curcumin and Periodontitis

Curcumin is a natural herb and polyphenol that is obtained from the medicinal plant Curcuma longa. It's anti-bacterial, anti-inflammatory, anti-cancer, anti-mutagenic, antioxidant and antifungal properties can be leveraged to treat a myriad of oral and systemic diseases. However, natural curcumin has weak solubility, limited bioavailability and undergoes rapid degradation, which severely limits its therapeutic potential. To overcome these drawbacks, nanocurcumin (nCur) formulations have been developed for improved biomaterial delivery and enhanced treatment outcomes. This novel biomaterial holds tremendous promise for the treatment of various oral diseases, the majority of which are caused by dental biofilm. These include dental caries, periodontal disease, root canal infection and peri-implant diseases, as well as other non-biofilm mediated oral diseases such as oral cancer and oral lichen planus. A number of in-vitro studies have demonstrated the antibacterial efficacy of nCur in various formulations against common oral pathogens such as S. mutans, P. gingivalis and E. faecalis, which are strongly associated with dental caries, periodontitis and root canal infection, respectively. In addition, some clinical studies were suggestive of the notion that nCur can indeed enhance the clinical outcomes of oral diseases such as periodontitis and oral lichen planus, but the level of evidence was very low due to the small number of studies and the methodological limitations of the available studies. The versatility of nCur to treat a diverse range of oral diseases augurs well for its future in dentistry, as reflected by rapid pace in which studies pertaining to this topic are published in the scientific literature. In order to keep abreast of the latest development of nCur in dentistry, this narrative review was undertaken. The aim of this narrative review is to provide a contemporaneous update of the chemistry, properties, mechanism of action, and scientific evidence behind the usage of nCur in dentistry.

Topics: Anti-Inflammatory Agents; Biocompatible Materials; Curcumin; Dental Caries; Dentistry; Humans; Lichen Planus, Oral; Periodontitis

Phenolic compounds are natural phytochemicals that have recently reported numerous health benefits. Resveratrol, curcumin, and quercetin have recently received the most attention among these molecules due to their documented antioxidant effects. The review aims to investigate the effects of these molecules on bone metabolism and their role in several diseases such as osteopenia and osteoporosis, bone tumours, and periodontitis. The PubMed/Medline, Web of Science, Google Scholar, Scopus, Cochrane Library, and Embase electronic databases were searched for papers in line with the study topic. According to an English language restriction, the screening period was from January 2012 to 3 July 2022, with the following Boolean keywords: ("resveratrol" AND "bone"); ("curcumin" AND "bone"); ("quercetin" AND "bone"). A total of 36 papers were identified as relevant to the purpose of our investigation. The studies reported the positive effects of the investigated phenolic compounds on bone metabolism and their potential application as adjuvant treatments for osteoporosis, bone tumours, and periodontitis. Furthermore, their use on the titanium surfaces of orthopaedic prostheses could represent a possible application to improve the osteogenic processes and osseointegration. According to the study findings, resveratrol, curcumin, and quercetin are reported to have a wide variety of beneficial effects as supplement therapies. The investigated phenolic compounds seem to positively mediate bone metabolism and osteoclast-related pathologies.

Topics: Curcumin; Dietary Supplements; Humans; Osteoporosis; Periodontitis; Quercetin; Resveratrol

