Ginsenoside Rg1/Rb1 relieves periodontitis via inhibiting IKBKG -mediated NF-κB pathway to enhance COL1A1 expression

BACKGROUND: Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis, and effective pharmacological strategies remain limited. This study evaluated whether combined ginsenoside Rg1/Rb1 protects against periodontitis and whether this protection involves IKBKG-dependent NF-κB regulation with restoration of COL1A1. METHODS: Periodontitis was induced in rats by steel-wire ligation plus Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) challenge, followed by local gingival administration of Rg1/Rb1. In parallel, Pg-LPS-stimulated human periodontal ligament stem cells (hPDLSCs) were used to model inflammation-impaired periodontal ligament stem cells, and IKBKG was knocked down to test causality. RESULTS: In vivo, Rg1/Rb1 dose-dependently attenuated periodontal inflammation and alveolar bone resorption, accompanied by reduced IL-6 and TNF-α levels, preservation of bone volume, up-regulation of IKBKG and COL1A1, and suppression of NF-κB activation. In vitro, Rg1/Rb1 preserved hPDLSC viability, restored osteogenic differentiation-related proteins (ALP, OCN, RUNX2, and COL1A1), and reduced inflammatory cytokine production. IKBKG knockdown abolished these protective effects, indicating that Rg1/Rb1 acts through IKBKG-dependent control of NF-κB signaling. CONCLUSION: Combined ginsenoside Rg1/Rb1 alleviates periodontitis by coupling anti-inflammatory activity to restoration of COL1A1 and osteogenic differentiation-related programs through IKBKG-dependent NF-κB regulation, supporting its potential as a therapeutic strategy for periodontitis.