Table 2.

Cell categories of drugs directly and indirectly acting on and related effect on NLRP3 pathways after ischemic stroke.

Drug	Characteristic Features	Therapeutical Actions	References
Small molecules SB 203580 Bay-11-7082 U-0126 JNK Inhibitor V	→P38-MAPK inhibitor →NF-κB inhibitor →ERK inhibitor →JNK inhibitor	Neuroprotection during induced cerebral ischemia in mouse tMCAO model and primary neuron OGD reduced expression and activation of the inflammasome and decreased release of cytokines IL-18 and IL 1β	[34]
Glyburide	NLRP3 oligomerization inhibitor	In PC12 cell OGD, anti-inflammatory and anti-oxidative stress action	[121]
MCC950	NLRP3 oligomerization inhibitor	In photothrombotic ischemia mice and primary neuron OGD, hampered platelet activation/aggregation and thrombogenesis in vitro Alleviated neuronal cell apoptosis, reduced area size of cerebral ischemia, and neurological disability	[63,94,95]
β-hydroxybutyrate (BHB)	Kefflux inhibitor and ASC oligomerization inhibitor	Inhibited NLRP3 inflammasome priming process	[25]
Nuclear factor erythroid-2 related factor 2 (NRF2)	Redox-sensitive transcription factor	Suppressed ROS- and NF-kB, modulated TXNIP complex	[96]
Nitric oxide (NO)	Gas molecule	Suppressed ASC pyroptosome formation, caspase-1 and IL-1b release	[99]
IFN-α and IFN-β	Nonspecific NLRP3 inflammasome	Promoting phosphorylation of STAT1, inducting IL-10 production	[25]
Micro RNAs	Non-protein-coding RNA	Inhibited NLRP3 protein expression	[107]
Colchicine	Alkaloid	Prevents P2X7-induced pore formation and inhibits caspase-1	[108]
Probenecid	Pannexin 1 inhibitor	In primary astrocyte OGD, reduced expression levels of NLRP3 and caspase-1 and prevented the extracellular release of IL-1β death of astrocytes and increased production of ROS	[112]
Sinomenine	Natural alkaloid compound	In mouse tMCAO model and primary mixed glial cell OGD inhibited the release of NLRP3, ASC, cleaved caspase-1, and pro-inflammatory cytokines attenuation of cerebral oedema, neurological deficit, apoptosis of neurons and reduction of infarction activation of the AMPK pathway-mitigated activation of microglia and astrocytes following ischemic damage	[114]
Paeoniflorin	Natural bioactive monoterpene glucoside	In hippocampal slices, OGD diminished expression levels of NLRP3 and its downstream proteins safeguarded neuronal cell death	[122]
Resveratrol	Natural polyphenolic compound	In mouse endothelin-1-induced MCAO model, counteracted the activation of NLRP3 and the release of IL-1β and prevented the expression of TXNIP, promoting the reduction of cerebral oedema and the size of the infarcted area	[113,115]
Curcumin	Polyphenolic compound	Inhibited endoplasmic reticulum stress, suppressed TXNIP/ NLRP3 inflammasome stimulation	[115]
Ibrutinib (PCI-32765)	Bruton’s tyrosine kinase inhibitors	Decreased levels of IL-1β IL-6, IL-23A and infiltrating microglia	[116]
Minocycline	Antibiotic immunosuppressor	In mouse tMCAO model and BV2 cell OGD inhibited activation of microglia and signals 1 and 2 of NLRP3 inflammasome activation	[117]
Nafamostat mesilate	Synthetic serine protease inhibitor	In mouse tMCAO model and primary microglial culture, OGD altered expression profiles of inflammation mediators and induced expression of anti-inflammatory mediators	[118]
Necrostatin-1	Inhibitor of RIP1 kinase	inhibits inflammasome activation in murine models	[119]
Brilliant Blue G	P2X7 receptor antagonist	Attenuated caspase-3 dependent neuronal apoptosis	[120]

ASC, Apoptosis-associated speck-like protein containing a caspase-recruitment domain; BHB, β-hydroxybutyrate; IFN-β, interferon-β; IL-1β, interleukin-1β; JNK, Jun N-terminal Kinase; NF-κB, nuclear factor kappa B; NLRP3, NLR family pyrin domain containing 3; NO, nitric oxide; OGD/R, oxygen glucose deprivation/reperfusion; P2X7, P2X purinoceptor 7; RIP, Receptor interacting protein; ROS, reactive oxygen species; STAT1, signal transducers and activators of transcription 1; tMCAO, transient middle cerebral artery occlusion; TXNIP, thioredoxin-interaction protein.