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Periodontitis Continuum: Antecedents, Triggers, Mediators, and Treatment Strategies
Abstract
Periodontitis (PD) is a chronic inflammatory disease of the periodontium characterized by the formation of gingival pockets and gingival recession. The local inflammatory environment can lead to the destruction of the extracellular matrix and subsequent bone loss. The pathophysiology of PD involves interactions between genetic predisposition, lifestyle, and environmental factors, the oral microbiota condition, systemic health disorders, innate and adaptive immune responses, and various host defenses. The review highlighted the importance of the oral cavity condition in systemic health.Thus, a correlation betweenharmful oral microbiota and cardiovascular disease (CVD)/diabetes/ arthritis, etc, progressions through inflammation and bacterial translocation was highlighted. Antecedents increase an individual's risk of developing PD, trigger initiate microbe- host immunologic responses, and mediators sustain inflammatory interactions. Generally, this review explores the antecedents, triggers, and mediators along the pathophysiological continuum of PD. An analysis of modern approaches to treating periodontitis, including antibiotics for systemic and local use, was carried out.The potential role of natural ingredients such as herbal extracts, phytoconstituents, propolis, and probiotics in preventing and treating PD was highlighted.
... Periodontitis is a multifaceted disease that affects the supporting structures of teeth, with implications extending beyond oral health to systemic conditions, such as cardiovascular disease and metabolic disturbances [7]. Despite extensive research, the intricate biochemical and cellular mechanisms underlying periodontitis remain partially understood, especially in cases where periodontal pathology is compounded by additional nutritional deficiencies [4,8]. Addressing this gap, experimental models have been instrumental in exploring the effects of periodontitis, facilitating the identification of key biochemical markers and potential therapeutic targets. ...
... Alkaline and acid phosphatases, key enzymes involved in bone metabolism, serve as vital indicators of bone formation and resorption processes, respectively [8]. Previous studies have highlighted the significance of these markers in distinguishing osteoblastic and osteoclastic activities in periodontitis, though investigations combining these markers with nutritional deficiency remain limited [4,6,9]. Understanding these dynamics is critical, as the delicate balance between bone resorption and formation directly influences the integrity of periodontal tissue, which is essential for preventing progressive bone loss and supporting long-term periodontal health. ...
... This outcome corresponds with previous studies indicating that targeted therapies can mitigate the impact of periodontitis by fostering a more favourable biochemical environment for bone preservation and regeneration. Additionally, the observed improvement in mineralization index with TPC treatment highlights the potential of complex therapeutic approaches to support osteoblastic function, a finding that resonates with the efficacy of similar interventions reported in the literature [4,9,10]. Given the multifactorial nature of periodontitis, which involves an interplay of microbial infection, host immune response, oxidative stress, and nutritional status, further research should aim to explore the long-term effectiveness of TPCs in diverse pathological contexts. ...
... Periodontitis is a multifactorial inflammatory disease that affects the supporting structures of the teeth, ultimately resulting in alveolar bone loss if left untreated [6,9]. Recent studies emphasize that both local and systemic factors contribute significantly to periodontal tissue destruction, with an increasing focus on the role of oxidative stress, nutritional deficiencies, and shifts in microbiota composition [8,10,12]. ...
... The balance between connective tissue synthesis and destruction shifts toward its breakdown first, due to the suppression of fibroblast function and, second, owing to the heightened activity of macrophages, which are capable of destroying the body's own cells [1]. The findings of this study align with previous reports on the multifactorial nature of periodontitis, especially regarding the roles of oxidative stress and nutritional deficits in exacerbating alveolar bone loss [6,9]. Other investigations have likewise highlighted that insufficient intake of key nutrients disrupts collagen synthesis and hampers bone remodeling, mirroring the protein deficiency effects observed here [11]. ...
... Mechanical therapy is the most important oral procedure to be performed in treating periodontitis [29]. In clinical practice, systemic or local drugs are also applied to treat the lesion that cannot be reached by mechanical treatment, inhibiting the immune response induced by dental plaque microorganisms, relieving infammatory response, and promoting wound healing [30]. Te main drug in periodontitis treatment is antibiotic. ...
Objective: To investigate the anti-inflammatory and bacteriostatic effects of hydrogen-rich water (HRW) intake on Wistar rats with periodontitis.
Methods: The periodontitis model of rats was established by silk ligature and Porphyromonas gingivalis (Pg) solution smearing. The rats were divided into normal control group, model group, and HRW group. The rats in normal control group were given normal feeding without any intervention, while periodontitis was induced in the rats of model group and HRW group, and the rats were given HRW intake and normal saline, respectively, during the whole procedure of the experiments. The antibacterial effect and clinical symptoms (plaque index and gingival sulcus bleeding index (SBI)) were then observed, and peripheral blood (PB), gingival sulcus fluid, and jaw samples were collected to evaluate the changes of inflammatory factors and the curative effect.
Results: In the rats of model group, alveolar bone resorption was obvious, which indicated that the rats with periodontitis were successfully constructed, and HRW intake mitigated it. Pg colony number of the rats fed with HRW was significantly lower than that of the model rats. The contents of proinflammatory factors tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in PB serum and gingival crevicular fluid (GCF) of rats in model group were significantly increased, and HRW intake reversed these and promoted the level of anti-inflammatory factor interleukin-10 (IL-10).
Conclusion: HRW can effectively inhibit the growth of periodontal pathogens and reduce inflammation and may be used to prevent or ameliorate periodontitis.
Background: Carotenoids are bioactive tetraterpenoid C40 pigments that are actively synthesized by plants, bacteria, and fungi. Compounds such as α-carotene, β-carotene, lycopene, lutein, astaxanthin, β-cryptoxanthin, fucoxanthin, and zeaxanthin have attracted increasing attention for their antiaging properties. They exhibit antioxidant, neuroprotective, and anti-inflammatory properties, contributing to the prevention and treatment of age-related diseases. Objectives: The aim of this study was to comprehensively analyze the pharmacological potential and biological mechanisms of carotenoids associated with age-related disorders and to evaluate their application in nutraceuticals, pharmaceuticals, and cosmeceuticals. Methods: A systematic review of studies published over the past two decades was conducted using the databases PubMed, Scopus, and Web of Science. The selection criteria included clinical, in silico, in vivo, and in vitro studies investigating the pharmacological and therapeutic effects of carotenoids. Results: Carotenoids demonstrate a variety of health benefits, including the prevention of age-related macular degeneration, cancer, cognitive decline, metabolic disorders, and skin aging. Their role in nutraceuticals is well supported by their ability to modulate oxidative stress and inflammatory pathways. In pharmaceuticals, carotenoids show promising results in formulations targeting neurodegenerative diseases and metabolic disorders. In cosmeceuticals, they improve skin health by protecting it against UV radiation and oxidative damage. However, bioavailability, optimal dosages, toxicity, and interactions with other bioactive compounds remain critical factors to maximize therapeutic efficacy and still require careful evaluation by scientists. Conclusions: Carotenoids are promising bioactive compounds for antiaging interventions with potential applications in a variety of fields. Further research is needed to optimize their formulas, improve bioavailability, and confirm their long-term safety and effectiveness, especially in the aging population.
Chronic pain lasting more than three months or persisting after normal healing is a significant global health issue. In a healthcare system, it is crucial to ensure proper chronic pain management. Traditional pharmacological and non-pharmacological pain management techniques may not fully meet the requirements of physicians regarding effectiveness and safety. Therefore, researchers are exploring natural analgesics. Plant-based phytoconstituents show promise in relieving chronic pain associated with various diseases. This study aims to review the latest advances in discovering natural bioactive compounds that can help alleviate chronic pain. It discusses the pathways of chronic pain and a multifactorial treatment strategy. It also organizes data on using plant- derived substances, such as cannabinoids, terpenoids, phenolics, and crude extracts. Additionally, it delves into the pharmacodynamics of cannabinoids, including their route of administration and elimination. The review presents the results of 22 clinical trials on various cannabinoids for pain relief. It is important to note that opioids and other alkaloids from plants are not covered in this article due to their primary use in controlling acute rather than chronic pain.
Introduction: Oral diseases are among the most common long-term conditions affecting the population. Medicinal plants are being used as a natural remedy for oral health issues due to their medicinal properties and lower side effects and cost compared to conventional antibacterial and anti-inflammatory agents. This study aims to review and summarize the potential uses of Murraya koenigii (L.) Spreng. (syn. of Bergera koenigii L.) in dentistry and update clinicians about its implications in dental management for maintaining oral health. Materials and Methods: The data was collected by five reviewers from multiple articles, case reports, review papers, and original studies that were published in PubMed, Web of Science, and Scopus. Results and Conclusion: The extracts of Murraya koenigii is a promising alternative to synthetic therapeutic agents in dentistry. Further research is required to explore its potential use in oral health.
Objective:
The aim: To determine the concentration of markers of the immune-inflammatory response (IL-1β, IL-10, IL-1β / IL-10, hsCRP) in oral fluid in patients with diseases of periodontal tissues in combination with general somatic pathology.
