Therapeutic effects of tripterygium glycosides on periodontitis: Exploring the role of ursolic acid and the RIPK3/NLRP3 signaling pathway.

BACKGROUND: Periodontitis, a chronic inflammatory disease, poses challenges in treatment due to its complex etiology. Tripterygium glycosides (TGs), renowned for their immunosuppressive and anti-inflammatory capabilities, present a prospective therapeutic option for the management of periodontitis. This study delves into the therapeutic efficacy of TGs in periodontitis and reveals the fundamental mechanisms involved.

MATERIALS AND METHODS: Animal experiments were conducted to observe the therapeutic effects of TGs. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to identify the optimal components. Proteomic technology was used to identify differentially expressed proteins, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking and experimental verification of core components and targets were also performed.

RESULTS: TGs markedly attenuated periodontal damage and alveolar bone resorption and significantly reduced the expression of inflammatory factors. Ursolic acid (UA) was identified as a crucial active ingredient. Among the signaling pathways, the nucleotide-binding oligomerization domain-like receptor (NLR) pathway was the most prominently enriched pathway. The binding of UA to receptor-interacting protein kinase 3 (RIPK3) was demonstrated to have therapeutic efficacy. In vitro experiments verified that UA exerts anti-inflammatory effects through the RIPK3/NLRP3 signaling pathway.

CONCLUSION: This study demonstrated that TGs effectively treat periodontitis by mitigating alveolar bone loss and suppressing inflammation. As the primary component of TGs, UA exerts therapeutic effects by inhibiting the expression of RIPK3, which in turn influences the activation of the NLRP3 inflammasome and the subsequent expression of downstream inflammatory factors. The findings of this study offer a theoretical foundation for the clinical application of TGs in the management of periodontitis.