Constructing Interfacial Charge Transfer Channels and Electric Field in Violet Phosphorus-Based van der Waals Heterojunction for Phototherapy of Periodontitis.

Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.

Comparison of the effectiveness of Morus alba and chlorhexidine gels as an adjunct to scaling and root planing on stage II periodontitis - A randomized controlled clinical trial.

OBJECTIVES: The present study aimed to assess and compare the effect of Morus alba and chlorhexidine gel as an adjunct to scaling and root planing (SRP) in treating stage II periodontitis. METHODS: A single-blind, randomized controlled trial was conducted on 180 patients with stage II periodontitis who received full-mouth SRP. They were randomly assigned to receive chlorhexidine digluconate (CHX) gel, Morus alba (MA) and placebo gel for Groups A, B and C, respectively, at the baseline, 15 days and 30 days. Plaque index (PI), Gingival index (GI), periodontal pocket depth (PPD) and quantitative analysis (culture) of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia were assessed at baseline and 45 days. Analysis of variance was used to compare the significant difference in PI, GI, PPD and microbiological parameters between the three groups after the intervention, followed by post hoc Mann-Whitney U and Tukey's HSD test for clinical and microbiological parameters, respectively. RESULTS: Intergroup comparison of the PI, GI and microbiological parameters between the MA and CHX groups at the end of 45 days did not show a statistically significant difference (p > 0.05), whereas a statistically significant difference was observed for PPD between MA and CHX groups with the mean difference of 0.18 mm (p = 0.002). CONCLUSION: Morus alba gel was found to be effective in decreasing PPD. However, there was no difference between Morus alba and chlorhexidine gel as an adjunct to SRP in treating stage II periodontitis.

Does crocin create new hope for the treatment of oral problems? A focus on periodontitis.

According to the World Health Organization (WHO) reports, oral health has an indispensable role in the maintenance of human public health. However, oral problems, especially periodontitis, are known as bad players in this issue. Periodontitis, as the most prevalent oral disease, is a type of chronic illness mediated by bacterial pathogens and immune system reactions, which is linked with the destruction of tooth-protecting tissues, such as alveolar bone and periodontal ligament. Periodontitis has a high prevalence (over 40% in the United States) and can be associated with other systemic ailments, for instance, arthritis, osteoporosis, metabolic syndrome, cancer, respiratory diseases, chronic kidney disease, and Alzheimer's disease. The common treatments for periodontitis are classified into invasive (surgical) and noninvasive (antibiotic therapy, scaling, and root planning) methods; however, these therapies have not reflected enough effectiveness for related patients. New documents inform the beneficial effects of plant-based compounds in healing various disorders, like periodontitis. In conjunction with this subject, it has been revealed that crocin, as an active component of saffron, regulates the balance between osteoclasts and osteoblasts and has a stroking role in the accumulation of the most common collagen in teeth and bone (type 1 collagen). Besides, this carotenoid compound possesses anti-inflammatory and anti-oxidative effects, which can be associated with the therapeutic processes of crocin in this oral disease. Hence, this narrative review study was performed to reflect the reparative/regenerative aspects of crocin agonist periodontitis.

Superhydrophobic Tipped Antimicrobial Photodynamic Therapy Device for the In Vivo Treatment of Periodontitis Using a Wistar Rat Model.