Patients and methods:
Materials and methods: The study was conducted at Danylo Halytsky Lviv National Medical University, Department of therapeutic dentistry FPGE, Lviv, Ukraine. The patients were divided into two groups: the main group - 144 patients (with periodontal tissue diseases on the background of general somatic pathology) and the control group - 30 somatically and dentally healthy persons, in whose oral fluid was determined the concentration of IL-1β, IL-10, hsCRP by the enzyme immunoassay method.
Results:
Results: As a result of our research, it was found that in people with periodontal tissue diseases, against the background of general somatic pathology, there is an activation of the immune-inflammatory response, which aggravates the course of general somatic and dental diseases in this contingent of patients.
Conclusion:
Conclusions: Therefore, in patients with periodontal tissue diseases on the background of somatic diseases, a significant increase in the level of the pro-in-flammatory cytokine IL-1β and hsCRP was determined against the background of a decrease in the anti-inflammatory cytokine IL-10 in the oral fluid compared to the values in the control group.
Background and objective:
There is no clear understanding of molecular events occurring in the periodontal microenvironment during clinical disease progression. Our aim was to explore qualitative and quantitative differences in gingival crevicular fluid (GCF) protein profiles from patients diagnosed with periodontitis between non-progressive and progressive periodontal sites.
Methods:
Five systemically healthy patients diagnosed with periodontitis were monitored weekly in their progression of the disease and GCF samples from 10 candidate sites were obtained. Two groups of five sites, matched from an equal number of teeth, were selected from the five patients: Progression (PG) and Non-Progression (NP). Global protein identification was performed with high-throughput proteomic approaches and label-free analysis determined their relative abundances. Proteins were identified by Proteome Discoverer v2.4 and searched against human SwissProt protein databases. Enrichment bioinformatic analyses were performed in STRING-DB and ShinyGO environment.
Results:
1504 and 1500 proteins were identified in NP and PG respectively. Forty-eight proteins were exclusively identified in PG, while 52 were identified in NP. Moreover, 35 proteins were more abundant in PG and 29 proteins in NP (twofold change, p < .05). The NP group was mainly represented by proteins from "response to biotic stimuli and other organisms," "processes of cell death regulation," "peptidase regulation," "protein ubiquitination," and "ribosomal activity" GO categories. The most represented GO categories of the PG group were "assembly of multiprotein complexes," "catabolic processes," "lipid metabolism," and "binding to hemoglobin and haptoglobin."
Conclusions:
There are quantitative and qualitative differences in the proteome of GCF from periodontal sites according to the status of clinical progression of periodontitis. Progressive periodontitis sites are characterized by a protein profile associated with catabolic processes, immune response, and response to cellular stress, while stable periodontitis sites show a protein profile mainly related to wound repair and healing processes, cell death regulation, and chaperone-mediated autophagy. Understanding the etiopathogenic role of these profiles in progressive periodontitis may help to develop new diagnostic and therapeutic approaches.
This study aimed to quantify serum C-reactive protein (CRP) values in periodontally healthy people and explore the relationship between serum CRP levels and chronic periodontitis, and the influence of scaling as well as root planing (SRP) on serum CRP levels. The study included 100 systemically healthy adults (n = 100; 50 males and 50 females) who were separated into two groups: Group A (control) n = 50; periodontally healthy subjects and Group B (test) n = 50; subjects with chronic periodontitis. The test group (group B) was further separated randomly into two groups: B1 (n = 25) and B2 (n = 25). The clinical parameters and serum CRP levels were measured only once in Group A and before SRP in Group B1 subjects. In Group B2 subjects the clinical parameters and serum CRP levels were measured only after two months following SRP. For group A, B1, and B2 (the readings recorded after SRP) the mean gingival index scores were 0.146, 2.437, and 1.052, respectively, while the plaque index was 0.414, 2.499, and 0.954, respectively. Probing pocket depth (PPD) and clinical attachment loss (CAL) showed statistically significant differences between three groups, with higher values in patients with periodontitis before intervention (2.196 ± 0.49; 1.490 ± 0.23), respectively. Healthy controls (Group A) had a C-reactive protein level of 0.04820 mg/dL, while group B1 (test) had 1.678 mg/dL and 0.8892 mg/dL (group B2). C-reactive protein levels were observed to be greater in the test group (groups B1 and B2), and these differences were statistically significant (p < 0.001). Chronic periodontitis enhances blood levels of systemic inflammatory markers like CRP, which has been reduced by periodontal treatment with SRP.
Periodontitis (PD) is a chronic inflammatory disease that is initiated by oral microorganisms. The pathogens induce the production of cytokines, such as interleukin (IL)-17, which enhances the inflammatory response and progression of the disease. The aim of this study was to examine the expression and localization in gingival tissue of IL-17A and IL-17B in patients with periodontitis. This study included 14 patients with periodontal disease and 14 healthy subjects without periodontal disease as a control group. There were no statistically significant differences in the expression of IL-17A mRNA between patients with periodontitis and control subjects. The expression of IL-17B mRNA was statistically significantly lower in patients with periodontitis in comparison with healthy subjects (p < 0.048). The expression of IL-17A correlated significantly with the approximal plaque index. The IL-17B expression in gingival tissue correlated with the clinical attachment level. This correlation reached borderline statistical significance (p = 0.06). In immunohistochemical analysis, we have shown the highest expression of IL-17 protein in inflamed connective tissue, epithelium, and granulation tissue from gingival biopsy specimens from patients with periodontitis. In biopsy specimens from healthy individuals, no IL-17 was found in the epithelium, while an expression of IL-17 was found in the connective tissue. The results of our study confirm the involvement of IL-17 in the pathogenesis of periodontitis. Our results suggest that an increase in IL-17 protein expression in the gingival tissue of patients with periodontitis occurs at the post-translational stage.
Gingival-derived mesenchymal stem cells (GMSCs) have strong self-renewal, multilineage differentiation, and immunomodulatory properties and are expected to be applied in anti-inflammatory and tissue regeneration. However, achieving the goal of using endogenous stem cells to treat diseases and even regenerate tissues remains a challenge. Resveratrol is a natural compound with multiple biological activities that can regulate stem cell immunomodulation when acting on them. This study found that resveratrol can reduce inflammation in human gingival tissue and upregulate the stemness of GMSCs in human gingiva. In cell experiments, it was found that resveratrol can reduce the expression of TLR4, TNFα, and NFκB and activate ERK/Wnt crosstalk, thereby alleviating inflammation, promoting the proliferation and osteogenic differentiation ability of GMSCs, and enhancing their immunomodulation. These results provide a new theoretical basis for the application of resveratrol to activate endogenous stem cells in the treatment of diseases in the future.
This narrative review celebrates Europe's contribution to the current knowledge on systemically administered antimicrobials in periodontal treatment. Periodontitis is the most frequent chronic noncommunicable human disease. It is caused by dysbiotic bacterial biofilms and is commonly treated with subgingival instrumentation. However, some sites/patients do not respond adequately, and its limitations and shortcomings have been recognized. This has led to the development of alternative or adjunctive therapies. One is the use of antimicrobials to target bacteria in subgingival biofilms in the periodontal pocket, which can be targeted directly through the pocket entrance with a locally delivered antibiotic or systemically by oral, intravenous, or intramuscular methods. Since the early 20th century, several studies on systemic antibiotics have been undertaken and published, especially between 1990 and 2010. Europe's latest contribution to this topic is the first European Federation of Periodontology, S3‐level Clinical Practice Guideline, which incorporates recommendations related to the use of adjuncts to treat stage I‐III periodontitis. Understanding the etiopathogenesis of periodontal diseases, specifically periodontitis, has influenced the use of systemic periodontal antibiotic therapy. Randomized clinical trials and systematic reviews with meta‐analyses have demonstrated the clinical advantages of adjunctive systemic antimicrobials. However, current recommendations are restrictive due to concerns about antibiotic misuse and the increase in microbial antibiotic resistance. European researchers have contributed to the use of systemic antimicrobials in the treatment of periodontitis through clinical trials and by providing rational guidelines. Nowadays, European researchers are exploring alternatives and directing clinical practice by providing evidence‐based guidelines to limit the use of systemic antimicrobials.
Natural products are well-known due to their antimicrobial properties. This study aimed to evaluate the antimicrobial effect of Desplac® product (composed of Aloe Vera, Propolis Extract, Green Tea, Cranberry, and Calendula) on the subgingival biofilm. Two different protocols were used to treat the 33-species biofilms: (A) 2×/day (12/12 h) for 1 min with Desplac® or Noplak Toothpaste (Chlorhexidine + Cetylpyridinium Chloride) or Oral B ProGengiva (stannous Fluoride) or a placebo gel; (B) a 12-h use of the Desplac® product or 0.12% chlorhexidine gel or a placebo gel. After 7 days of biofilm formation, the metabolic activity (MA) and biofilm profile were determined by 2,3,5-triphenyltetrazolium chloride and Checker-board DNA–DNA hybridization, respectively. Statistical analysis used the Kruskal-Wallis test followed by Dunn’s post-hoc. In protocol A, all treatments presented reduced MA compared to the placebo (p ≤ 0.05). The Desplac®-treated biofilm showed a similar microbial profile to other antimicrobials, although with higher bacterial total counts. In protocol B, MA of Desplac®-treated biofilms was lower than the placebo’s MA but higher than chlorhexidine-treated biofilms (p ≤ 0.05). Pathogen levels in Desplac®-treated biofilms were lower than in placebo-treated biofilms and elevated compared to the chlorhexidine-treated biofilms (p ≤ 0.05). Desplac® inhibited the biofilm development and disrupted the mature subgingival biofilm, highlighting its effect on Tannerella forsythia counts.
