ABSTRACT
Introduction: Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, causes intrauterine infection/inflammation. Offspring exposed to intrauterine infection/inflammation have an increased risk of neurological disorders, regardless of gestational age. However, the relationship between maternal periodontitis and offspring functional/histological changes in the brain has not yet been elucidated. Methods: In this study, we used a gestational mouse model to investigate the effects of maternal odontogenic infection of P. gingivalis on offspring behavior and brain tissue. Results: The step-through passive avoidance test showed that the latency of the acquisition trial was significantly shorter in the P. gingivalis group (p < 0.05), but no difference in spontaneous motor/exploratory parameters by open-field test. P. gingivalis was diffusely distributed throughout the brain, especially in the hippocampus. In the hippocampus and amygdala, the numbers of neuron cells and cyclic adenosine monophosphate response element binding protein-positive cells were significantly reduced (p < 0.05), whereas the number of ionized calcium binding adapter protein 1-positive microglia was significantly increased (p < 0.05). In the hippocampus, the number of glial fibrillary acidic protein-positive astrocytes was also significantly increased (p < 0.05). Discussion: The offspring of P. gingivalis-infected mothers have reduced cognitive function. Neurodegeneration/neuroinflammation in the hippocampus and amygdala may be caused by P. gingivalis infection, which is maternally transmitted. The importance of eliminating maternal P. gingivalis-odontogenic infection before or during gestation in maintenance healthy brain function in offspring should be addressed in near future.
ABSTRACT
Background and Aims: Equisetum arvense extract (EA) exerts various biological effects, including anti-inflammatory activity. The effect of EA on alveolar bone destruction has not been reported; therefore, we aimed to determine whether EA could inhibit alveolar bone destruction associated with periodontitis in a rat model in which periodontitis was induced using lipopolysaccharide from Escherichia coli (E. coli-LPS). Methods: Physiological saline or E. coli-LPS or E. coli-LPS/EA mixture was topically administered into the gingival sulcus of the upper molar region of the rats. After 3 days, periodontal tissues of the molar region were collected. Immunohistochemistry was performed for cathepsin K, receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG). The cathepsin K-positive osteoclasts along the alveolar bone margin were counted. EA effects on the expression of the factors regulating osteoclastogenesis in osteoblasts with E. coli-LPS-stimulation were also examined in vitro. Results: Treatment with EA significantly reduced the number of osteoclasts by decreasing the RANKL-expression and increasing OPG-expression in the periodontal ligament in the treatment group compared to the E. coli-LPS group. The in vitro study showed that the upregulation of p-IκB kinase α and ß (p-IKKα/ß), p-NF-κB p65, TNF-α, interleukin-6, and RANKL and downregulation of semaphorin 3A (Sema3A), ß-catenin, and OPG in the osteoblasts with E. coli-LPS-stimulation improved with EA-treatment. Conclusion: These findings demonstrated that topical EA suppressed alveolar bone resorption in the rat model with E. coli-LPS-induced periodontitis by maintaining a balance in RANKL/OPG ratio via the pathways of NF-κB, Wnt/ß-catenin, and Sema3A/Neuropilin-1. Therefore, EA possesses the potential to prevent bone destruction through inhibiting osteoclastogenesis attributed to cytokine burst under plaque accumulation.
ABSTRACT
Periodontal disease is the most prevalent infectious disease, and inflammatory mediators play critical roles in its progression. Therefore, controlling pro-inflammatory cytokine production, especially at initial disease stages, is essential to maintaining gingival and periodontal health. Glycyrrhizin (GL) has an anti-inflammatory effect and has been added to toothpaste and mouth rinse to prevent periodontal disease. However, there is a maximum dose for the use of GL. The aim of the present study is to screen plant extracts which can effectively enhance the effects of GL. The effects of extracts from six different plants on GL-suppressed TNF-α expression in Aggregatibacter actinomycetemcomitans (A.a.)-LPS-stimulated human oral keratinocytes (RT7) were examined. Results demonstrated that Equisetum arvense (EA) extract had the strongest additive effect on the suppression of TNF-α by GL at both mRNA and protein levels. In addition, GL downregulated the production of TNF-α by suppressing NF-κB p65 phosphorylation, but not JNK or p38 phosphorylation. In contrast, EA decreased JNK phosphorylation but not NF-κB p65 or p38 phosphorylation. The combination of GL and EA effectively attenuated A.a.-LPS-induced phosphorylation of NF-κB p65 and JNK. Furthermore, an LPS-induced periodontitis rat model showed that GL with EA supplementation significantly downregulated TNF-α mRNA in the gingival tissue. These results indicate that EA can suppress A.a.-LPS-induced pro-inflammatory cytokine production by inhibiting JNK activation and can promote the anti-inflammatory effects of GL. Our findings suggest that a combination of GL and EA may improve the development of new oral hygiene products aimed at enhancing periodontal health.