Limited options exist for treatment of periodontitis; scaling and root planing (SRP) are not sufficient to eradicate P. gingivalis and the resulting inflammatory disease. Chlorhexidine (CHX), used as an adjuvant to SRP, may reduce bacterial loads but leads to pain and staining, while evidence for its efficacy is lacking. Antibiotics are effective but can lead to drug-resistance. The rising concern of antibiotic resistance limits the future use of this treatment approach. This study evaluates the efficacy of a novel superhydrophobic (SH) antimicrobial photodynamic therapy (aPDT) device as an adjuvant to SRP for the treatment of periodontitis induced in a Wistar rat in vivo model relative to CHX. The SH-aPDT device comprises an SH silicone rubber strip coated with verteporfin photosensitizer (PS), sterilized, and secured onto a tapered plastic optical fiber tip connected to a red diode laser. The superhydrophobic polydimethylsiloxane (PDMS) strips were fabricated by using a novel soluble template method that creates a medical-grade elastomer with hierarchical surface roughness without the use of nanoparticles. Superhydrophobicity minimizes direct contact of the PS-coated surface with bacterial biofilms. Upon insertion of the device tip into the pocket and energizing the laser, the device generates singlet oxygen that effectively targets and eliminates bacteria within the periodontal pocket. SH-aPDT treatment using 125 J/cm2 of red light on three consecutive days reduced P. gingivalis significantly more than SRP-CHX controls (p < 0.05). Clinical parameters significantly improved (p < 0.05), and histology and stereometry results demonstrated SH-aPDT to be the most effective treatment for improving healing and reducing inflammation, with an increase in fibroblast cells and extracellular matrix and a reduction in vascularization, inflammatory cells, and COX-2 expression. The SH-aPDT approach resulted in complete disease clearance assessed 30 days after treatment initiation with significant reduction of the periodontal pocket and re-formation of the junctional epithelium at the enamel-cementum junction. PS isolation on a SH strip minimizes the potential for bacteria to develop resistance, where the treatment may be aided by the oxygen supply retained within the SH surface.

An update on possible alternative therapeutics for future periodontal disease management.

Periodontitis is an inflammatory disease caused by microbial infections of the gum. At an advanced stage, periodontitis can even destroy the alveolar bone. Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Capnocytophaga gingivalis, and Pr. nigrescens are the major pathogens in periodontitis. Scaling and root planning are used together with local or systemic antibiotics to treat periodontitis. The difficulty in complete eradication of periodontal pathogens frequently leads to the relapse of the disease. As not many new antibiotics are available in the market, many researchers are now focusing on developing alternative strategies against periodontal microbes. This review provides an overview of the possible use of bacteriophages, lysins, honey, plant extracts, metallic salts, nanoparticles, and vaccines as alternative therapeutic agents against periodontal infections. The information provided here could help in designing alternative therapeutics for the treatment of periodontal infections.

Near-Infrared-Enhanced Dual Enzyme-Mimicking Ag-TiO2-x@Alginate Microspheres with Antibactericidal and Oxygeneration Abilities to Treat Periodontitis.

The effective treatment for periodontitis is to completely and sustainedly eradicate the bacterial pathogens from the complex periodontal pockets. Local sustained-release antibiotics as a complementary treatment after scaling and root planning can sustainedly combat bacterial pathogens in the periodontal pockets to help treat the disease, but the increasing concern of bacterial resistance limits its future use. Here, we reported a local antibacterial system based on microsized multifunctional Ag-TiO2-x encapsulated in alginate (ATA) microspheres. We confirmed that ATA displayed strong photothermally enhanced dual enzyme-mimicking (peroxidase-like and catalase-like) activities and weak photocatalytic activity under 808 nm near-infrared (NIR) irradiation, which could boost the generation of reactive oxygen species (ROS) and O2 in the presence of low-level H2O2. As a result, the ATA/H2O2/NIR system exhibited efficient antibacterial activity against Porphyromonas gingivalis and Streptococcus gordonii in both planktonic and biofilm forms. With the help of ROS, ATA could release Ag+ in concentrations sufficient to inhibit periodontal pathogens as well. Moreover, the in situ-generated oxygen was supposed to alleviate the local hypoxic environment and would help downregulate the lipopolysaccharide-mediated inflammatory response of periodontal stem cells. The in vivo rat periodontitis treatment results demonstrated that the ATA/H2O2/NIR system reduced the bacterial load, relieved inflammation, and improved tissue healing. Our work developed a new local prolonged bactericidal and oxygenation system for enhanced periodontitis. Avoiding the usage of antibiotics and nanomaterials, this strategy showed great promise in adjunctive periodontitis treatment and also in other biomedical applications.

Concise evaluation and therapeutic guidelines for severe periodontitis: A public health perspective.

