Table 3.
Mechanisms of pyroptosis in inflammatory bowel diseases, colorectal cancer, and intestinal injury.
| Compound/Target | Model | Effect | Mechanism | Ref. |
|---|---|---|---|---|
| NR4A1 | Marrow-derived macrophages (BMDMs)from WT mice and NR4A1−/− mice | Inhibition | NR4A1 inhabits pyroptosis by transcriptionally inhibiting NLRP3 and IL-1β and colocalizing with NLRP3 in trans-Golgi to alleviate pathogenic bacteria-induced colitis. | [131] |
| NEK7 | MODE-K cells; DSS-induced colitis mice | Induction | NEK7 interacts with NLRP3 to regulate pyroptosis in IBD via NF-κB signaling | [132] |
| JQ1 | LPS-induced endotoxemia mice | Inhibition | JQ1 blocks inflammatory pyroptosis-related acute colon injury induced by LPS. | [133] |
| hucMSC-derived exosomes | DSS-induced colitis mice | Inhibition | hucMSC-derived exosomes attenuate colitis by modulating macrophage pyroptosis via the miR–378a–5p–NLRP3 axis. | [134] |
| SDG | HCT116 cells | Induction | SDG induces pyroptosis by activating caspase-1 to cleave GSDMD in CRC cells. | [136] |
| Nanostructured toxins | CRC samples from patients | Induction | Nanostructured toxins for the selective destruction of drug-resistant human CXCR4(+) colorectal cancer stem cells. | [137] |
| GW4064 | HT-29, SW480/HCT1 16/CACO-2/RKO cells | Induction | GW4064 enhances the chemosensitivity of colorectal cancer to oxaliplatin by inducing pyroptosis. | [142] |
| A438079 | HCT-116/SW620 cells; xenografted mice | Induction | A438079 affects CRC cell proliferation, migration, apoptosis, and pyroptosis by inhibiting the P2X7 receptor. | [143] |
| Metformin | I/R mice; Caco-2 cells | Inhibition | Metformin treatment protects gut barrier function from intestinal I/R injury and reduces oxidative stress and inflammatory responses by modulating pyroptosis. | [145] |
| CB2 receptor | LPS induced-sepsis mice | Inhibition | CB2 receptor activation plays a protective role in sepsis-induced intestinal injury by inhibiting pyroptosis. | [146] |
| Berberine | DSS-induced colitis mouse; Caco-2 cells | Inhibition | Berberine negatively regulates the Wnt/β-catenin pathway, thereby attenuating colitis-stimulated pyroptosis and intestinal mucosal barrier defects. | [148] |
| GSDME | CT26 cells; GSDME-KO CT26 cells | Induction | GSDME enhances radiation-induced pyroptosis in CRC cells and normal epithelial cells via a caspase-3-dependent pathway. | [151] |
| Dopamine-derived nanoparticles | X-ray-induced mice | Inhibition | PDA-NPs inhibit pyroptosis and alleviate ionizing radiation-induced intestinal damage. | [152] |
| p-Coumaric acid | X-ray-induced mice | Inhibition | p-Coumaric acid (CA) ameliorates ionizing radiation-induced intestinal damage by modulating oxidative stress, inflammation, and pyroptosis. | [153] |