Abstract:Objective: To investigate the effects of geniposide (GNP) on inflammatory damage in periodontitis rats and its potential mechanism. Methods: Rats were randomly divided into the control group, periodontitis model group (model group), periodontitis model + low-dose GNP treatment group (low-dose group), periodontitis model + medium-dose GNP treatment group (medium-dose group), periodontitis model + high-dose GNP treatment group (high-dose group), and positive control sub-antibacterial doxycycline treatment group (SDD group). High-resolution micro-CT was used to detect alveolar bone microstructure, hematoxylin-eosin (HE) staining was used to observe periodontitis histopathology, ELISA kits were used to detect serum IL-1β and IL-6 levels, and Western blotting was performed to detect protein expression of NF-κB P65, NLRP3, ASC, caspase-1, cleaved-caspase-1, and IL-1β in periodontal tissue. Results: Compared with the control group, the model group showed significantly decreased alveolar bone density (BMD) and bone volume fraction (BV/TV), while IL-1, IL-6 levels, alveolar bone resorption, and protein expressions of NF-κB P65, NLRP3, ASC, cleaved-caspase-1, and IL-1β in periodontal tissue were significantly increased (P<0.05). Meanwhile, alveolar bone resorption was significant, the alveolar ridge disappeared, and inflammatory cell infiltration was observed in periodontal tissue. Compared with the model group, the low-dose, medium-dose, high-dose, and SDD groups showed significant increases in BMD and BV/TV, and decreases in IL-1, IL-6 levels, alveolar bone resorption, and protein expressions of NF-κB P65, NLRP3, ASC, cleaved-caspase-1, and IL-1β in periodontal tissue (P<0.05). With increasing doses of GNP, the adverse changes were alleviated, alveolar bone resorption was progressively reduced, and inflammatory cell infiltration in periodontal tissue decreased. Compared with the low-dose group, the medium-dose, high-dose, and SDD groups showed significant increases in BMD and BV/TV, and decreases in IL-1, IL-6 levels, alveolar bone resorption, and protein expressions of NF-κB P65, NLRP3, ASC, cleaved-caspase-1, and IL-1β (P<0.05). Compared with the medium-dose group, the high-dose group and SDD group showed significant increases in BMD and BV/TV, and decreases in IL-1, IL-6 levels, alveolar bone resorption, and protein expressions of NF-κB P65, NLRP3, ASC, cleaved-caspase-1, and IL-1β (P<0.05). No significant difference was observed between the high-dose group and SDD group regarding BMD, BV/TV, IL-1, IL-6 levels, alveolar bone resorption, and protein expression of NF-κB P65, NLRP3, ASC, IL-1, and cleaved-caspase-1. Conclusions: Geniposide may alleviate the inflammatory response in periodontitis rats and improve alveolar bone resorption by inhibiting the activation of NF-κB/NLRP3 and suppressing IL-1β secretion.
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