Computational analysis of curcumin‐mediated alleviation of inflammation in periodontitis patients with experimental validation in mice

Abstract

AbstractAimUsing network pharmacology and experimental validation to explore the therapeutic efficacy and mechanism of curcumin (Cur) in periodontitis treatment.Materials and MethodsNetwork pharmacology was utilized to predict target gene interactions of Cur‐Periodontitis. Molecular docking was used to investigate the binding affinity of Cur for the predicted targets. A mouse model with ligature‐induced periodontitis (LIP) was used to verify the therapeutic effect of Cur. Microcomputed tomography (micro‐CT) was used to evaluate alveolar bone resorption, while western blotting, haematoxylin–eosin staining and immunohistochemistry were used to analyse the change in immunopathology. SYTOX Green staining was used to assess the in vitro effect of Cur in a mouse bone marrow‐isolated neutrophil model exposed to lipopolysaccharide.ResultsNetwork pharmacology identified 114 potential target genes. Enrichment analysis showed that Cur can modulate the production of neutrophil extracellular traps (NETs). Molecular docking experiments suggested that Cur effectively binds to neutrophil elastase (ELANE), peptidylarginine deiminase 4 (PAD4) and cathepsin G, three enzymes involved in NETs. In LIP mice, Cur alleviated alveolar bone resorption and reduced the expression of ELANE and PAD4 in a time‐dependent but dose‐independent manner. Cur can directly inhibit NET formation in the cell model.ConclusionsOur research suggested that Cur may alleviate experimental periodontitis by inhibiting NET formation.