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

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]