Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment.

Background and Objective: There is increasing interest in preventing periodontitis using natural products. The purpose of this study was to investigate the effect of Colocasia antiquorum var. esculenta (CA) varnish on the oral microbiome and alveolar bone loss in a mouse periodontitis model. Materials and Methods: Antibacterial activity against Porphyromonas gingivalis (P. gingivalis) ATCC 53978 and cell cytotoxicity using CCK-8 on L929 cells were measured. Balb/c mice were assigned into five groups (negative control, positive control, CA in drinking water, varnish, and CA varnish). P. gingivalis was administered to the mice by oral gavage three times. After sacrifice, the oral microbiome and the levels of the inflammatory cytokine IL-1β and matrix metalloproteinase-9 were analyzed. Alveolar bone loss was measured using micro-computed tomography. Results: CA extract showed an antibacterial effect against P. gingivalis (p < 0.05) and showed no cytotoxicity at that concentration (p > 0.05). Although alpha diversity of the oral microbiome did not statistically differ between the groups (p > 0.05), the relative abundance of dominant bacteria tended to be different between the groups. The inflammatory cytokine IL-1β was reduced in the CA varnish group (p < 0.05), and no difference was observed in MMP-9 expression and alveolar bone loss (p > 0.05). Conclusions: CA varnish did not affect the overall microflora and exhibited an anti-inflammatory effect, suggesting that it is possibility a suitable candidate for improving periodontitis.

This study aimed to develop and evaluate a bakuchiol-loaded thermosensitive hydrogel (BTH) as a novel local drug delivery system for the management of periodontitis. Bakuchiol, a natural phenolic compound extracted from Psoralea corylifolia, was incorporated into a hydrogel composed of poloxamers and carboxymethylcellulose. The gelation behavior, physicochemical properties, and drug release profile were analyzed. Additionally, antibacterial activity against Porphyromonas gingivalis was assessed. Cytotoxicity was evaluated in human gingival fibroblasts and RAW 264.7 cells. Anti-inflammatory effects were determined by measuring proinflammatory cytokine expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Furthermore, alveolar bone loss, cytokine expression, and histological findings were assessed in a rat model of ligature-induced periodontitis. BTH demonstrated sol–gel transition at body temperature, with sustained drug release over 15 days. Moreover, it exhibited significant antibacterial activity against P. gingivalis and was non-cytotoxic at an extract concentration of 6.25%. In vitro, it significantly downregulated inflammatory cytokines in activated macrophages. In vivo, BTH application reduced alveolar bone loss and interleukin-1β expression in gingival tissues. Histological analysis confirmed decreased inflammatory cell infiltration and alveolar bone destruction. Thus, BTH demonstrated both antibacterial and anti-inflammatory activities, exhibiting potential as a promising therapeutic strategy for localized periodontal treatment.

Apostichopus japonicus has been used both as a food and in traditional medicine. However, its anti-inflammatory effects in periodontal diseases have not been studied. We examined the anti-inflammatory properties of Apostichopus japonicus extract in RAW 264.7 cells stimulated by Porphyromonas gingivalis. The cytotoxicity of Apostichopus japonicus extract was evaluated using the MTS assay. Its effect on NO production was then measured using the NO assay. The mRNA expression of inducible nitric oxide synthase (iNOS) and the pro-inflammatory cytokines IL-1β and IL-6 were assessed using quantitative real-time PCR (qRT-PCR). Western blotting was performed to investigate the expression of regulatory proteins involved in the NF-κB and MAPK signaling pathways. Apostichopus japonicus extract significantly inhibited NO production without cytotoxicity in RAW 264.7 cells. Following Porphyromonas gingivalis stimulation, treatment with the extract decreased iNOS mRNA expression and protein levels, which are responsible for NO production. The extract also suppressed the mRNA expression of pro-inflammatory cytokines. Additionally, Apostichopus japonicus extract inhibited NF-κB activation by regulating signaling molecules such as IKK and IκBα, while also preventing the phosphorylation of MAPK, including ERK, p38, and JNK, showing anti-inflammatory potential. Therefore, it may be a promising natural candidate for the development of new preventive and therapeutic strategies for periodontitis.

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently assessed using an MTS assay. The anti-inflammatory activity of C. okamurae on Porphyromonas gingivalis (P. gingivalis)-stimulated RAW 264.7 macrophages was evaluated by measuring nitric oxide (NO) production. mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were quantified via quantitative real-time PCR (qRT-PCR). The protein expression of iNOS, p-IKKα/β, p-IκBα, and NF-κB p65 was examined using Western blot and immunofluorescence. The results demonstrated that C. okamurae extracts exhibited no cytotoxicity in RAW 264.7 macrophages at concentrations of 0.2, 2, 20, and 200 μg/mL. The extracts dose-dependently reduced NO production, downregulated mRNA levels of proinflammatory cytokines, and inhibited iNOS expression in P. gingivalis-stimulated RAW 264.7 macrophages, a model commonly used to study periodontal inflammation. Furthermore, the extracts suppressed the phosphorylation of IKKα/β and IκBα and prevented the NF-κB p65 nuclear translocation. These findings suggest that C. okamurae extracts inhibit NF-κB signaling activation triggered by the periodontal pathogen, highlighting their potential anti-inflammatory effects, relevant to periodontal disease.