The main goal of periodontology is to prevent and arrest gingivitis and periodontitis to avoid tooth loss and focal infection of periodontal origin. Periodontal scaling or flap surgery of moderate-to-severe periodontitis have shortcomings, most likely because removal of herpesviruses and bacterial pathogens in deep periodontal lesions and the adjacent inflamed gingiva requires systemic antimicrobial treatment (or gingivectomy). Valacyclovir (1000 mg twice daily on day 1, and 500 mg twice daily on day 2 and on day 3) is a potent anti-herpesvirus agent. Antibiotic combinations against bacterial pathogens include amoxicillin-metronidazole (250 mg of each, thrice daily for 4 days; for systemically healthy adults) and ciprofloxacin-metronidazole (500 mg of each, twice daily for 4 days; for immunosuppressed individuals and patients exposed to contaminated water and poor sanitation). Supportive antiseptic treatment may consist of 0.1%-0.2% sodium hypochlorite (regular household bleach) as cooling spray in ultrasonic scalers, flosser fluid in oral irrigators, and mouthrinse in patient self-care. The anti-infective treatment described here helps control cases of severe periodontitis and constitutes an exceedingly inexpensive alternative to conventional (mechanical) periodontal therapy.

Oral microbiota associated with gingiva of healthy, gingivitis and periodontitis cases.

Oral microbes coexist with each other in a symbiotic relationship or as commensals in healthy body. Teeth and oral cavity harbor diverse community of fungi and bacteria. This study focused on bacterial and fungal component of gingiva, where the last occupy little attention. In addition to study the antimicrobial activity of toothpastes, mouth washes and natural oils against microorganisms. Sixty swabs from outer surfaces of gingiva in healthy persons, as well as patients complaining of gingivitis and periodontitis were collected for fungal and bacterial analyses. Sensitivity of the isolated microorganisms to some pharmaceutical preparations and natural oils was also performed. Ten fungal and 9 bacterial species were identified. There is a highly significant variation in the frequency of Klebsiella pneumonia among healthy, gingivitis and periodontitis. Also, Candida tropicalis and cocci bacteria showed significant diversity among the three tested groups. Among pharmaceutical preparations (toothpastes and mouth washes) and natural oils, Paradontax, Hexitol and clove oil showed the best antimicrobial activity against tested fungal and bacterial strains. Although, minimum inhibition concentrations (MICs) of clove oil were high compared to Paradontax and Hexitol, nevertheless, it is highly recommended as both antifungal and antibacterial agent against oral pathogenic microorganisms, because it is a natural compound and nearly devoid of side effects.

Synergistic antibacterial activity of herbal extracts with antibiotics on bacteria responsible for periodontitis.

INTRODUCTION: Development of bacterial resistance and antimicrobial side-effect has shifted the focus of research toward Ethnopharmacology. A biologically active compound derived from the plants may increase the effectiveness of antibiotic when used in combination. The present study aims to determine the synergistic antibacterial effect of ethanolic extracts of Punica granatum (pericarp), Commiphora molmol, Azadirachta indica (bark) in combination with amoxicillin, metronidazole, tetracycline, and azithromycin on periodontopathic bacteria: Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitans. METHODOLOGY: Periodontopathic bacterial strains were isolated from the plaque sample that was collected from periodontitis patients and grown under favorable conditions. Susceptibility of bacteria to the antibiotics and extracts was determined by disc diffusion method by measuring the diameter of the inhibition zones. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of plant extracts were evaluated against each bacterium. Synergistic effect of plant extract in combination with antibiotics was tested against each bacterium by measuring the diameter of zone of inhibition (ZOI). RESULTS: Findings revealed that all plant extracts exhibited an inhibitory effects on the proliferation and growth of periodontopathic bacteria. The maximum antibacterial effect was exhibited by C. molmol on P. gingivalis (ZOI = 20 ± 0.55 mm, MIC = 0.53 ± 0.24 mg/mL and MBC = 5.21 ± 1.81 mg/mL) (p < 0.05), meanwhile, no antibacterial activity was exhibited by P. granatum on T. forsythia. Synergistic antibacterial effect was recorded when plant extracts were used in combination with antibiotics. The best synergism was exhibited by P. granatum with amoxicillin against A. actinomycetemcomitans (24 ± 1.00 mm) (p < 0.05). CONCLUSIONS: The synergistic test showed significant antibacterial activity when plant extracts were combined with antibiotics against all the experimented bacteria.

Gellan Gum-Based Bilayer Mucoadhesive Films Loaded with Moxifloxacin Hydrochloride and Clove Oil for Possible Treatment of Periodontitis.