Periodontal diseases and dental caries are the most common infectious oral diseases impacting oral health globally. Oral cavity health is crucial for enhancing life quality since it serves as the entranceway to general health. The oral microbiome and oral infectious diseases are strongly correlated. Gram-negative anaerobic bacteria have been associated with periodontal diseases. Due to the shortcomings of several antimicrobial medications frequently applied in dentistry, the lack of resources in developing countries, the prevalence of oral inflammatory conditions, and the rise in bacterial antibiotic resistance, there is a need for reliable, efficient, and affordable alternative solutions for the prevention and treatment of periodontal diseases. Several accessible chemical agents can alter the oral microbiota, although these substances also have unfavorable symptoms such as vomiting, diarrhea, and tooth discoloration. Natural phytochemicals generated from plants that have historically been used as medicines are categorized as prospective alternatives due to the ongoing quest for substitute products. This review concentrated on phytochemicals or herbal extracts that impact periodontal diseases by decreasing the formation of dental biofilms and plaques, preventing the proliferation of oral pathogens, and inhibiting bacterial adhesion to surfaces. Investigations examining the effectiveness and safety of plant-based medicines have also been presented, including those conducted over the past decade.
The effect of systemic antibiotics on the microbial profile of extracrevicular sites after periodontal treatment is currently the subject of research. This study evaluated the microbiological effects on different oral cavity sites of scaling and root planing (SRP) combined with antimicrobial chemical control in the treatment of periodontitis. Sixty subjects were randomly assigned to receive SRP alone or combined with metronidazole (MTZ) + amoxicillin (AMX) for 14 days, with or without chlorhexidine mouth rinse (CHX) for 60 days. Microbiological samples were evaluated by checkerboard DNA–DNA hybridization until 180 days post therapy. The adjunctive use of antibiotics plus CHX significantly reduced the mean proportions of red complex species from subgingival biofilm and saliva (p < 0.05). Furthermore, the analysis of all intraoral niches showed a significantly lower mean proportion of the red complex species in the same group. In conclusion, the concomitant use of antimicrobial chemical control (systemic and local) demonstrated a beneficial effect on the composition of the oral microbiota.
Periodontitis is a common disorder affecting the bone and soft tissues of the periodontal complex. When untreated, it may lead to severe mobility or even loss of teeth. The pathogenesis of periodontitis is complex, with crucial factors being chronic inflammation in gingival and periodontal tissues and oral microbiome alterations. However, recent studies highlight the alleged role of vitamins, such as vitamin C (VitC) and vitamin D (VitD), in the development of the disease. VitC regulates numerous biochemical reactions, but foremost, it is involved in synthesizing collagen. It was reported that VitC deficiency could lead to damage to the periodontal ligaments. VitC supplementation improves postoperative outcomes in patients with periodontitis. VitD is a steroid derivative that can be produced in the skin under ultraviolet radiation and later transformed into an active form in other tissues, such as the kidneys. VitD was established to decrease the expression of proinflammatory cytokines in gingiva and regulate the proper mineral density of teeth. Moreover, the supplementation of VitD was associated with better results in the nonsurgical treatment of periodontitis. In this review, we summarize recent knowledge on the role of vitamins C and D in the pathogenesis and treatment of periodontitis.
The immune system protects the body from infectious agents such as bacteria, viruses, or fungi. Once encountered with pathogens or antigens, the innate and adaptive arms of the immune sys-tem trigger a strong immune response to eliminate them from the system and protect the body. Thus, well-balanced immunity is pivotal for maintaining human health, as an insufficient level of immune defense leads to infections and tumors. In contrast, the excessive functioning of the immune system causes the development of autoimmune diseases and allergies. Strong immuni-ty requires adequate nutrition, dietary interventions, and sufficient intake of certain vitamins (vitamin C, vitamin D, and folic acid) and minerals (magnesium, zinc, and selenium). Therefore, nutritional and micronutrient deficiencies lead to compromised immunity. Several natural in-gredients have shown potent immunomodulatory properties. The immune-enhancing proper-ties of many plants and fungi are due to containing bioactive phytoconstituents such as poly-phenols, terpenoids, β-glucans, vitamins, etc. Probiotics and prebiotics can be used as innovative tools to reduce intestinal inflammation and downregulate hypersensitivity reactions. Plant sources of melatonin, a multifunctional molecule with proven anti-inflammatory and im-munomodulatory properties, have been discovered relatively recently. The bioactive com-pounds augment the immune response by directly increasing the cytotoxic activity of natural killer cells, macrophages, and neutrophils. Many phytoconstituents prevent cell damage due to their powerful antimicrobial, antioxidant, and anti-inflammatory properties. The present review attempts to understand the molecular mechanisms underlying the immune-enhancing proper-ties of some bioactive compounds from plants, fungi, animals, microorganisms, and other natu-ral sources.
Background
Periodontitis is one of the most common chronic inflammatory diseases in the world, which affects oral health. Resveratrol is a polyphenol with therapeutic effects on the inflammation caused by periodontal pathogens. This study aimed to evaluate the impact of resveratrol supplementation on clinical parameters and inflammatory markers in patients with chronic periodontitis.
Methods
In this randomized, double-blind study, 40 chronic periodontitis patients underwent non-surgical therapy and were randomly assigned to two intervention and control groups, receiving either resveratrol supplements or a placebo for four weeks. Salivary levels of interleukin-8 (IL-8), interleukin-1β (IL-1β), and clinical parameters, including pocket depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding index (BI), were measured before and after the intervention.
Results
The results showed that in both the case and control groups, after four weeks of using resveratrol, only plaque index (PI) was significantly different compared to the control group (P = 0.0001). However, there were no significant differences in the mean pocket depth (PD), clinical attachment loss (CAL), bleeding index (BI), and salivary levels of IL-8 and IL-1β between the two groups after the intervention.
Conclusion
Resveratrol complement was helpful as an anti-inflammatory food supplement, along with other non-surgical periodontal treatments in chronic periodontitis patients.
Periodontitis is one of the most common oral polymicrobial infectious diseases induced by the complex interplay between the altered subgingival microbiota and the host’s dysregulated immune-inflammatory response, leading to the initiation of progressive and irreversible destruction of the periodontal tissues and eventually to tooth loss. The main goal of cause-related periodontal therapy is to eliminate the dysbiotic subgingival biofilm in order to arrest local inflammation and further periodontal tissue breakdown. Because, in some cases, subgingival mechanical instrumentation has limited efficiency in achieving those goals, various adjunctive therapies, mainly systemic and locally delivered antimicrobials, have been proposed to augment its effectiveness. However, most adjunctive antimicrobials carry side effects; therefore, their administration should be precociously considered. HybenX® (HY) is a commercial therapeutical agent with decontamination properties, which has been studied for its effects in treating various oral pathological conditions, including periodontitis. This review covers the current evidence regarding the treatment outcomes and limitations of conventional periodontal therapies and provides information based on the available experimental and clinical studies related to the HY mechanism of action and effects following its use associated with subgingival instrumentation and other types of dental treatments.
The break of the epithelial barrier of gingiva has been a subject of minor interest, albeit playing a key role in periodontal pathology, transitory bacteraemia, and subsequent systemic low-grade inflammation (LGI). The significance of mechanically induced bacterial translocation in gingiva (e.g., via mastication and teeth brushing) has been disregarded despite the accumulated knowledge of mechanical force effects on tight junctions (TJs) and subsequent pathology in other epithelial tissues. Transitory bacteraemia is observed as a rule in gingival inflammation, but is rarely observed in clinically healthy gingiva. This implies that TJs of inflamed gingiva deteriorate, e.g., via a surplus of lipopolysaccharide (LPS), bacterial proteases, toxins, Oncostatin M (OSM), and neutrophil proteases. The inflammation-deteriorated gingival TJs rupture when exposed to physiological mechanical forces. This rupture is characterised by bacteraemia during and briefly after mastication and teeth brushing, i.e., it appears to be a dynamic process of short duration, endowed with quick repair mechanisms. In this review, we consider the bacterial, immune, and mechanical factors responsible for the increased permeability and break of the epithelial barrier of inflamed gingiva and the subsequent translocation of both viable bacteria and bacterial LPS during physiological mechanical forces, such as mastication and teeth brushing.
