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Submitted:
07 December 2023
Posted:
08 December 2023
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Agents | Targets | Experimental model and mechanism | Diseases | References | ||
---|---|---|---|---|---|---|
Small molecule inhibitors | ||||||
MCC950 | The NACHT domain of NLRP3 inflammasome | Block ASC oligomerization, inhibit inflammation (1) Reduce synovitis and cartilage erosion by inhibiting NLRP3 and caspae-1 activation in CIA model. (2) Elevated liver enzymes in phase II clinical trial. | RA, ASCVD, OP, ILD | [126,127,131,132] | ||
VX-765 | Caspase-1 | Ameliorate the severity and progression of synovitis in CIA murine model. | RA, ASCVD | [128,133] | ||
Disulfiram | GSDMD | Inhibits pyroptosis and inflammatory cytokine release in both canonical and noncanonical inflammasome pathways. | RA and associated OP | [129] | ||
IL-18BP | IL-18 binding protein | Reduces Th17 cells with resultant inhibition of osteoclastogenesis and induces osteoblasts formation. | RA and associated OP | [134] | ||
Natural products | ||||||
Celastrol (isolated from Tripterygium wilfordii) | Inhibit the ROS-NF-κB-NLRP3 inflammasome axis. |
|
RA | [135,136] | ||
Baihu-Guizhi decoction (BHGZD) | Inhibit TLR4/NF-κB/NLRP3 activation- induced pyroptosis. | Reduce synovitis as well as bone erosion and alleviate disease activity through inhibiting NF-κB via TLR4/PI3K/AKT signaling to suppress the NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in AIA-modified rat model | RA | [138] | ||
Sulforaphene (extracted from radish seeds) | NLRP3 | Suppress the M1 polarization of macrophages and reduce synovitis in CIA murine model | RA | [139] | ||
Osthole (extracted from Angelicae pubescentis radix) | AMPK agonist | Inhibit NLRP3 inflammasome activation by regulating mitochondrial homeostasis in CIA rat model. | RA | [141] | ||
Scropolioside B (isolated from Scrophularia dentada Royle ex Benth.) | NF-κB and the NLRP3 inflammasome pathway | Inhibit NF-κB activity, reduce NLRP3 expression, and suppress the maturation as well as the release of IL-1β. | RA and associated atherosclerosis | [142] | ||
Wedelolactone, derived from Eclipta alba | NF-κB and the NLRP3 inflammasome | Ameliorate synovitis and cardiac complications via inhibiting the activation of NF-κB/NLRP3 inflammasome pathway | RA and cardiac complication | [143] | ||
Disease-modifying anti-rheumatic drugs (DMARDs) | ||||||
Hydroxychloroquine or chloroquine | The second signal of NLRP3 activation |
|
RA and associated ASCVD | [144,145] | ||
Anakinra, a biological DMARDs | IL-1β receptor antagonist | Inhibit the NLRP3 inflammasome downstream cytokine, IL-1β, in RA patients. | RA | [146] | ||
Canakinumab, a biological DMARDs | Monoclonal antibody targeting IL-1β | Reduce the rates of recurrent ASCVD, including myocardial infarction and stroke | RA and associated ASCVD | [147] | ||
Tofacitinib, a Janus kinase 1/3 inhibitor | NLRP3 inflammasome | Restore the balance of γδTreg/γδT17 cells by inhibiting NLRP3 inflammasome in CIA model | RA | [148] | ||
Epigenetic regulators | ||||||
MiRNA-33 inhibitor | NLRP3 and caspase-1 | MiR-33 impairs mitochondrial oxygen consumption rate with increasing ROS, and then upregulates NLRP3 inflammasome expression in macrophages in CIA mice model | RA | [153] | ||
MiRNA-30a | NLRP3 | MiRNA-30a inhibits the NLRP3 inflammasome activation, reduce synovitis, and bone damage in TNFα-transgenic C57BL/6 mice model. | RA | [154] | ||
MiRNA-223 | NLRP3 | MiRNA-223 from BMSCs-derived exosomes inhibits NLRP3 activation and the release of IL-β, TNF-α, and IL-18 in RAW264.7 cells by luciferase reporter assay & rescue experiment | RA and associated ASCVD | [155] | ||
LncRNA MIAT | IL-1β | LncRNA MIAT inhibited the expression of IL-1β, TNF-α and suppressed macrophage inflammation in J774A.1 cell-based assay. | RA | [160] | ||
Allogenic mesenchymal stem cells | ||||||
hUCB-MSCs | NLRP3 inflammasome | Downregulate the activation of NLRP3 inflammasome via a paracrine loop of IL-1β signaling in CIA murine model. | RA | [162] |
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