Periodontal disease is a chronic inflammatory condition that destroys the tooth-supporting structures due to the host’s immune response to microbial biofilms. Traditional periodontal treatments, such as scaling and root planing, pharmacological interventions, and surgical procedures, have significant limitations, including difficulty accessing deep periodontal pockets, biofilm recolonization, and the development of antibiotic resistance. In light of these challenges, natural bioactive compounds derived from plants, herbs, and other natural sources offer a promising alternative due to their anti-inflammatory, antioxidant, antimicrobial, and tissue-regenerative properties. This review focuses on the molecular mechanisms through which bioactive compounds, such as curcumin, resveratrol, epigallocatechin gallate (EGCG), baicalin, carvacrol, berberine, essential oils, and Gum Arabic, exert therapeutic effects in periodontal disease. Bioactive compounds inhibit critical inflammatory pathways like NF-κB, JAK/STAT, and MAPK while activating protective pathways such as Nrf2/ARE, reducing cytokine production and oxidative stress. They also inhibit the activity of matrix metalloproteinases (MMPs), preventing tissue degradation and promoting healing. In addition, these compounds have demonstrated the potential to disrupt bacterial biofilms by interfering with quorum sensing, targeting bacterial cell membranes, and enhancing antibiotic efficacy.Bioactive compounds also modulate the immune system by shifting the balance from pro-inflammatory to anti-inflammatory responses and promoting efferocytosis, which helps resolve inflammation and supports tissue regeneration. However, despite the promising potential of these compounds, challenges related to their poor bioavailability, stability in the oral cavity, and the absence of large-scale clinical trials need to be addressed. Future strategies should prioritize the development of advanced delivery systems like nanoparticles and hydrogels to enhance bioavailability and sustain release, alongside long-term studies to assess the effects of these compounds in human populations. Furthermore, combining bioactive compounds with traditional treatments could provide synergistic benefits in managing periodontal disease. This review aims to explore the therapeutic potential of natural bioactive compounds in managing periodontal disease, emphasizing their molecular mechanisms of action and offering insights into their integration with conventional therapies for a more comprehensive approach to periodontal health.

Periodontal diseases, including gingivitis and periodontitis, are chronic inflammatory conditions of the teeth’ supporting structures that can lead to progressive tissue destruction and loss if left untreated. Basic treatments like scaling and root planing, alone or combined with antimicrobial agents, are the standard of care. However, with the increasing prevalence of antibiotic resistance and the need for new ideas in therapy, adjunctive treatments like ozone therapy have gained attention. Ozone (O₃), a triatomic oxygen molecule, is used because of its strong antimicrobial, anti-inflammatory, and regenerative activity and, hence, as a potential tool in periodontal therapy. This review of the use of ozone therapy in periodontal disease breaks down the multifaceted mechanism of ozone therapy, which includes the selective antimicrobial action against biofilm-associated pathogens, immunomodulatory effects on host cells, and stimulation of tissue repair. O₃ therapy disrupts microbial biofilms, enhances immune cell function, and promotes healing by activating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways that regulate oxidative stress, inflammation, and apoptosis. Additional findings include its ability to upregulate growth factors and extracellular matrix proteins, which is significant for periodontal tissue regeneration. This review also discusses the application of O₃ therapy in periodontal cell lines, emphasizing its impact on cell viability, proliferation, and differentiation. Advances in periodontal regenerative techniques, combined with the antimicrobial and healing properties of O₃, have demonstrated significant clinical benefits. Challenges, including the need for standardized dosages, effective delivery systems, and long-term studies, are also addressed to ensure safe and effective clinical integration. O₃ therapy, with its dual antimicrobial and regenerative capabilities, offers an innovative adjunctive approach to periodontal treatment. Future research focusing on optimized protocols and evidence-based guidelines is essential to fully realize its potential in enhancing periodontal health and improving patient outcomes.

Ozone (O₃) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and explores mitigation strategies using bioactive compounds and advanced delivery platforms. Two recent meta-analyses indicate that adjunctive ozone with scaling and root planing yields statistically significant reductions in probing depth and gingival inflammation, with no significant effects on bleeding on probing, plaque control, or clinical attachment level; interpretation is limited by heterogeneity of formulations, concentrations, and delivery methods. Mechanistically, ozone imposes a dose-dependent oxidative burden that depletes glutathione and inhibits glutathione peroxidase and superoxide dismutase, precipitating lipid peroxidation, mitochondrial dysfunction, ATP depletion, and PDLF apoptosis. Concurrent activation of NF-κB and upregulation of IL-6/TNF-α, together with matrix metalloproteinase-mediated extracellular matrix degradation and tissue dehydration (notably with gaseous applications), further impairs fibroblast migration, adhesion, and ECM remodeling, constraining regenerative potential. Emerging countermeasures include co-administration of polyphenols (epigallocatechin-3-gallate, resveratrol, curcumin, quercetin), coenzyme Q10, vitamin C, and hyaluronic acid to restore redox balance, stabilize mitochondria, down-modulate inflammatory cascades, and preserve ECM integrity. Nanocarrier-based platforms (nanoemulsions, polymeric nanoparticles, liposomes, hydrogels, bioadhesive films) offer controlled ozone release and co-delivery of protectants, potentially widening the therapeutic window while minimizing cytotoxicity. Overall, current evidence supports ozone as an experimental adjunct rather than a routine regenerative modality. Priority research needs include protocol standardization, dose–response definition, long-term safety, and rigorously powered randomized trials evaluating bioactive-ozone combinations and nanocarrier systems in clinically relevant periodontal endpoints.

Background: Dental anxiety is a common psychological condition that may influence patients’ perceptions of oral health and well-being. Although its association with oral health-related quality of life (OHRQoL) has been widely studied internationally, evidence from the United Arab Emirates (UAE) remains limited. Objectives: This study aimed to examine the association between dental anxiety and OHRQoL among adult patients attending an academic dental clinic in the UAE. Methods: A cross-sectional study was conducted among adult dental patients using a non-probabilistic sampling approach. Dental anxiety was assessed using the Modified Dental Anxiety Scale (MDAS), and OHRQoL was measured using the Oral Health Impact Profile-14 (OHIP-14). Descriptive statistics and nonparametric tests were used for bivariate analyses. Multiple linear regression was applied as an exploratory approach to assess adjusted associations between dental anxiety and OHRQoL after accounting for age and gender. Results: Higher dental anxiety scores were independently associated with poorer OHRQoL after adjustment for age and gender. Bivariate analyses showed no statistically significant differences in dental anxiety or OHRQoL scores between men and women; however, subgroup comparisons should be interpreted cautiously given the sample size. The findings indicate a consistent association between higher anxiety levels and greater perceived oral health impact within the study population. Conclusions: Dental anxiety was associated with impaired oral health-related quality of life among adult dental clinic attendees in the UAE. These findings reflect associations observed within a modest, non-probabilistic, cross-sectional sample and should not be interpreted as causal or generalized to the wider population. Further longitudinal and population-based studies incorporating clinical and contextual variables are needed to clarify temporal relationships and strengthen external validity.