Curcumin (CUR) has been used clinically in several studies as a subgingival irrigant or as a photoantimicrobial in combination with a blue light-emitting diode (LED) in antimicrobial photodynamic therapy (aPDT) adjuvant to scaling and root planing (SRP). The aim of this study was to assess the effectiveness of CUR as an irrigant or as a photoantimicrobial in conjunction with the blue LED in aPDT adjuvant to SRP, compared to SRP as conventional mechanical treatment.. Fifteen randomized controlled trials (RCT) were included in a qualitative analysis after researching the databases: PubMed / MEDLINE, SCOPUS, EMBASE, Cochrane Central, Web of Science and Scielo. Manual searches were also performed. Five studies were submitted to quantitative analysis, evaluating periodontal clinical parameters such as probing depth (PD) and clinical attachment level (CAL).. The obtained results have shown clinical benefits in PD reduction and CAL gains at 3 months with the use of CUR as adjuvant therapy to SRP, both as an irrigant or photoantimicrobial, in comparison with SRP monotherapy.. Currently, there is evidence that treatment with CUR applied as irrigant or in conjunction with the blue LED as aPDT presents superior clinical results in the short term, for clinical periodontics parameters like as PD reduction and CAL gain, when compared to SRP monotherapy in the non-surgical treatment of periodontitis. However, these results cannot be proven in the long term.

Topics: Chronic Periodontitis; Curcumin; Dental Scaling; Humans; Periodontitis; Photochemotherapy; Photosensitizing Agents; Root Planing

Curcumin is the main active ingredient of turmeric, which has a wide range of pharmacological effects, including antitumor, antibacterial, anti-inflammatory, anti-oxidation, immune regulation, and so on. Periodontitis is a prevalent oral inflammatory disease caused by a variety of factors. In recent years, many studies have shown that curcumin has a potential role on the treatment of periodontitis. Curcumin has been used in research related to the treatment of periodontitis in the form of solution, chip, gel, and capsule. Combined with other periodontitis treatment methods, such as scaling and root planing (SRP) and photodynamic therapy (PDT), can enhance curcumin's efficacy in treating periodontitis. In addition to natural curcumin, chemically modified curcumin, such as 4-phenylaminocarbonyl bis-demethoxy curcumin (CMC 2.24) and 4-methoxycarbonyl curcumin (CMC 2.5), have also been used in animal models of periodontitis. Here, this paper reviews the research progress of curcumin on the treatment of periodontitis and its related mechanisms.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Dental Scaling; Periodontitis; Root Planing

Periodontitis is a chronic inflammatory disease characterized by destruction of the supporting structures of teeth caused by development of dental plaques and accumulation of microorganism around the gingival tissue. Curcumin has been shown to improve clinical parameters in periodontal diseases. However, the efficacy of curcumin in the elimination of periodontal pathogens is not clearly defined. The purpose of this study was to carry out a systematic review of the antibacterial activity of curcumin against periodontal pathogens. An electronic literature search in Medline, Scopus, Science Direct, Web of Science, Cochrane library, and Google scholar was performed up to February 29, 2020, to identify studies assessing the antibacterial activity of curcumin against periodontal pathogens. From 1238 publications, three clinical trials and five in vitro studies met the eligibility criteria. All three clinical studies reported improvement in restoring gingival health in clinical and microbiological parameters, following adjunctive use of curcumin for treatment of periodontitis. All five in vitro studies showed that curcumin could inhibit the growth of bacterial strains. Three of the five in vitro studies evaluated the effect of curcumin on mixed biofilm of periopathogens, which showed a significant inhibitory effect of curcumin on periodontal biofilms. This systematic review found that curcumin has antibacterial activity against periopathogens. The anti-biofilm activity of curcumin is reported as one of the mechanisms for this phenomenon. Curcumin could improve the clinical parameters of periodontal tissue not only by inhibition of the pathogens but also by modulating the host response.

Topics: Anti-Bacterial Agents; Biofilms; Curcumin; Humans; Periodontal Diseases; Periodontitis

Periodontal disease is one of the most common causes of tooth loss among adults. Research shows that inflammation is one of the crucial components in the initiation and progression of periodontitis. Various herbal medicines have recently been receiving attention for the management of periodontitis owing to their general safety and efficacy. Curcumin, a bioactive polyphenol extracted from Curcuma longa, has been shown to possess antioxidant, antimicrobial, anti-inflammatory and analgesic properties. Several studies have assessed the efficacy of curcumin against periodontal diseases. These studies have shown equivalent or even higher efficacy of curcumin compared to the commonly used medications for the management of periodontitis such as chlorhexidine. Herein, we review the experimental and clinical findings on the anti-periodontitis effects of curcumin and the pharmacological mechanisms underlying these effects.