BACKGROUND/OBJECTIVE: Periodontitis is a widely spread oral infection and various antibiotics are utilized for its treatment, but high oral doses and development of antibiotic resistance limit their use. This study was aimed at development of natural polymer-based mucoadhesive bilayer films loaded with moxifloxacin hydrochloride (Mox) and clove essential oil (CEO) to potentially combat bacterial infection associated with periodontitis. METHODS: Films were synthesized by double solvent casting technique having an antibiotic in the gellan gum-based primary layer with clove oil in a hydroxyethyl cellulose-based secondary layer. RESULTS: Prepared films were transparent, flexible, and showed high antibacterial response against both gram-positive and gram-negative bacteria. The films showed excellent pharmaceutical attributes in terms of drug content, folding endurance, swelling index, and mucoadhesive strength. Solid state characterization of formulation showed successful incorporation of drug and oil in separate layers of hydrogel structure. An in-vitro release study showed an initial burst release of drug followed by sustained release for up to 48 hours. CONCLUSION: The prepared mucoadhesive bilayer buccal films could be used as a potential therapeutic option for the management of periodontitis.

Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model.

Periodontal infection induces systemic inflammation; therefore, aggravating diabetes. Orally administered periodontal pathogens may directly alter the gut microbiota. We orally treated obese db/db diabetes mice using Porphyromonas gingivalis (Pg). We screened for Pg-specific peptides in the intestinal fecal specimens and examined whether Pg localization influenced the intestinal microbiota profile, in turn altering the levels of the gut metabolites. We evaluated whether the deterioration in fasting hyperglycemia was related to the changes in the intrahepatic glucose metabolism, using proteome and metabolome analyses. Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05), with a significant (P < 0.01) increase in dental alveolar bone resorption. Pg-specific peptides were identified in fecal specimens following oral Pg treatment. The intestinal Pg profoundly altered the gut microbiome profiles at the phylum, family, and genus levels; Prevotella exhibited the largest increase in abundance. In addition, Pg-treatment significantly altered intestinal metabolite levels. Fasting hyperglycemia was associated with the increase in the levels of gluconeogenesis-related enzymes and metabolites without changes in the expression of proinflammatory cytokines and insulin resistance. Oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thus aggravating hyperglycemia in an obese type 2 diabetes mouse model.

Green Synthesis of Copper Nano-Drug and Its Dental Application upon Periodontal Disease-Causing Microorganisms.

Dental pathogens lead to chronic diseases like periodontitis, which causes loss of teeth. Here, we examined the plausible antibacterial efficacy of copper nanoparticles (CuNPs) synthesized using Cupressus macrocarpa extract (CME) against periodontitis-causing bacteria. The antimicrobial properties of CME-CuNPs were then assessed against oral microbes (M. luteus. B. subtilis, P. aerioginosa) that cause periodontal disease and were identified using morphological/ biochemical analysis, and 16S-rRNA techniques. The CME-CuNPs were characterized, and accordingly, the peak found at 577 nm using UV-Vis spectrometer showed the formation of stable CME-CuNPs. Also, the results revealed the formation of spherical and oblong monodispersed CME-CuNPs with sizes ranged from 11.3 to 22.4 nm. The FTIR analysis suggested that the CME contains reducing agents that consequently had a role in Cu reduction and CME-CuNP formation. Furthermore, the CME-CuNPs exhibited potent antimicrobial efficacy against different isolates which was superior to the reported values in literature. The antibacterial efficacy of CME-CuNPs on oral bacteria was compared to the synergistic solution of clindamycin with CME-CuNPs. The solution exhibited a superior capacity to prevent bacterial growth. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and fractional inhibitory concentration (FIC) of CME-CuNPs with clindamycin recorded against the selected periodontal disease-causing microorganisms were observed between the range of 2.6-3.6 µg/ml, 4-5 µg/ml and 0.312-0.5, respectively. Finally, the synergistic antimicrobial efficacy exhibited by CME-CuNPs with clindamycin against the tested strains could be useful for the future development of more effective treatments to control dental diseases.

PHoral: Effects of carnosine supplementation on quantity/quality of oral salivae in healthy volunteer and in subjects affected by common oral pathologies.

