Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke

Xu, Qingxue; Zhao, Bo; Ye, Yingze; Li, Yina; Zhang, Yonggang; Xiong, Xiaoxing; Gu, Lijuan

doi:10.1186/s12974-021-02137-8

Journal of Neuroinflammation

Table 2 Cell categories of drugs acting on and related effect/pathways after ischemic stroke

From: Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke

	Categories	Models	Effects/pathways	References
MCC950	Microglia	ICH models in mice	Inhibiting ASC oligomerization and secretion and release of Il-1β and IL-18	[166]
Parthenolide, Bay 11-7082	Macrophages	Mice BMDM (named NG5)	Inhibiting the activity of caspase-1	[167]
MNS	Macrophages	Mice BMDM	Inhibiting ASC speck formation and oligomerization	[168]
Omega-3 fatty acids	Macrophages	Mice BMDM	Inhibiting the production ofproinflammatory cytokines	[169]
Isoliquiritigenin (ILG)	Neurons	Rats model	Inhibiting NLRP3 inflammasome activation mediated by NF-κB	[78, 170]
IMM-H004	Neurons	pMCAO rats model	Anti-inflammatory pathway dependent on CKLF1	[171]
Eicosapentaenoic acid	Neurons, Microglia	MCAO mice, OGD model of BV2 cell line	Obstructing GPR40 and GPR20	[172]
Geniposide	Microglia	BV2 cell line OGD/R model	Reducing inflammatory cytokine levels; increasing the autophagic activity	[173]
Sinomenine	Astrocytes, Microglia	MCAO mice model, Astrocyte, Microglia OGD model	Inhibiting the NLRP3 inflammasome mediated by AMPK pathway	[174]
Corylin	Microglia	LPS-induced BV2 cell line inflammation	Alleviating LPS-induced inflammation	[175]
Minocycline	Microglia	tMCAO mice model; OGD/R model of BV2 cell line	Stoping microglial activation; inhibiting maturation and release of proinflammatory cytokines	[176]
Arctigenin	Neurons	MCAO rats, OGD/R neuron model	Inhibiting sirtuin-1 and decreasing activation of the NLRP3 inflammasome	[177]
Nicorandil	Microglia	OGD/R model of BV2 cell line	Opening K⁺-ATP channel; inhibiting the TLR4 signaling pathway	[178]
Curcumin	Macrophages	Mice BMDM	Stopping K⁺ efflux; inhibiting caspase-1 activation and IL-1β secretion	[179]
IVIG	Neurons, primary cortical neurons	MCAO/R mice; OGD/R model of neuron	Increasing the expression level of the antiapoptotic protein Bcl-2	[24, 180]
Aloe vera	Macrophages derived from monocytes		Inhibiting specific signal transduction pathways and proinflammatory cytokines	[181]
A151	Macrophage derived from bone marrow	BMDM OGD model	Downregulating the levels of iNOS and NLRP3 inflammasome	[182]
Chrysophanol	Neurons	tMCAO mice	Inhibiting the expression of NLRP3, caspase-1, and IL-1β	[183]
Umbelliferone	Neurons	MCAO rats	Reducing TXNIP expression	[172]
Apocynin	Neurons, Astrocytes, Microglia	MCAO/R model, astrocyte, BV2 cell line	Inhibiting the phosphorylation and degradation of IκBα and nuclear translocation of NF-κBp65	[184]
IFN-β	Neurons	tMCAO in IFN-β knockout (IFN-β KO) mice	Inhibiting the STAT1 phosphorylation	[185]
JQ1	Neurons, Astrocytes, Microglia	MCAO/R model, astrocyte, BV2 cell line	BRD4 inhibitor; inhibiting NF-κB	[186]
Meisoindigo	Neurons, Microglia	MCAO mice stroke model, OGD/R models of HT-22 and BV2 cell lines	Suppressing the TLR4/NF-κB signaling pathway	[187]
Ezetimibe	Neurons, Microglia	MCAO rats	Increasing the expression of p-AMPK, Nrf2, and Ho-1 and decreasing that of TXNIP	[188]
Edaravone	Neurons, Microglia	Rats ICH	Reducing the generation of IL-1β, caspase-1 and inhibiting NF-κB	[189]
Ginkgo diterpene lactones	Neurons, Astrocytes, Microglia	MCAO/R mice, Primary astrocyte OGD/R model	Downregulating of TLR4/NF-κB signaling	[190]
Ketone metabolite hydroxybutyrate		BMDM	Inhibiting K⁺ outflow	[191]
Probenecid	Astrocytes	Primary astrocyte OGD/R model	Pannexin 1 inhi201caspase-1 and AQP4	[192]
Nafamostat mesilate	Microglia	tMCAO rats	Inhibiting the NF-κB signaling pathway and inflammasome activation	[193]
17 β-estradiol	Neurons	MCAO/R mice	Reducing the expression of components of the NLC4 inflammasome	[194]
Procyanidins	Neurons, Microglia	OGD/R and MCAO/R rats, BV2 cell line	Inhibiting TLR4-NF-κB-NLRP3 signaling pathways	[195]
Astragaloside IV	Neurons, Microglia	tMCAO/R mice	Inhibiting TLR4 pathway; reducing ROS production	[196]
Resveratrol	Neurons	MCAO/R rats	Downregulating TXNIP expression; decreasing autophagic activity	[84, 197]
Sulforaphane	Neurons	MCAO/R rats	Inhibiting NLRP3 inflammasome activity; downregulating the expression of caspase-1, IL-18, and IL-1β	[198]

MNS, 3,4-methylenedioxy-beta-nitrostyrene; IVIG, intravenous immunoglobulin; IFN-β, interferon-β; pMCAO, permanent middle cerebral artery occlusion; tMCAO, transient middle cerebral artery occlusion; MCAO/R, middle cerebral artery occlusion/reperfusion; OGD/R, oxygen glucose deprivation/reperfusion; ICH, intracerebral hemorrhage; BMDM, bone marrow–derived Macrophages; K⁺-ATP channel, ATP-sensitive potassium channel; iNOS, inducible nitric oxide synthase; STAT1, signal transducers and activators of transcription 1; BRD4, bromodomain-containing protein 4; AQP4, aquaporin 4; CKLF1, chemokine-like factor 1; GPR40, G protein–coupled receptor 40; AMPK, adenosine monophosphate–activated protein kinase; LPS, lipopolysaccharide; TLR4, Toll-like recepetor; IL-1β, interleukin-1β; TXNIP, thioredoxin-interaction protein; NF-κB, nuclear factor kappa B; ROS, reactive oxygen species

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