin, MCAO middle cerebral artery occlusion, MNS 3,4-methylenedioxy-β-nitrostyrene, NaB sodium butyrate, PBMC peripheral blood mononuclear cell, RSV rosuvastatin, SHR-SP stroke-prone spontaneously hypertensive, UMB umbelliferone, WT wild type