BACKGROUND: Diseases of the oral cavity (OC) with an infectious trigger such as caries and periodontal disease are extremely common in the general population and can also have effects at the cardiovascular level. The oral salivary flow, with its buffering capacity, is able to regulate the pH of the OC and, therefore, significantly contribute to the ecological balance of the microenvironment in which the oral microbiome (OM) develops. On the other side, when the quality/quantity of salivary flow is altered it is supposed the disruption of this balance with the potential increase in oral pathogens and triggered diseases. Among the endogenous substances able to exert a significant effect on the salivary flow and its characteristics, carnosine (Car), a dipeptide originally isolated in skeletal muscle, represents, thanks to the known buffering properties, a promising principle. METHODS: We aimed this protocol to evaluate the quantitative/qualitative characteristics of the salivary flow in healthy volunteer subjects (n = 20) and in subjects suffering from common OC pathologies (n = 40), before and after 7 days of supplementation with SaliflussTM (Metis Healthcare srl, Milan, Italy), a Class I medical device on the market as 400 mg mucoadhesive oral tablets that has Car as the main ingredient. DISCUSSION: Combining the characteristics of saliva with the OM and comparing them with OC pathologies, we expect to clarify their reciprocal relationship and, using quantitative proteomics techniques, to help clarify the mechanism of action of Car.

Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis.

The development of a targeted therapy would significantly improve the treatment of periodontitis and its associated diseases including Alzheimer's disease, rheumatoid arthritis, and cardiovascular diseases. Glutaminyl cyclases (QCs) from the oral pathogens Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia represent attractive target enzymes for small-molecule inhibitor development, as their action is likely to stabilize essential periplasmic and outer membrane proteins by N-terminal pyroglutamination. In contrast to other microbial QCs that utilize the so-called type I enzymes, these oral pathogens possess sequences corresponding to type II QCs, observed hitherto only in animals. However, whether differences between these bacteroidal QCs and animal QCs are sufficient to enable development of selective inhibitors is not clear. To learn more, we recombinantly expressed all three QCs. They exhibit comparable catalytic efficiencies and are inhibited by metal chelators. Crystal structures of the enzymes from P. gingivalis (PgQC) and T. forsythia (TfQC) reveal a tertiary structure composed of an eight-stranded ß-sheet surrounded by seven α-helices, typical of animal type II QCs. In each case, an active site Zn ion is tetrahedrally coordinated by conserved residues. Nevertheless, significant differences to mammalian enzymes are found around the active site of the bacteroidal enzymes. Application of a PgQC-selective inhibitor described here for the first time results in growth inhibition of two P. gingivalis clinical isolates in a dose-dependent manner. The insights gained by these studies will assist in the development of highly specific small-molecule bacteroidal QC inhibitors, paving the way for alternative therapies against periodontitis and associated diseases.

Oleoresins and naturally occurring compounds of Copaifera genus as antibacterial and antivirulence agents against periodontal pathogens.

Invasion of periodontal tissues by Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans can be associated with aggressive forms of periodontitis. Oleoresins from different copaifera species and their compounds display various pharmacological properties. The present study evaluates the antibacterial and antivirulence activity of oleoresins obtained from different copaifera species and of ten isolated compounds against two causative agents of periodontitis. The following assays were performed: determination of the minimum inhibitory concentration (MIC), determination of the minimum bactericidal concentration (MBC), and determination of the antibiofilm activity by inhibition of biofilm formation and biofilm eradication tests. The antivirulence activity was assessed by hemagglutination, P. gingivalis Arg-X and Lis-X cysteine protease inhibition assay, and A. actinomycetemcomitans leukotoxin inhibition assay. The MIC and MBC of the oleoresins and isolated compounds 1, 2, and 3 ranged from 1.59 to 50 µg/mL against P. gingivalis (ATCC 33277) and clinical isolates and from 6.25 to 400 µg/mL against A. actinomycetemcomitans (ATCC 43717) and clinical isolates. About the antibiofilm activity, the oleoresins and isolated compounds 1, 2, and 3 inhibited biofilm formation by at least 50% and eradicated pre-formed P. gingivalis and A. actinomycetemcomitans biofilms in the monospecies and multispecies modes. A promising activity concerning cysteine protease and leucotoxin inhibition was also evident. In addition, molecular docking analysis was performed. The investigated oleoresins and their compounds may play an important role in the search for novel sources of agents that can act against periodontal pathogens.

Effects of a tart cherry (Prunus cerasus L.) phenolic extract on Porphyromonas gingivalis and its ability to impair the oral epithelial barrier.

