The anti-periodontitis action of metformin via targeting NLRP3 inflammasome

•Metformin inhibited inflammatory responses induced by LPS in human periodontitis.•Metformin suppressed NLRP3 inflammasome activation.•Metformin dysregulated genes of the NF-κB and TNF-α inflammatory signaling pathways. Periodontitis is one of the most prevalent chronic inflammatory diseases causing tooth loss in patients. However, effective ways to treat periodontitis are still limited. Metformin has been suggested to have anti-inflammatory effects in the context of periodontitis, but the exact mechanisms remain largely unknown. Human periodontal ligament cells (hPDLCs) was stimulated with P. gingivalis lipopolysaccharide (LPS) to simulate the in vivo conditions that existed in periodontitis. Inflammatory responses were monitored by measuring the protein expression and secretion of the inflammatory cytokines IL-1β and IL-18. High-quality total RNA isolated from P. gingivalis LPS-treated cells along with or without metformin treatment were used for RNA sequencing and corresponding bioinformatics analysis. Metformin treatment significantly suppressed the inflammatory responses induced by P. gingivalis LPS in hPDLCs characterized by reduced production and secretion of IL-1β and IL-18. Metformin treatment also significantly reduced expression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) and caspase-1 in hPDLCs. RNA-seq analysis showed that metformin treatment altered the expression of more than 300 genes, which belongs to 14 signaling pathways including the NF-κB pathway and TNF-α pathway. Our study provided novel insights into the anti-inflammatory effects of metformin against NLRP3 inflammasome activity, which could potentially be used for the prevention and treatment of P. gingivalis-related periodontal diseases.