Both periodontitis and Coronavirus disease 2019 (COVID-19) pose grave threats to public health and social order, endanger human life, and place a significant financial strain on the global healthcare system. Since the COVID-19 pandemic, mounting research has revealed a link between COVID-19 and periodontitis. It is critical to comprehend the immunological mechanisms of the two illnesses as well as their immunological interaction. Much evidence showed that there are many similar inflammatory pathways between periodontitis and COVID-19, such as NF-κB pathway, NLRP3/IL-1β pathway, and IL-6 signaling pathway. Common risk factors such as gender, lifestyle, and comorbidities contribute to the severity of both diseases. Revealing the internal relationship between the two diseases is conducive to the treatment of the two diseases in an emergency period. It is also critical to maintain good oral hygiene and a positive attitude during treatment. This review covers four main areas: immunological mechanisms, common risk factors, evidence of the association between the two diseases, and possible interventions and potential targets. These will provide potential ideas for drug development and clinical treatment of the two diseases.
Dental implants to replace lost teeth are a common dentistry practice nowadays. Titanium dental implants display a high success rate and improved safety profile. Nevertheless, there is an increasing peri-implantitis (PI), an inflammatory disease associated with polymicrobial infection that adversely affects the hard and soft tissues around the implant. The present review highlights the contribution of different metabolic conditions to PI. The considerations of both local and systemic metabolic conditions are crucial for planning successful dental implant procedures and during the treatment course of PI. Un- or undertreated PI can lead to permanent jaw bone suffering and dental implant losses. The common mediators of PI are inflammation and oxidative stress, which are also the key mediators of most systemic metabolic disorders. Chronic periodontitis, low-grade tissue inflammation, and increased oxidative stress raise the incidence of PI and the underlying systemic metabolic conditions, such as obesity, diabetes mellitus, or harmful lifestyle factors (cigarette smoking, etc.). Using dental biomaterials with antimicrobial effects could partly solve the problem of pathogenic microbial contamination and local inflammation. With local dentistry considering factors, including oral microbiota and implant quality control, the inclusion of the underlying systemic metabolic conditions into the pre-procedure planning and during the treatment course should improve the chances of successful outcomes.
Aging is a very complex process that is accompanied by a degenerative impairment in many of the major functions of the human body over time. This inevitable process is influenced by hereditary factors, lifestyle, and environmental influences such as xenobiotic pollution, infectious agents, UV radiation, diet-borne toxins, and so on. Many external and internal signs and symptoms are related with the aging process and senescence, including skin dryness and wrinkles, atherosclerosis, diabetes, neurodegenerative disorders, cancer, etc. Oxidative stress, a consequence of the imbalance between pro- and antioxidants, is one of the main provoking factors causing aging-related damages and concerns, due to the generation of highly reactive byproducts such as reactive oxygen and nitrogen species during the metabolism, which result in cellular damage and apoptosis. Antioxidants can prevent these processes and extend healthy longevity due to the ability to inhibit the formation of free radicals or interrupt their propagation, thereby lowering the level of oxidative stress. This review focuses on supporting the antioxidant system of the organism by balancing the diet through the consumption of the necessary amount of natural ingredients, including vitamins, minerals, polyunsaturated fatty acids (PUFA), essential amino acids, probiotics, plants’ fibers, nutritional supplements, polyphenols, some phytoextracts, and drinking water.
Polyphenols (PPs) are a large group of phytochemicals containing phenolic rings with two or more hydroxyl groups. They possess powerful antioxidant properties, multiple therapeutic effects, and possible health benefits in vivo and in vitro, as well as reported clinical studies. Considering their free-radical scavenging and anti-inflammatory properties, these substances can be used to treat different kinds of conditions associated with metabolic disorders. Many symptoms of metabolic syndrome (MtS), including obesity, dyslipidemia, atherosclerosis, elevated blood sugar, accelerating aging, liver intoxication, hypertension, as well as cancer and neurodegenerative disorders, are substantially relieved by dietary PPs. The present study explores the bioprotective properties and associated underlying mechanisms of PPs. A detailed understanding of these natural compounds will open up new opportunities for producing unique natural PP-rich dietary and medicinal plans, ultimately affirming their health benefits.
Periodontitis, being a multifactorial disorder is found to be the most common oral disease denoted by the inflammation of gingiva and resorption of tooth supporting alveolar bone. The disease being closely linked with fast life style and determined by unhygienic behavioural factors, the internal milieu of oral cavity and formation of plaque biofilm on the dental and gingival surfaces. Porphyromonas gingivalis, being the major keystone pathogen of the periodontal biofilm evokes host immune responses that causes damage of gingival tissues and resorption of bones. The biofilm associated microbial community progressively aggravates the condition resulting in chronic inflammation and finally tooth loss. The disease often maintains bidirectional relationship with different systemic, genetic, autoimmune, immunodeficiency diseases and even psychological disorders. The disease can be diagnosed and predicted by various genetic, radiographic and computer-aided design (CAD) & computer-aided engineering (CAE) and artificial neural network (ANN). The elucidation of genetic background explains the inheritance of the disease. The therapeutic approaches commonly followed include mechanical removal of dental plaque with the use of systemic antibiotics. Awareness generation amongst local people, adoption of good practice of timely tooth brushing preferably with fluoride paste or with nanoconjugate pastes will reduce the chance of periodontal plaque formation. Modern tissue engineering technology like 3D bioprinting of periodontal tissue may help in patient specific flawless regeneration of tooth structures and associated bones.
The COVID-19 outbreak seems to be the most dangerous challenge of the third millennium due to its highly contagious nature. Amongst natural molecules for COVID-19 treatment, the flavonoid molecule quercetin (QR) is currently considered one of the most promising. QR is an active agent against SARS and MERS due to its antimicrobial, antiviral, anti-inflammatory, antioxidant, and some other beneficial effects. QR may hold therapeutic potential against SARS-CoV-2 due to its inhibitory effects on several stages of the viral life cycle. In fact, QR inhibits viral entry, absorption, and penetration in the SARS-CoV virus, which might be at least partly explained by the ability of QR and its derivatives to inhibit 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro). QR is a potent immunomodulatory molecule due to its direct modulatory effects on several immune cells, cytokines, and other immune molecules. QR-based nanopreparations possess enhanced bioavailability and solubility in water. In this review, we discuss the prospects for the application of QR as a preventive and treatment agent for COVID-19. Given the multifactorial beneficial action of QR, it can be considered a very valid drug as a preventative, mitigating, and therapeutic agent of COVID-19 infection, especially in synergism with zinc, vitamins C, D, and E, and other polyphenols.
Periodontitis is an oral inflammatory process involving the periodontium, which is mainly caused by the invasion of periodontopathogenic microorganisms that results in gingival connective tissue and alveolar bone destruction. Metabolic products of the oral pathogens and the associated host immune and inflammatory responses triggered are responsible for the local tissue destruction. Numerous studies in the past decades have demonstrated that natural polyphenols are capable of modulating the host inflammatory responses by targeting multiple inflammatory components. The proposed mechanism by which polyphenolic compounds exert their great potential is by regulating the immune cell, proinflammatory cytokines synthesis and gene expression. However, due to its low absorption and bioavailability, the beneficial effects of these substances are very limited and it hampers their use as a therapeutic agent. To address these limitations, targeted delivery systems by nanoencapsulation techniques have been explored in recent years. Nanoencapsulation of polyphenolic compounds with different carriers is an efficient and promising approach to boost their bioavailability, increase the efficiency and reduce the degradability of natural polyphenols. In this review, we focus on the effects of different polyphenolic substances in periodontal inflammation and to explore the pharmaceutical significance of polyphenol-loaded nanoparticles in controlling periodontitis, which may be useful for further enhancement of their efficacy as therapeutic agents for periodontal disease.
Over the last few decades, studies on the oral microbiome have increased awareness that the balance between the host and the microbial species that coexist in it is essential for oral health at all stages of life. However, this balance is extremely difficult to maintain, and many factors can disrupt it: general eating habits, sugar consumption, tobacco smoking, oral hygiene, and use of antibiotics and other antimicrobials. It is now known that alterations in the oral microbiota are responsible for developing and promoting many oral diseases, including periodontal disease. In this context, diet is an area for further investigation as it has been observed that the intake of particular foods, such as farmed animal meat, dairy products, refined vegetable oils, and processed cereals, affects the composition of the microbiota, leading to an increased representation of acid-producing and acid-tolerant organisms and periodontal pathogens. However, little is known about the influence of diet on the oral microbiome and the creation of a suitable microenvironment for the development of periodontal disease. The aim of the present study is to evaluate current knowledge on the role of diet in the oral dysbiosis underlying periodontal disease.
Periodontitis is an infectious oral disease, which leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, it is urgent to explore new therapeutic strategies for periodontitis. Natural products show anti-microbial, anti-inflammatory, anti-oxidant and bone protective effects to periodontitis and most of these natural products are safe and cost-effective. Among these, the plant-derived exosome-like nanoparticles (PELNs), a type of natural nanocarriers repleted with lipids, proteins, RNAs, and other active molecules, show the ability to enter mammalian cells and regulate cellular activities. Reports from the literature indicate the great potential of PELNs in the regulation of immune functions, inflammation, microbiome, and tissue regeneration. Moreover, PELNs can also be used as drug carriers to enhance drug stability and cellular uptake in vivo. Since regulation of immune function, inflammation, microbiome, and tissue regeneration are the key phenomena usually targeted during periodontitis treatment, the PELNs hold the promising potential for periodontitis treatment. This review summarizes the recent advances in PELNs-related research that are related to the treatment of periodontitis and regeneration of periodontitis-destructed tissues and the underlying mechanisms. We also discuss the existing challenges and prospects of the application of PELNs-based therapeutic approaches for periodontitis treatment.
