Immunomodulatory effects of multiple traditional Chinese medicines on periodontitis: Multi-omics sequencing and network pharmacology.

BACKGROUND

Periodontitis, a prevalent oral inflammatory disorder, fundamentally arises from disrupted homeostasis between periodontal microbiota and host immunity. Our study aims to elucidate the immunoregulatory mechanisms underlying traditional Chinese medicines (TCMs) for periodontitis management.

METHODS

By integrating multiple single-cell transcriptomic datasets, a combined investigation of cellular composition, pathway activities, cell development trajectories and intercellular communication network was employed to explore the immune microenvironment in periodontitis. Then bulk-tissue transcriptomic data was included and ssGSEA, enrichment analysis, WGCNA and PPI analysis were performed to identify the hub genes that mediated immune dysregulation in periodontitis. Network pharmacology and molecular docking were utilized to construct a comprehensive medicine-ingredient-target-cell-pathway-disease network of TCMs in the treatment of periodontitis. The candidate therapeutic targets and bioactive ingredients were validated using in vitro models, clinical specimens and mass spectrometry.

RESULTS

Immune dysregulation in periodontitis arises from both hyperactivated immune cells and dysfunctional non-immune stromal cells, which was regulated by 114 hub genes. Based on these hub genes, we identified 59 bioactive compounds and 22 candidate targets of TCMs against periodontitis, all of which showed stable bindings. Experimental validation showed KDR, CASP3 and LYN significantly promoted pro-inflammatory cytokines expression and secretion, which was inhibited by kaempferol, quercetin and salvianolic acid G.

CONCLUSIONS

By integrating conventional network pharmacology with multi-omics sequencing, we found that TCMs may exert immunomodulatory effects on periodontitis through multiple ingredient-target interactions within specific cell populations.