Periodontal diseases, including gingivitis and periodontitis, are a global oral health problem. Porphyromonas gingivalis, a key pathogen involved in the onset of periodontitis, is able to colonize the subgingival epithelium and invade the underlying connective tissue due to the contribution of cysteine proteases known as gingipains. In this study, we investigated the effects of a phenolic extract prepared from tart cherry (Prunus cerasus L.) juice on the growth, adherence, and protease activity of P. gingivalis. We also assessed the protective effect of the tart cherry extract on the disruption of the oral epithelial barrier induced by P. gingivalis. The tart cherry extract that contains procyanidins and quercetin and its derivatives (rutinoside, glucoside) as the most important phenolic compounds attenuated P. gingivalis growth, reduced adherence to an experimental basement membrane matrix model, and decreased the protease activities of P. gingivalis. The tart cherry extract also exerted a protective effect on the integrity of the oral epithelial barrier in an in vitro model infected with P. gingivalis. More specifically, the extract prevented a decrease in transepithelial electrical resistance as well as the destruction of tight junction proteins (zonula occludens-1 and occludin). These results suggest that the tart cherry phenolic extract may be a promising natural product for the treatment of periodontitis through its ability to attenuate the virulence properties of P. gingivalis and curtail the ability of this pathogen to impair the oral epithelial barrier.

Anti-Periodontitis Effect of Ethanol Extracts of Alpinia Katsumadai Seeds.

Oral microbes are intimately associated with many oral and systemic diseases. Ongoing research is seeking to elucidate drugs that prevent and treat microbial diseases. Various functions of Alpinia Katsumadai seed extracts have been reported such as their anti-viral, anti-oxidant, anti-inflammatory, anti-puritic, anti-emetic, and cytoprotective effects. Here, we investigated the anti-periodontitis effect of an ethanol extract of Alpinia Katsumadai seeds (EEAKSs) on dental plaque bacteria (DPB)-induced inflammation and bone resorption. DPB and Porphyromonas gingivalis (P. gingivalis) were cultured and lipopolysaccharide (LPS) was extracted. Prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX-2) levels were estimated using ELISA. Cytotoxicity was also verified. Proteases were screened using a protease antibody array method. Osteoclastic bone resorption was also investigated. EEAKSs suppressed P. gingivalis growth on agar plates. LPS prepared from dental plaque bacteria (DPB-LPS) and P. gingivalis (PG-LPS) significantly increased PGE2 and COX2 levels in immortalized gingival fibroblasts (IGFs), immortalized human oral keratinocytes (IHOKs), and RAW264.7 macrophage cells. However, DPB-LPS and PG-LPS-induced PGE2 and COX-2 increases were effectively abolished by EEAKS treatment at non-cytotoxic concentrations. In the protease antibody array, matrix metalloproteinase (MMP)-2, MMP-3, MMP-7, kallikrein 10, cathepsin D, and cathepsin V levels were increased by PG-LPS stimulation. However, increases in protease levels except for cathepsin D were suppressed by EEAKS treatment. In addition, RANKL-induced osteoclast differentiation was significantly inhibited by EEAKS treatment, leading to reductions in resorption pit formation. These results suggest that EEAKSs exerted a beneficial oral health effect to help prevent DPB-mediated periodontal disease.

Spirulina maxima reduces inflammation and alveolar bone loss in Porphyromonas gingivalis-induced periodontitis.