For many years, the use of probiotics in periodontitis treatment was reflected in their abilities to control the immune response of the host to the presence of pathogenic microorganisms and to upset periodontopathogens. Accordingly, the aim of the present study was to assess the use of probiotics as adjuvant therapy on clinical periodontal parameters throughout a systematic review and meta-analysis. The literature was screened, up to 4 June 2021, by two independent reviewers (L.H. and R.B.) in four electronic databases: PubMed (MedLine), ISI Web of Science, Scielo, and Scopus. Only clinical trials that report the effect of the use of probiotics as adjuvants in the treatment of periodontal disease were included. Comparisons were carried out using Review Manager Software version 5.3.5 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). A total of 21 studies were considered for the meta-analysis. For the index plaque, the use of probiotics did not improve this clinical parameter (p = 0.16). On the other hand, for the periodontal pocket depth, the clinical attachment loss, the bleeding on probing, and the use of probiotics as adjuvant therapy resulted in an improvement of these parameters, since the control group achieved statistically higher values of this parameter (p < 0.001; p < 0.001; and p = 0.005, respectively). This study suggests that the use of probiotics led to an improvement in periodontal pocket depth, clinical attachment loss, and bleeding on probing parameters. On the other hand, this protocol seems to not be beneficial for the index plaque parameter.
Periodontitis is a microbially driven host-mediated disease that leads to loss of periodontal attachment and bone. It is associated with elevation of systemic inflammatory markers and with the presence of systemic co-morbidities. Furthermore, periodontal treatment leads to a 24–48 h-long acute local and systemic inflammatory response. This systemic response might increase the burden of patients with compromised medical history and/or uncontrolled systemic diseases. The correlation between periodontitis and systemic diseases, the impact of periodontitis on the quality of life and public health, the effects of periodontal treatment on systemic health and disease, and the available methods to manage systemic inflammation after periodontal therapy are discussed. The main focus then shifts to a description of the existing evidence regarding the impact of periodontitis and periodontal treatment on systemic health and to the identification of approaches aiming to reduce the effect of periodontitis on systemic inflammation.
The management of periodontitis remains a vital clinical challenge due to the interplay between the microorganisms of the dental biofilm and the host inflammatory response leading to a degenerative process in the surrounding tissues. Quercetin (QUE), a natural flavonol found in many foods, including apples, onions and tea, has exhibited prolonged and strong antibiofilm and anti-inflammatory effects both in vitro and in vivo. However, its clinical application is limited by its poor stability and water solubility, as well as its low bioavailability. Thus, in the present study, electrospun polylactic acid (PLA) nanofibers loaded with different amounts (5–10% w/w) of QUE were produced to rapidly respond to the acidic microenvironment typical of periodontal pockets during periodontal disease. This strategy demonstrated that PLA-QUE membranes can act as a drug reservoir releasing high QUE concentrations in the presence of oral bacterial infection (pH < 5.5), and thus limiting Pseudomonas aeruginosa PAO1 and Streptococcus mutans biofilm maturation. In addition, released QUE exerts antioxidant and anti-inflammatory effects on P. gingivalis Lipopolysaccharide (LPS)-stimulated human gingival fibroblast (HGFs). The reported results confirmed that PLA-QUE membranes could inhibit subgingival biofilm maturation while reducing interleukin release, thereby limiting host inflammatory response. Overall, this study provided an effective pH-sensitive drug delivery system as a promising strategy for treating periodontitis.
Periodontal diseases are one of the most common chronic inflammatory diseases of the oral cavity, which are initiated and sustained by pathogenic plaque biofilms. Central to modern periodontology is the idea that dysbiosis of periodontal microecology and disorder of host inflammatory response gives rise to degradation of periodontal tissues together, which eventually leads to tooth loss, seriously affecting the life quality of patients. Probiotics were originally used to treat intestinal diseases, while in recent years, extensive studies have been exploring the utilization of probiotics in oral disease treatment and oral healthcare. Probiotic bacteria derived from the genera Lactobacillus, Bifidobacterium, Streptococcus, and Weissella are found to play an effective role in the prevention and treatment of periodontal diseases via regulating periodontal microbiota or host immune responses. Here, we review the research status of periodontal health-promoting probiotic species and their regulatory effects. The current issues on the effectiveness and safety of probiotics in the management of periodontal diseases are also discussed at last. Taken together, the use of probiotics is a promising approach to prevent and treat periodontal diseases. Nevertheless, their practical use for periodontal health needs further research and exploration.
This review aims to analyze propolis as a potential raw material for the development and manufacture of new health-promoting products. Many scientific publications were retrieved from the Scopus, PubMed, and Google Scholar databases via searching the word "propolis". The different extraction procedures, key biologically active compounds, biological properties, and therapeutic potential of propolis were analyzed. It was concluded that propolis possesses a variety of biological properties because of a very complex chemical composition that mainly depends on the plant species visited by bees and species of bees. Numerous studies found versatile pharmacological activities of propolis: antimicrobial, antifungal, antiviral, antioxidant, anticancer, anti-inflammatory, immunomodulatory, etc. In this review, the composition and biological activities of propolis are presented from a point of view of the origin and standardization of propolis for the purpose of the development of new pharmaceutical products on its base. It was revealed that some types of propolis, especially European propolis, contain flavonoids and phenolic acids, which could be markers for the standardization and quality evaluation of propolis and its preparations. One more focus of this paper was the overview of microorganisms’ sensitivity to propolis for further development of antimicrobial and antioxidant products for the treatment of various infectious diseases with an emphasis on the illnesses of the oral cavity. It was established that the antimicrobial activity of different types of propolis is quite significant, especially to Gram-negative bacteria and lipophilic viruses. The present study could be also of interest to the pharmaceutical industry as a review for the appropriate design of standardized propolis preparations such as mouthwashes, toothpastes, oral drops, sprays, creams, ointments, suppositories, tablets, and capsules, etc. Moreover, propolis could be regarded as a source for the isolation of biologically active substances. Furthermore, this review can facilitate partially overcoming the problem of the standardization of propolis preparations, which is a principal obstacle to the broader use of propolis in the pharmaceutical industry. Finally, this study could be of interest in the area of the food industry for the development of nutritionally well-balanced products. The results of this review indicate that propolis deserves to be better studied for its promising therapeutic effects from the point of view of the connection of its chemical composition with the locality of its collection, vegetation, appropriate extraction methods, and standardization.
Objective:
The aim: Evaluation of changes in proinflammatory and anti-inflammatory units of the cytokine profile in the mechanisms of development of experimental bacterial-immune periodontitis and elucidation of the effect of flavonol quercetin on its parameters.
Patients and methods:
Materials and methods: Experimental periodontitis was caused by introducing into the tissues of the periodontal complex a mixture of microorganisms diluted with egg protein. In order to enhance the immune response, a complete Freund's adjuvant was injected into the rat's paw at the same time. For correction, intramuscular injections of water-soluble quercetin at a dose of 100 mg / kg body weight were performed for 7 days (7th to 14th day).
Results:
Results: The use of flavonol quercetin led to a decrease in the serum content of experimental animals with pro-inflammatory cytokines. With regard to anti-inflammatory cytokines, their content in the blood of animals during the development of this simulated inflammatory process changed in the opposite direction. Quercetin effectively eliminated the imbalance of the immune system and increased the level of IL-10 and IL-4 in the serum. After injections of quercetin, the relation of pro- and anti-inflammatory cytokines in the serum of animals on 14th day of the study was reduced compared to their content in rats that did not receive correction.
Conclusion:
Conclusions: The formation and course of experimental bacterial-immune periodontitis is accompanied by a complex of pathological changes in immunocytokinogenesis, which is manifested by a progressive increase in serum concentrations of proinflammatory cytokines and a decrease in anti-inflammatory cytokines. Flavonol quercetin reduces the concentration of pro-inflammatory and increases the content of anti-inflammatory cytokines.
Periodontitis and chronic kidney disease are both chronic inflammatory diseases and share some common risk factors. This 3-month pilot study aimed to clarify whether non-surgical periodontal therapy is beneficial in clinical, biochemical, and microbiological conditions in patients with periodontitis and kidney failure. Kidney failure patients with moderate to severe periodontitis were recruited from two hospitals. Treatment group received non-surgical periodontal therapy, and control group received oral hygiene instruction only. Outcome assessments were conducted 1 and 3 months after treatment. Non-parametric tests were used to analyze the patient-level data. Periodontal site-level assessments were analyzed by Student t-test and paired t-test. Statistical significance was set at p-value < 0.05. A total of 11 subjects completed the study. There was no significant difference between groups in all-cause mortality, cardiovascular events, infection events, systemic parameters, and serum biomarkers. Comparing to control group, clinical periodontal parameters, gingival crevicular fluid interleukin-1β (IL-1β) level and periodontal pathogens showed significant improvement in the treatment group. Non-surgical periodontal treatment did not change systemic outcomes in kidney failure patients, but changed the local micro-environment.
