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Acute pancreatitis (AP) is characterized by unpredictable inflammation and potentially fatal outcomes. Pyroptosis is a type of lytic cell death mediated by the pore-forming gasdermin protein that supports inflammation and organ damage by releasing proinflammatory mediators and recruiting inflammatory cells. This review aims to comprehensively evaluate the recent advances in pyroptosis as another possible pathogenesis of AP, focusing on its mechanism and medicinal potential. Our findings suggest that pyroptosis is a finely regulated process, and overactivation of pyroptosis leads to uncontrolled inflammation and exacerbates tissue damage. In AP, mitochondrial DNA, reactive oxygen species, endoplasmic reticulum stress, microRNAs, circRNAs, and free fatty acids activate NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome, caspase, or gasdermin through different pathways to initiate pyroptosis of pancreatic acinar cells or macrophages. The cascade activation of pyroptosis caused by the interaction between different cells may lead to the expansion of inflammation and damage to related organs, such as the intestine, lung, and liver, which may contribute to the progression of severe AP. Notably, some small molecules derived from plant medicines, such as emodin, saikosaponin, sinapic acid, and baicalein, or their combination of decoction, have shown outstanding effects in inhibiting pyroptosis for AP treatment. In addition, some small-molecule mimicry peptides, recombinant proteins, mesenchymal stem cells, and extracellular vesicles derived from them may bring new methods for the treatment of pyroptosis. This work highlights the critical role of pyroptosis in pancreatic inflammation and its therapeutic application, while many existing problems are also pointed out.
Wu et al. (Mon,) studied this question.