Table 1.

Role of NLRP3 in Gastrointestinal I/R Injury.

Disease	Supplementation	Human/animal study	Cell line	NLRP3 expression	Target/signaling pathway	Observation	Ref
Hepatic I/R Injury	–	C56BL/6 mice	NPCs, KCs	Up	PINK1, IL-1β, TNF-α, Caspase-1/3, p62, LC3B, Cytochrome-c, LC3B-I/II	PINK1-mediated mitophagy by decreasing NLRP3 inflammasome activity could protect against hepatic I/R injury.	(14)
	–	Male C57/BL6 Mice	BMDMs	Up	STING, TNF-α, IFN-β, IL-1β/6/18, MCP-1, CXCL-10, Caspase-1	Aging through enhancement of STING-mediated NLRP3 activation in macrophages could aggravate liver I/R injury.	(15)
	–	Male C57 Mice	Macrophage, BMDMs	–	ATP6V0D2, p62, ASC, TNF-α, IL-1β/6/10/18, LC3-I/II, Caspase-1,	Inhibition of ATP6V0D2 via impairing Notch1/Hes1 signaling by promoting NLRP3 activation could aggravate liver I/R injury.	(16)
	–	Male C57BL/6J Mice	RAW 264.7	Up	SET8, MARK4, IL-1β/18, Caspase-1	SET8 through suppression of MARK4/NLRP3 inflammasome pathway could mitigate hepatic I/R injury.	(17)
	–	C57BL/6J Mice	Hepatocyte	Up	ALT, AST, ASC, IL-1β/6, TNF-α, INF-g, Ccl2, CXCR1, CXCR2, LDH	NLRP3 could regulate neutrophil and chemokine-mediated functions and contribute to hepatic I/R injury, independently of the inflammasome.	(18)
	Morin (MRN)	Male SD Rats; treated with 50 and 100 mg/kg MRN, orally, daily, for 10 days	–	Up	Nrf2, TLR4, TNF-α, IL-1β/6, MDA, MPO, TAC, Bax, Caspase-3	Morin via downregulating NLRP3 could alleviate hepatic I/R injury.	(22)
		Male C57BL/6J Mice	RAW 264.7	Up	CMPK2, AIM2, IL-18, IL-1β, TNF-α, Caspase-1, ALT, AST	CMPK2 via the NLRP3 signaling pathway could accelerate liver I/R.	(23)
	Octreotide (OTC), Melatonin (MLT)	Male Albino Rats; treated with 50 and 75 μg/kg, IP, SC, 0.5 h before the beginning of ischemia surgery, MLT 10 mg/kg prior to ischemia and again directly prior to reperfusion	–	Up	TLR-4/6, NF-κB p65, Bcl-2, Bax, Cytochrome-c, Caspase-1/9, HMGB-1	OTC and MLT through inhibition of TLR4/NF-κB/NLRP3 pathway could alleviate inflammasome-induced pyroptosis in hepatic I/R injury.	(24)
	Fisetin	Male C57BL/6J Mice; treated with 5, 10, and 20 mg/kg Fisetin, IP, 0.5 h before portal and artery hepatic occlusion	RAW264.7; 2.5, 5, 10 μmol/L fisetin during H/R	Up	GSK-3β, AMPK, TNF-α, IL-1β/18, Caspase-1, ALT, AST	Fisetin by regulating GSK-3β/AMPK/NLRP3 inflammasome pathway could mitigate hepatic I/R.	(25)
Intestinal I/R Injury	–	C57BL/6J Mice, 6 intestinal ischemia patients and 6 healthy control group	LVECs	Up	IL-1β, IL-18, IL-6, TNF-α, Caspase-1/3, E-cadherin	Activation of NLRP3 inflammasome in lung endothelial cells could contribute to intestinal I/R induced acute lung injury.	(19)
	Metformin	C57BL/6 mice; treated with 20 and 40 mg/kg metformin, IP, at the beginning of reperfusion, then applied an optimum I/R injury model	Caco-2; 1-2 mM for 30 min	Up	TXNIP, GSDMD, I-FABP, TER, ZO-1, Occludin, LDH, IL-1β/6, TNF-α	Metformin via the TXNIP-NLRP3-GSDMD pathway could protect against intestinal I/R injury and cell pyroptosis.	(20)
	Rapamycin (RAP), Chloroquine (CQ)	Male C57BL/6 Mice; received 3 mg/kg RAP and 60 mg/kg CQ, IP, 1 h prior to ischemia	Caco-2; 20 µmol/L CQ	Up	TNF-α, IL-6, IL-1β, Caspase-1, ASC, p62, LC3-I/II, Beclin-1	Autophagy induction via inhibiting NLRP3 inflammasome activation could ameliorate inflammatory responses in intestinal I/R injury.	(21)