Periodontal diseases are one of the most significant challenges in dental health. It is estimated that only a few percent of the worldwide population have entirely healthy teeth, and according to WHO, oral diseases may affect up to 3.5 billion people worldwide. One of the most serious oral diseases is periodontitis, an inflammatory disease affecting periodontal tissues, caused by pathogenic bacteria and environmental factors such as the ageing population, abuse of tobacco products, and lack of adequate oral hygiene due low public awareness. Plant materials are widely and successfully used in the management of many conditions, including periodontitis. Plant materials for periodontitis exhibit antibacterial, anti-inflammatory, antioxidant activities and affect the periodontium structure. Numerous studies demonstrate the advantages of phytotherapy for periodontitis relief and indicate the usefulness of Baikal skullcap root, Pomegranate fruit peel and root cortex, Tea leaves, Chamomile flowers, Magnolia bark, Blackberry leaves and fruits, Cranberry fruits and Lippia sidoides essential oil. This review aims to analyze the use and applicability of selected plant materials in periodontitis management since it is of paramount importance to evaluate the evidence of the traditionally used plant materials in light of continuously growing interest in phytotherapy and its adjuvant role in the treatment of periodontitis.
Periodontal disease is classically characterized by progressive destruction of the soft and hard tissues of the periodontal complex, mediated by an interplay between dysbiotic microbial communities and aberrant immune responses within gingival and periodontal tissues. Putative periodontal pathogens are enriched as the resident oral microbiota becomes dysbiotic and inflammatory responses evoke tissue destruction, thus inducing an unremitting positive feedback loop of proteolysis, inflammation, and enrichment for periodontal pathogens. Keystone microbial pathogens and sustained gingival inflammation are critical to periodontal disease progression. However, recent studies have revealed the importance of previously unidentified microbes involved in disease progression, including various viruses, phages and bacterial species. Moreover, newly identified immunological and genetic mechanisms, as well as environmental host factors, including diet and lifestyle, have been discerned in recent years as further contributory factors in periodontitis. These factors have collectively expanded the established narrative of periodontal disease progression. In line with this, new ideologies related to maintaining periodontal health and treating existing disease have been explored, such as the application of oral probiotics, to limit and attenuate disease progression. The role of systemic host pathologies, such as autoimmune disorders and diabetes, in periodontal disease pathogenesis has been well noted. Recent studies have additionally identified the reciprocated importance of periodontal disease in potentiating systemic disease states at distal sites, such as in Alzheimer’s disease, inflammatory bowel diseases, and oral cancer, further highlighting the importance of the oral cavity in systemic health. Here we review long-standing knowledge of periodontal disease progression while integrating novel research concepts that have broadened our understanding of periodontal health and disease. Further, we delve into innovative hypotheses that may evolve to address significant gaps in the foundational knowledge of periodontal disease.
Background: Discoloration of teeth occurs for various reasons. Common ingredients like substances from tea and coffee, as well as antibiotics like tetracycline, or food dyes, can percolate into the teeth, and, as such, these stains may persist in the porous structure of the enamel. Smoking is also contributory to dental discoloration, with toxins of tobacco smoke accumulating in a similar way. With aging, teeth tend to be discolored with accumulation of various stains in addition to the enamel gradually eroding to expose the yellow dentin.
Highlight: This review focused on the effect of several natural ingredients with teeth-whitening properties and their daily clinical application. Metabolic dental bleaching mechanisms, as well as tooth discoloration and decay, were also reviewed. The current scientific literature (mostly from 2000 to 2020) was consolidated from manuscripts retrieved from Scopus, PubMed, ResearchGate, and Google Scholar.
Conclusion: Natural teeth whitening effectively lightens the natural color of teeth without eroding dental surfaces. On the other hand, commercially available whiteners containing hydrogen peroxide and carbamide peroxide, in high concentrations, can lead to deproteinization and demineralization of teeth through oxidation processes. If used extensively, these compounds may cause a number of adverse effects. Alternative natural teeth-whiteners include ingredients like lemons, strawberries, oranges, papaya, and other fruits. Such natural ingredients offer a milder and safer way of whitening teeth than whiteners containing hydrogen peroxide or carbamide peroxide.
Failure to attenuate inflammation coupled with consequent microbiota changes drives the development of bone-destructive periodontitis. Quercetin, a plant-derived polyphenolic flavonoid, has been linked with health benefits in both humans and animals. Using a systematic approach, we investigated the effect of orally delivered Quercetin on host inflammatory response, oral microbial composition and periodontal disease phenotype. In vivo, quercetin supplementation diminished gingival cytokine expression, inflammatory cell infiltrate and alveolar bone loss. Microbiome analyses revealed a healthier oral microbial composition in Quercetin-treated versus vehicle-treated group characterized by reduction in the number of pathogenic species including Enterococcus, Neisseria and Pseudomonas and increase in the number of non-pathogenic Streptococcus sp. and bacterial diversity. In vitro, Quercetin diminished inflammatory cytokine production through modulating NF-κB:A20 axis in human macrophages following challenge with oral bacteria and TLR agonists. Collectively, our findings reveal that Quercetin supplement instigates a balanced periodontal tissue homeostasis through limiting inflammation and fostering an oral cavity microenvironment conducive of symbiotic microbiota associated with health. This proof of concept study provides key evidence for translational studies to improve overall health.
Periodontitis is one of the most common dental diseases. Compared with healthy periodontal tissues, the immune microenvironment plays the key role in periodontitis by allowing the invasion of pathogens. It is possible that modulating the immune microenvironment can supplement traditional treatments and may even promote periodontal regeneration by using stem cells, bacteria, etc. New anti-inflammatory therapies can enhance the generation of a viable local immune microenvironment and promote cell homing and tissue formation, thereby achieving higher levels of immune regulation and tissue repair. We screened recent studies to summarize the advances of the immunomodulatory treatments for periodontitis in the aspects of drug therapy, microbial therapy, stem cell therapy, gene therapy and other therapies. In addition, we included the changes of immune cells and cytokines in the immune microenvironment of periodontitis in the section of drug therapy so as to make it clearer how the treatments took effects accordingly. In the future, more research needs to be done to improve immunotherapy methods and understand the risks and long-term efficacy of these methods in periodontitis.
Introduction:
Systemic antibiotics present one of the alternative adjunctive therapies in nonsurgical periodontal treatment (NSPT). Different protocols have been proposed, but their indication and effectiveness are still controversial. The aim of this study is to assess the effectiveness of the addition of antibiotics after nonsurgical debridement during initial therapy and compare different antimicrobial prescription protocols.
Materials and methods:
An electronic search was performed through MEDLINE and EBSCOhost databases using the appropriate MeSH words. The target studies have to be published during the last five years. Data from the selected studies were extracted and analyzed. Study selection was done based on inclusion and exclusion criteria.
Results:
Seven randomized clinical trials were included in our review. Their data were extracted using a grid established for this purpose. Collectively, different protocols have been proposed and almost all of them yield superior clinical and microbiological results compared to the placebo group.
Conclusion:
The overall findings of this review show a positive effect of the use of antibiotics as an adjunctive to NSPT, regardless of the antimicrobial agents used in our included studies. Sites with PD > 6 mm may benefit most from the adjunctive use of antibiotics in NSPT. This trial is registered with Clinicaltrials.gov identifiers: NCT02829983 (Bechara Andere et al., 2016); NCT02839421 (Ardila et al., 2020); NCT02735395 (Borges et al., 2017); NCT02359721 (Suryaprasanna et al., 2018); and NCT01318928 (Hans, 2015).
The aim of this study was to determine the effect of propolis on nonsurgical
periodontal therapy in patients with chronic periodontitis (CP) as it appears in
the recent literature. Propolis is a natural and biocompatible resinous substance that
has shown, by means of several scientific studies, to possess medicinal properties
such as antimicrobial, healing, anesthetic, anti-inflammatory, and analgesic, among
others. There are several studies that have reported the use of propolis as a nonsurgical
treatment of CP, its comparison with other antimicrobials, and the improvement
of clinical and microbiological parameters with scaling and root planing (SRP). A
bibliographic search was conducted in the PubMed, Google Scholar, Web of Science,
and Science Direct databases up to 2021. The results showed that there are very few
reports focused on clinical studies; however, according to the analyzed data, propolis
could be a good adjuvant for the treatment of patients with chronic periodontitis
compared to the conventional treatment (SRP).
The aim of this review was to update the evidence of new approaches to non-surgical therapy (NSPT) in the treatment of periodontitis. Preclinical and clinical studies addressing the benefits of adjunctive antimicrobial photodynamic therapy, probiotics, prebiotics/synbiotics, statins, pro-resolving mediators, omega-6 and -3, ozone, and epigenetic therapy were scrutinized and discussed. Currently, the outcomes of these nine new approaches, when compared with subgingival debridement alone, did not demonstrate a significant added clinical benefit. However, some of these new alternative interventions may have the potential to improve the outcomes of NSPT alone. Future evidence based on randomized controlled clinical trials would help clinicians and patients in the selection of different adjunctive therapies.
