Inhibition of Bone Resorption and Anti‐Inflammatory Effect of 7‐Hydroxycoumarin in an Animal Model of Lipopolysaccharide‐Induced Periodontal Disease

Introduction: Periodontal disease (PD) has a multifaceted etiology. The immune response to microbial invasion triggers osteoclast activation, leading to the resorption of alveolar bone and ultimately resulting in tooth loss. Objective: This study aims to investigate the anti-inflammatory properties of the bioactive compound 7-hydroxycoumarin (7HC) at concentrations of 50 and 100 mg/kg. We seek to evaluate its effectiveness in controlling alveolar bone resorption in treating PD induced by lipopolysaccharide (LPS) in an animal model. Methodology: PD was induced in C57 Bl/6 mice using a LPS injection protocol. The mice were randomly assigned to different treatment groups, receiving 7HC at 50 and 100 mg/kg, nimesulide at 25 mg/kg, and a control group that received the vehicle. Treatments were administered once daily from the 14th to the 28th day of the study. Following this treatment period, the animals were euthanized, and gingival tissue samples were collected to assess cytokine production (interleukin-1β [IL-1β] and interleukin-6 [IL-6]) using enzyme-linked immunosorbent assay (ELISA). Additionally, mRNA expression levels of matrix metalloproteinase-9 (MMP-9), TIMP-1, IL-10, and TGF-β were analyzed through qRT-PCR. The maxillae were extracted for the quantification of alveolar bone resorption by measuring the most significant distance between the cementoenamel junction and the alveolar bone crest (ABC) utilizing ImageJ software. Results: The bioactive 7HC effectively inhibited the expression of IL-1β, IL-6, and MMP-9, while simultaneously increasing the mRNA expression of IL-10 and TGF-β, cytokines recognized for their anti-inflammatory properties. Histometric analysis of the alveolar bone indicated that 7HC protects alveolar bone resorption in an animal model of PD induced by LPS injection. Conclusion: The bioactive 7HC not only inhibited proinflammatory cytokines but also stimulated the expression of the anti-inflammatory cytokine, thereby preventing bone resorption. This positions 7HC as a promising candidate for periodontal therapy.