Isoliquiritigenin alleviates P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting NF-κB/ NLRP3/GSDMD signals in human gingival fibroblasts

•LPS/ATP induced pyroptosis through activating NF-κB/NLRP3/GSDMD signals in HGFs.•Interdomain cleavage of GSDMD by caspase-1 played an important role in pyroptosis.•High levels of interleukin-1β can cause an HGF inflammatory response.•Isoliquiritigenin attenuated LPS/ATP-induced pyroptosis and the release of IL-1β. To investigate whether pyroptosis is induced by Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)/ adenosine triphosphate (ATP) through NF-κB/NLRP3/GSDMD signaling in human gingival fibroblasts (HGFs) and whether isoliquiritigenin (ISL) alleviates pyroptosis by inhibition of NF-κB/NLRP3/GSDMD signals. Periodontitis was optimally simulated using a combination of P. gingivalis-LPS and ATP. The expression levels of genes and proteins of NF-κB, NLRP3 inflammasome, GSDMD, and IL-1β was characterized by qRT-PCR, western blotting and ELISA. The 2ʹ,7ʹ‑dichlorodihydrofluorescein diacetate fluorescence probe was used to determine the intracellular ROS level. Hoechst 33342 and PI double staining, cytotoxicity assay, and caspase-1 activity assay were used to confirm the influence of ISL on pyroptosis in P. gingivalis-LPS/ATP-treated HGFs. P. gingivalis-LPS/ATP stimulation significantly promoted expression of NF-κB, the NLRP3 inflammasome, GSDMD, and IL-1β at gene and protein levels. The proportion of membrane-damaged cells, caspase-1 activity, and the release of lactate dehydrogenase (LDH) were also elevated. However, pretreatment with ISL observably suppressed these effects. P. gingivalis-LPS/ATP induced pyroptosis in HGFs by activating NF-κB/NLRP3/GSDMD signals and ISL attenuated P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting these signals. This evidence may provide a new direction for the treatment of periodontitis.