Due to its vast therapeutic potential, the plant-derived polyphenol curcumin is utilized in an ever-growing number of health-related applications. Here, we report the extraction methodologies, therapeutic properties, advantages and disadvantages linked to curcumin employment, and the new strategies addressed to improve its effectiveness by employing advanced nanocarriers. The emerging nanotechnology applications used to enhance CUR bioavailability and its targeted delivery in specific pathological conditions are collected and discussed. In particular, new aspects concerning the main strategic nanocarriers employed for treating inflammation and oxidative stress-related diseases are reported and discussed, with specific emphasis on those topically employed in conditions such as wounds, arthritis, or psoriasis and others used in pathologies such as bowel (colitis), neurodegenerative (Alzheimer’s or dementia), cardiovascular (atherosclerosis), and lung (asthma and chronic obstructive pulmonary disease) diseases. A brief overview of the relevant clinical trials is also included. We believe the review can provide the readers with an overview of the nanostrategies currently employed to improve CUR therapeutic applications in the highlighted pathological conditions.
Periodontal disease encompasses gingivitis and periodontitis and is one of the most common chronic infections in the adult population. This study aimed to evaluate the influence of Spanish propolis extract (EEP) on the effect of the clinical and microbiological parameters as an adjuvant to scaling and root planning in patients undergoing supportive periodontal therapy (SPT). Forty chronic periodontitis patients were randomly assigned into two groups for the treatment. In the control group (n = 20), the sites were treated by scaling and root planing followed by gingival irrigation with physiological saline and in the test group (n = 20), the sites were treated by scaling and root planing followed by subgingival placement of EEP. At baseline (BL), bleeding on probing positive (BOP+) sites with probing pocket (PPD) ≥ 4 mm were defined as study sites. Plaque index, PPD, BOP, clinical attachment level (CAL), and subgingival plaque were evaluated at BL and 1 month later. The results showed a significant clinical improvement (p < 0.05) in the PPD, CAL and BOP+ comparing them with BL and one month after the periodontal treatment and a significant reduction (p < 0.05) for Tannerella forsythensis, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola in both groups. In addition, the improvement of clinical parameters was observed with subgingival use of EEP and also statistically significant differences between groups were observed (p < 0.05) such as reductions of BOP+ % and reduced counts of T. forsythensis and P. gingivalis, considered as the “key pathogens” for the periodontal diseases. Our results suggest prophylactic and therapeutic potential for EEP against periodontal diseases, improving clinical parameters, reducing gingival bleeding and decreasing bacterial counts of T. forsythensis and P. gingivalis. The subgingival use of EEP represents a promising modality as an adjuvant in periodontal therapy to avoid microbial resistance and other adverse effects.
Purpose
Emerging evidence has indicated that oxidative stress (OS) contributes to periodontitis. Periodontal ligament cells (PDLCs) are important for the regeneration of periodontal tissue. Quercetin, which is extracted from fruits and vegetables, has strong antioxidant capabilities. However, whether and how quercetin affects oxidative damage in PDLCs during periodontitis remains unknown. The aim of this study was to assess the effects of quercetin on oxidative damage in PDLCs and alveolar bone loss in periodontitis and underlying mechanisms.
Materials and Methods
The tissue block culture method was used to extract human PDLCs (hPDLCs). First, a cell counting kit 8 (CCK-8) assay was used to identify the optimal concentrations of hydrogen peroxide (H2O2) and quercetin. Subsequently, a 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe, RT-qPCR, Western blotting and other methods were used to explore the effects of quercetin on OS in hPDLCs and the underlying mechanism. Finally, quercetin was administered to mice with periodontitis through gavage, and the effect of quercetin on the level of OS and alveolar bone resorption in these mice was observed by immunofluorescence, microcomputed tomography (micro-CT), hematoxylin and eosin staining (H&E) staining and so on.
Results
Quercetin at 5 μM strongly activated NF-E2–related factor 2 (NRF2) signaling, alleviated oxidative damage and enhanced the antioxidant capacity of hPDLCs. In addition, quercetin reduced cellular senescence and protected the osteogenic ability of hPDLCs. Finally, quercetin activated NRF2 signaling in the periodontal ligaments, reduced the OS level of mice with periodontitis, and slowed the absorption of alveolar bone in vivo.
Conclusion
Quercetin can increase the antioxidant capacity of PDLCs and reduce OS damage by activating the NRF2 signaling pathway, which alleviates alveolar bone loss in periodontitis.
Introduction:
Propolis is a natural composite balsam. In the past decade, propolis has been extensively investigated as an adjuvant for the treatment of periodontitis. This study aimed to investigate antimicrobial activities of propolis solutions and plant essential oils against some oral cariogenic (Streptococcus mutans, Streptococcus mitis, Streptococcus sanguis, Lactobacillus acidophilus) and periodontopathic bacteria (Actinomyces odontolyticus, Eikenella corrodens, Fusobacterium nucleatum).
Methodology:
Determination of the minimum inhibitory concentration (MIC): The antimicrobial activity of propolis and essential oils was investigated by the agar dilution method. Serial dilutions of essential oils were prepared in plates, and the assay plates were estimated to contain 100, 50, 25 and 12.5 µg/mL of active essential oils. Dilutions for propolis were 50, 25, 12.5 and 6.3 µg/mL of active propolis solutions.
Results:
Propolis solutions dissolved in benzene, diethyl ether and methyl chloride, demonstrated equal effectiveness against all investigated oral bacteria (MIC=12.5 µg/mL). Propolis solution dissolved in acetone displayed MIC of 6.3 µg/mL only for Lactobacillus acidophilus. At the MIC of 12.5 µg/mL, essential oils of Salvia officinalis and Satureja kitaibelii were effective against Streptococcus mutans and Porphyromonas gingivalis, respectively. For the latter, the MIC value of Salvia officinalis was twice higher.
Conclusions:
The results indicate that propolis and plant essential oils appear to be a promising source of antimicrobial agents that may prevent dental caries and other oral infectious diseases.
Natural products, including propolis, are now frequently used to treat periodontal disease, but there are a few clinical studies in this area. The aim of this randomized clinical trial was to evaluate the effect of subgingival irrigation of periodontal pockets with a hydroalcoholic solution of propolis extract 20% (w/v) as an adjunct to periodontal therapy. Sixteen individuals were divided into a test group (TG), comprised 65 teeth (scaling and root planing + irrigation with propolis solution), and a control group (CG), comprised 62 teeth (scaling and root planing + irrigation with saline solution). Clinical data such as probing depth, plaque index, gingival index and oral hygiene index were collected at baseline (T0) and after 45 (T1), 75 (T2) and 90 (T3) days. Both groups showed significant differences among the evaluated periods. The TG presented more reduction (p < 0.05) of probing depth than CG at T1 and T3. Within the limits of this short-term study, these data suggest that irrigation with a hydroalcoholic solution of propolis extract 20% (w/v) as an adjunct in periodontal treatment was more effective than the mechanical treatment with saline solution in terms of reducing probing depth for up to 90 days from the beginning of treatment.
Objective:
This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy.
Methods:
The potential therapeutic targets of curcumin and differentially expressed genes in periodontitis were identified. Subsequently, we extracted the molecules in common and analyzed them. A metabolic pathway enrichment and gene ontology analysis were performed and the protein-protein interaction network was inferred. These analyses allowed the identification of key proteins. Finally, a molecular docking of the main key proteins was performed with curcumin.
Results:
Our results showed that 55 genes are differentially expressed in periodontitis and are potential targets of curcumin. In addition, we observed that these genes participate in cell motility and immune response and are related to chemokine receptors (CXCRs) and enzymatic activity, such as arachidonate 5-lipoxygenase (ALOX5). We identified six key proteins, IL1B, CXCL8, CD44, MMP2, EGFR, and ITGAM; molecular docking revealed that these six proteins spontaneously bind to curcumin.
Conclusion:
The results of this study helps us understand the molecular mechanism of curcumin in periodontitis. We propose that curcumin affects proinflammatory cytokines, ALOX5, and cell migration through chemokine receptors and acts on the cell membrane. Additionally, we identified six key proteins that are essential in this mechanism, all of which spontaneously bind to curcumin.
https://authors.elsevier.com/a/1hcFT4okfY3BTo
Background and objectives:
Cigarette smoking has been reported as an independent risk factor for periodontitis. Tobacco toxins affect periodontal tissue not only locally but also systemically, leading to the deterioration and recurrence of periodontitis. However, the mechanism of cigarette smoke-related periodontitis (CSRP) is unclear and thus lacks targeted treatment strategies. Quercetin, a plant-derived polyphenolic flavonoid, has been reported to have therapeutic effects on periodontitis due to its documented antioxidant activity. This study aimed to evaluate the effects of quercetin on CSRP and elucidated the underlying mechanism.
