Table 1.
Epigenetic treatments targeting the NLRP3 inflammasome activation.
| Drug | Cell Line/In Vivo Model | Mechanisms of Action | Ref. |
|---|---|---|---|
| Hypomethylating agents | |||
| AZA | Human chondrocytes osteoarthritis | Demethylation of CtBP1 and CtBP2 Increase of NLRP3 transcription |
[102] |
| DAC | M. tuberculosis-infected THP-1 cells | NLRP3 demethylation and expression | [69] |
| Atherosclerosis model | miR-145 demethylation and expression Downregulation of NLRP3 expression |
[96] | |
| Renal cancer cell lines | ASC demethylation | [72] | |
| Histone demethylases and deacetylases inhibitors | |||
| GSK-J4 | DSS-induced colitis model | Downregulation of Nrf2 expression Reduced NLRP3, Casp-1 and IL-1β expression |
[99] |
| SCFA (Prop/But) | PBMCs from gout patients | IL-1β transcription downregulation | [119] |
| Acute pancreatitis model | Inhibits HDAC1 and AP-1/STAT1 interaction decreasing NLRP3 activation | [129] | |
| S. typhimurium model | Increase inflammasome oligomerization | [133] | |
| Human Caco-2 cell line | Reduced ROS production. | [136] | |
| BHB | Hyperoxaluria CKD model | Caspase-1 and IL-1β downregulation | [23] |
| MSU-induced gout model | Inhibition of NF-kB phosphoirylation and NLRP3 priming and assembly. | [22] | |
| Alzheimer’s disease model | Low ASC speck and casp-1 activation | [20] | |
| Middle cerebral artery occlusion/reperfusion model | Decreased TXNIP and ROS production. | [21] | |
| Romidepsin | Palmitic acid- and MSU-treated PBMCs from healthy donors | IL-1β transcription downregulation SOCS1 upregulation |
[120] |
| Curcumin | LPS-stimulated BMDMs | NLRP3 priming and assembly inhibition | [121] |
| SAHA | Cognitive impairment model | NLRP3, caspase-1 and IL-1β downregulation | [132] |
| BET inhibitors | |||
| JQ1 | Acute gouty arthritis model | Low IL-1β levels and pyroptosis. Downregulation of NF-kB signaling. | [84] |
| Acute colon injury model induced by LPS | Inhibit NF-kB activation and NLRP3/ASC/caspase-1 expression | [85] | |
| Cerebral ischaemia-induced brain injury | Inhibit NF-kB signaling and pro-inflammatory cytokines expression | [87] | |
| Renal carcinoma cell line | Upregulation of NLRP3 inflammasome activity and pyroptosis | [88] | |
| Sirtuin activators | |||
| Resveratrol | Myocardial infarction model | Inhibits NLRP3 and caspase-1 expression Blocks NF-κB nuclear accumulation |
[127] |
| Exogenous miRNAs | |||
| miR-30e,190,7 | Parkinson’s disease model | Downregulation of inflammsome components | [91,92,93] |
| miR-495 | Lung injury model | Downregulation of NLRP3 expression | [97] |
AZA, azacytidine; DAC, decitabine; SCFA, short-chain fatty acids, BHB, beta hydroxybutyrate; MSU: monosodium urate crystals; PBMCs, peripheral blood mononuclear cells; BMDMs, bone marrow-derived macrophages; CKD, chronic kidney disease.