Panax notoginseng saponins alleviate alveolar bone loss and reprogram macrophages in diabetic periodontitis rats

Diabetic periodontitis (DP) features accelerated alveolar bone destruction driven by impaired immune regulation and compromised bone metabolism. Objective This study investigated the therapeutic potential of Panax notoginseng saponins (PNS) against alveolar bone loss in a rat DP model and elucidated its mechanisms of action. Methodology Male Sprague-Dawley rats were allocated to four groups: control, periodontitis control (CP), diabetic periodontitis (DP), and DP + PNS (80 mg/kg/day). Diabetes was induced by streptozotocin injection, followed by ligature-induced periodontitis at the maxillary first molar. After 4 weeks of PNS treatment, alveolar bone samples were analyzed by micro-CT, histomorphometry, immunohistochemistry, and immunofluorescence. Results Micro-CT and H&E analyses revealed severe alveolar bone resorption in DP rats, whereas PNS treatment substantially mitigated these destructive changes. TRAP staining demonstrated that PNS significantly suppressed osteoclast formation and activity. Immunohistochemistry detected upregulated expression of OCN in PNS-treated groups, indicating enhanced osteogenic differentiation. Immunofluorescence analysis showed that PNS promoted a phenotypic shift in macrophages, reducing pro-inflammatory M1 polarization (iNOS+) while increasing anti-inflammatory M2 populations (Arg-1+). This shift correlated with decreased interleukin-6 (IL-6) and elevated interleukin-10 (IL-10) levels. Conclusions PNS attenuates alveolar bone loss in diabetic periodontitis by inhibiting osteoclastogenesis, stimulating osteogenic activity, and modulating macrophage polarization toward an anti-inflammatory M2 phenotype. These actions collectively reduce inflammation and promote tissue regeneration, highlighting PNS as a promising candidate for managing DP-related bone destruction.