BACKGROUND: Periodontitis is a common oral disease characterized as inflammation on gingival tissue and alveolar bone resorption. Spirulina maxima has been reported to have anti-oxidative and anti-inflammatory effects on gastric ulcers. However, its effects on gingival inflammation and alveolar bone resorption of periodontitis have not been studied. PURPOSE: This study was designed to investigate the effects of S. maxima on the P. gingivalis-induced periodontitis and to elucidate its mechanism. METHODS: The phycocyanin contents in S. maxima were identified by high-performance liquid chromatography. 8-week old SD rats were induced periodontitis by inoculation with P. gingivalis for 14 days. The rats were then orally treated with S. maxima 100, 200, 400 mg/kg, or indomethacin (IND, positive control) 5 mg/kg for an additional 14 days. Inflammatory responses, expressions of collagenases in gingival tissue, osteoclast formation and activation, alveolar bone resorption, osteogenesis-related markers, and BMP2/Smad signaling in alveolar bone were measured. RESULTS: Pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and inflammatory transcription factor NF-κB were decreased in gingival tissue by S. maxima administration. Also, myeloperoxidase (MPO) activity and matrix metalloproteinase (MMPs) expression were decreased by S. maxima administration. Conversely, S. maxima increased IL-4, anti-inflammatory cytokine from Th2 cells. The osteoprotegerin (OPG) / receptor activator of NF-κB ligand (RANKL) expression ratio, which represents osteoclast-osteoblast balance, was increased in S. maxima-treated groups. The alveolar bone loss and the number of TRAP-positive osteoclast cells were also declined in S. maxima-treated groups while the osteoblasts count was increased. Besides, in S. maxima-treated groups, the osteogenesis-related factors were promoted and BMP-2/Smad pathway was up-regulated in a periodontitis condition. CONCLUSION: S. maxima reduces periodontitis induced by P. gingivalis through anti-inflammatory effect and resultant reduction in bone loss, suggesting that S. maxima might be a potential agent for treating periodontitis.

Effect of thymoquinone on Fusobacterium nucleatum­associated biofilm and inflammation.

Periodontitis affects oral tissues and induces systemic inflammation, which increases the risk of cardiovascular disease and metabolic syndrome. Subgingival plaque accumulation is a trigger of periodontitis. Fusobacterium nucleatum (FN) contributes to subgingival biofilm complexity by intercalating with early and late bacterial colonizers on tooth surfaces. In addition, inflammatory responses to FN are associated with the progression of periodontitis. Nigella sativa Lin. seed, which is known as black cumin (BC), has been used as a herbal medicine to treat ailments such as asthma and infectious diseases. The current study examined the inhibitory effect of BC oil and its active constituents, thymol (TM) and thymoquinone (TQ), on FN­associated biofilm and inflammation. FN­containing biofilms were prepared by co­cultivation with an early dental colonizer, Actinomyces naeslundii (AN). The stability and biomass of FN/AN dual species biofilms were significantly higher compared with FN alone. This effect was retained even with prefixed cells, indicating that FN/AN co­aggregation is mediated by physicochemical interactions with cell surface molecules. FN/AN biofilm formation was significantly inhibited by 0.1% TM or TQ. Confocal laser scanning microscopy indicated that treatment of preformed FN/AN biofilm with 0.01% of BC, TM or TQ significantly reduced biofilm thickness, and TQ demonstrated a cleansing effect equivalent to that of isopropyl methylphenol. TQ dose­dependently suppressed TNF­α production from a human monocytic cell line, THP­1 exposed to FN, yet showed no toxicity to THP­1 cells. These results indicated that oral hygiene care using TQ could reduce FN­associated biofilm and inflammation in gingival tissue.

Antibacterial and anti-inflammatory activities of cardamom (Elettaria cardamomum) extracts: Potential therapeutic benefits for periodontal infections.

Cardamom (Elettaria cardamomum) is a traditional aromatic plant for which several pharmacological properties have been associated. In this study, the antibacterial activity of two cardamom extracts (fruit and seeds), rich in volatile compounds, against major periodontal pathogens was evaluated. Moreover, the ability of the extracts to exert anti-inflammatory activity was tested. Both cardamom fruit and seed extracts exerted an antibacterial effect against Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, and Prevotella intermedia (minimum inhibitory concentrations: 0.5% [v/v], 0.25%, 0.062%, 0.125%, respectively and minimum bactericidal concentrations: 1%, 0.25%, 0.062%, 0.25%, respectively). The cell membrane of P. gingivalis was disrupted by a treatment with cardamom extracts suggesting the bactericidal mode of action. The extracts also inhibited biofilm formation although it correlated with a growth reduction. Moreover, the cardamom extracts significantly decreased the secretion of IL-1ß, TNF-α, and IL-8 by lipopolysaccharide-stimulated macrophages. Evidence were brought that the anti-inflammatory activity may result from inhibition of the NF-κB signaling pathway. This study is the first to provide evidence that cardamom fruit and seed extracts through their antibacterial and anti-inflammatory properties may be therapeutic agents of interest against periodontal infections.