Methods:
The cigarette smoke-related ligature-induced periodontitis mouse model was established by intraperitoneal injection of cigarette smoke extract (CSE) and silk ligation of bilateral maxillary second molars. Quercetin was adopted by gavage as a therapeutic strategy. Micro-computed tomography was used to evaluate the alveolar bone resorption. Immunohistochemistry detected the oxidative stress and autophagy markers in vivo. Cell viability was determined by Cell Counting Kit-8, and oxidative stress levels were tested by 2,7-dichlorodihydrofluorescein diacetate probe and lipid peroxidation malondialdehyde assay kit. Alkaline phosphatase and alizarin red staining were used to determine osteogenic differentiation. Network pharmacology analysis, molecular docking, and western blot were utilized to elucidate the underlying molecular mechanism.
Results:
Alveolar bone resorption was exacerbated and oxidative stress products were accumulated during CSE exposure in vivo. Oxidative stress damage induced by CSE caused inhibition of osteogenic differentiation in vitro. Quercetin effectively protected the osteogenic differentiation of human periodontal ligament cells (hPDLCs) and periodontal tissue by upregulating the expression of Beclin-1 thus to promote autophagy and reduce oxidative stress damage.
Conclusion:
Our results established a role of oxidative stress damage and autophagy dysfunction in the mechanism of CSE-induced destruction of periodontal tissue and hPDLCs, and provided a potential application value of quercetin to ameliorate CSRP.
Objectives:
To investigate the association between periodontal disease and the development of inflammatory arthritides (IA) in the general population.
Methods:
In total, 489 125 participants from the UK Biobank without a previous history of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) were enrolled. The primary outcome was the incidence of IA, which was a composite of RA, AS, and PsA according to the presence of periodontal disease based on self-reported oral health indicators. Multivariate Cox proportional hazard regression analyses using four different models were performed to assess the association between periodontal disease and IA development.
Results:
In all, 86 905 and 402 220 individuals were categorized as with and without periodontal disease, respectively. Cox hazard analysis indicated that the presence of periodontal disease was an independent predictor of the occurrence of composite outcomes of IA, which was also consistent for RA and AS. Significant associations were found to be consistent in the four Cox models and were replicated even when different criteria were used to define periodontal disease. Subgroup analyses indicated that periodontal disease was associated with an increased RA risk in those aged <60 years, and this risk was persistent for both male and female patients and for patients with seropositive/seronegative RA.
Conclusion:
Self-reported periodontal disease is associated with IA incidence in participants included in the UK Biobank, particularly for RA and AS. Higher clinical attention and optimal dental care in patients with signs of periodontal disease may be recommended for early disease detection and for reducing this risk.
Aim:
This study evaluates the long-term risk of immune-mediated systemic conditions in individuals with periodontitis compared to those without.
Data sources:
A structured online search was conducted in Medline, Cochrane library, and EMBASE using MeSH terms. All the databases were explored from initiation to June 2022. Reference lists of the eligible studies were hand searched as well.
Study selection:
Peer-reviewed longitudinal retrospective/prospective cohorts and randomized controlled trials comparing incident metabolic/autoimmune/inflammatory diseases in periodontitis to healthy individuals were deemed eligible. Only studies with a minimum follow-up of one year were included.
Data extraction and synthesis:
The authors checked demographics, data source, exclusion/inclusion criteria, total follow-up duration, disease outcome, and limitations to determine the eligible studies. After assessing the risk of bias for the included studies using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool, the authors used the following measures to quantify the disease outcome: relative risk (RR), odds ratio (OR), and hazard ratio (HR). Systemic conditions were categorized as immune-mediated via disrupted metabolic networks (diabetes, kidney disease, liver disease, metabolic syndrome) or chronic inflammation (inflammatory bowel disease, osteoporosis, RA, psoriasis, Sjogren's syndrome), hence recognized as metabolic or autoimmune/inflammatory diseases, respectively. A random effect meta-analysis was used to synthesize the risk of developing each disease. The authors performed subgroup analysis for periodontitis diagnosis type (self-report/clinically diagnosed) and severity. They also conducted a sensitivity analysis to assess the effect of removing studies that did not adjust for smoking status.
Results:
From 3354 studies, 166 full texts were screened. Finally, 30 studies were deemed eligible for the systematic review, of which 27 made it to the meta-analysis. The risks of diabetes, rheumatoid arthritis (RA) and osteoporosis were increased in individuals with periodontitis compared to those without periodontitis (diabetes-relative risk [RR]: 1.22, 95% CI: 1.13-1.33; RA-RR: 1.27, 95% CI: 1.07-1.52; osteoporosis-RR: 1.40, 95% CI: 1.12-1.75). The risk of diabetes showed a gradient increase by periodontitis severity (moderate-RR = 1.20, 95% CI = 1.11-1.31; severe-RR = 1.34, 95% CI = 1.10-1.63).
Conclusions:
People with moderate-to-severe periodontitis have the highest risk of developing diabetes. In contrast, the effect of periodontal severity on the risk of other immune-mediated systemic conditions requires further investigation. More homologous evidence is needed to assess the periodontitis-multimorbidity association further.
Periodontitis is defined as a chronic inflammatory disease in which the continuous activation of oxidative stress surpasses the reactive oxygen species (ROS) scavenging capacity of the endogenous antioxidative defense system. Studies have demonstrated that ROS-scavenging biomaterials should be promising candidates for periodontitis therapy. To benefit the understanding and design of scavenging biomaterials for periodontitis, this review details the relationship between ROS and periodontitis, including direct and indirect damage, the application of ROS-scavenging biomaterials in periodontitis, including organic and inorganic ROS-scavenging biomaterials, and the various dosage forms of fabricated materials currently used for periodontal therapy. Finally, the current situation and further prospects of ROS-scavenging biomaterials in periodontal applications are summarized. Expecting that improved ROS-scavenging biomaterials could be better designed and developed for periodontal and even clinical application.
Objective:
To explore the prevalence of periodontal disease in middle-aged and elderly patients and analyze its influencing factors.
Methods:
A total of 521 patients admitted to the Department of Stomatology of Fuyang District Chinese Medicine Hospital of Hangzhou from January 2019 to January 2022 were retrospectively collected as study subjects, including 176 patients aged 35-44 years old, 175 patients aged 45-64 years old, and 170 patients aged 65-74 years old. Community Periodontal Index (CPI) probe was used to detect gingival bleeding, periodontal pockets and attachment loss, and the prevalence of periodontal disease and its influencing factors were analyzed.
Results:
In the age group of 35-44, gingival bleeding was detected in 165 (93.75%) cases and dental calculus was detected in 176 (100.00%) cases; in the age group of 45-64, gingival bleeding was detected in 163 (93.14%) cases and dental calculus was detected in 161 (92.00%) cases; in the age group of 65-74, gingival bleeding was detected in 150 (88.24%) cases and dental calculus was detected in 162 (95.29%) cases. There were statistically significant differences in the detection rates of shallow periodontal pockets, deep periodontal pockets, and loss of periodontal attachment among the three groups (P<0.05). There wasalso asignificant difference in the detection rate of periodontitis among the three groups (P<0.05). Univariate analysis showed that gender, age, place of residence, smoking, alcohol consumption, brushing frequency, and dental cleaning in the past year were all associated with the occurrence of periodontitis (P<0.05). Logistic multi-factor regression analysis showed that age was a risk factor for the development of periodontitis in middle-aged and elderly patients (P<0.05).
Conclusion:
The prevalence of periodontal disease in middle-aged and elderly individuals is high, with a high prevalence of gingival bleeding and shallow periodontal pockets. Age is an influencing factor on the incidence of periodontitis in middle-aged and elderly individuals.
Background:
to determine the prevalence of periodontitis and if poor glycemic control is associated with increasing prevalence of the disease.
Methods:
This was a cross-sectional study involving children and adolescents with type 2 diabetes. A questionnaire related to oral health care history and oral health behaviors was administered to each participant and they then underwent a full mouth oral evaluation. In addition, clinical and metabolic parameters were extracted from the clinical chart.
Results:
121 children and adolescents (8 - 17 years, 11months) participated. Overall, 45.5% presented some degree of periodontitis, with 10 (8.3%) mild, 36 (29.8%) moderate and 9 (7.4%) severe. The periodontitis group (PD-group) had higher mean gingival and plaque indexes, periodontal probing depth and clinical attachment loss than the group without periodontitis (NoPD-group) (p<0.05). A statistically significant relationship between the prevalence of periodontitis and glycosylated hemoglobin (HbA1c) was verified in the bivariate (OR = 1.31, [CI 95% 1.13-1.53], p = 0.001) and multivariate (OR = 1.29, [CI 95% 1.03-1.61], p = 0.03) analysis. For the adjustment variables, associations were verified for duration of diabetes, age, BMIz, lack of running water, insulin use and acanthosis nigricans.
Conclusions:
Children and adolescents with type 2 diabetes presented high rates of periodontitis comparable to that seen in previous studies with youth with diabetes. Uncontrolled HbA1c influences prevalence of periodontal disease. The lack of matched control group and radiographs are limitations of the study. Comprehensive periodontal examination is essential for children and adolescents with type 2 diabetes to prevent, identify and treat periodontitis early. This article is protected by copyright. All rights reserved.