Tfrd Attenuates Periodontitis By Inhibiting Pi3kγ/Akt And Mechanism Study

This study aimed to investigate whether Total Flavonoids from Rhizoma Drynariae (TFRD) exert protective effects on chronic periodontitis through inhibiting the PI3Kγ/AKT signaling pathway, thereby demonstrating anti-inflammatory, antioxidant, and osteogenic-promoting properties, which may provide a theoretical basis for its clinical development. In vitro: An inflammatory osteogenic model of human periodontal stem cells (hPDLSCs) inflammatory osteogenic model was established using TNF-α and IL-1β induction. Cells were divided into normal (Nor), osteogenic (Ost), inflammatory osteogenic (Infla+Ost), and TFRD-treated inflammatory osteogenic (Infla+Ost+TFRD) groups. After 7 days of culture, osteogenic differentiation markers and PI3Kγ/AKT pathway-related protein expression were analyzed. In vivo: Wild-type (WT), PI3Kγ knockout (PI3Kγ-/-), and PI3Kγ kinase-dead (PI3KγKD/KD) mice were used to establish a periodontitis model by silk ligation. After 2 weeks, alveolar bone metabolism, inflammatory factors, oxidative stress markers, and NF-κB signaling pathway activity were evaluated. In vitro experiments demonstrated that TFRD significantly suppressed the PI3Kγ/AKT pathway, reduced inflammatory cytokine levels, alleviated oxidative stress, and enhanced osteogenic differentiation. In vivo results confirmed that PI3Kγ-/- and PI3KγKD/KD mice exhibited significantly less alveolar bone resorption, inflammatory infiltration, and oxidative damage compared to WT mice (P<0.05). TFRD exerts anti-inflammatory, antioxidant, and bone-protective effects by specifically inhibiting the PI3Kγ/AKT signaling pathway. This study provides potential therapeutic targets and theoretical support for TFRD in the treatment of chronic periodontitis.