Topics: Adult; Anti-Inflammatory Agents; Chlorhexidine; Curcumin; Humans; Inflammation; Periodontal Diseases; Periodontitis

Curcumin is a plant-derived polyphenol extracted from the rhizome of turmeric. As curcumin has such favorable properties as anti-inflammation, anti-oxidation, anti-angiogenesis, immune regulation, anti-bacterial and pro-apoptosis and showed few side effects, the application of curcumin in prevention and treatment of periodontal diseases is promising. This article reviewed the research progress of curcumin in the prevention and treatment of periodontitis.. 姜黄素是一种从姜黄根茎中提取的天然植物类多酚。由于姜黄素具有抗炎、抗氧化、抗血管生成、免疫调节、抑菌和促进细胞凋亡等多种生物学作用，且安全无毒，不良反应小，使其在牙周病预防和治疗中具有潜在的应用前景。本文就近年来姜黄素在牙周炎防治方面的相关研究进展做一综述。.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Inflammation; Periodontitis

We propose curcumin as a preventive measure to avoid/manage periodontitis (PD), and as a natural immunosuppressant for rheumatoid arthritis (RA). PD, mainly caused by

Topics: Animals; Anti-Bacterial Agents; Anti-Citrullinated Protein Antibodies; Antirheumatic Agents; Arthritis, Rheumatoid; Curcumin; Disease Models, Animal; Humans; Immunosuppressive Agents; Periodontitis; Phytotherapy; Plant Extracts; Plants, Medicinal; Porphyromonas gingivalis; Risk Factors; T-Lymphocytes, Regulatory; Th17 Cells

Assess a single local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing (SRP) in nonsurgical periodontal treatment (NPT).. Twenty healthy subjects with periodontitis received SRP+PLGA/PLA nanoparticles loaded with 50 μg of curcumin (N-Curc) or SRP+empty nanoparticles. Probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were monitored at baseline, 30, 90, and 180 days. IL-1α, IL-6, TNFα, and IL-10 in the gingival crevicular fluid (GCF) were assessed by ELISA, and counts of 40 bacterial species were determined by DNA hybridization at baseline, 3, 7, and 15 days post-therapy.. PPD, CAL, and BOP were similarly and significantly improved in both experimental groups. There was no difference in GCF cytokine levels between experimental groups, although IL-6 was decreased at 3 days only in the N-Curc group. NPT reduced counts of red complex bacterial species in both groups. Veillonella Parvula counts increased significantly only in N-Curc group at 7 days, whereas Aggregatibacter actinomycetemcomitans counts increased significantly only in the control group from day 3 to day 15.. We conclude that a single local administration of nanoencapsulated curcumin in periodontally diseased sites had no additive benefits to NPT.. Our results showed that a single local application of curcumin-loaded nanoparticles associated with nonsurgical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy.

Topics: Chronic Periodontitis; Curcumin; Dental Scaling; Follow-Up Studies; Gingival Crevicular Fluid; Humans; Nanoparticles; Periodontitis; Root Planing; Veillonella

The aim was to assess the influence of local application of curcumin-loaded nanoparticles on an experimental model of periodontal repair. Periodontitis was induced by ligatures on both lower first molars of rats. After 15 days, ligatures were removed ("treatment") and animals were randomly allocated to three experimental groups (n = 8/group): (i) 0.05 mg/ml curcumin-loaded nanoparticles, (ii) empty nanoparticles (vehicle control), and (iii) sterile saline (negative control). Experimental treatments were administered locally on days 0, 3, 5, 7, 9, and 11 after ligature removal. Animals were euthanized at 7 and 14 days. Bone repair was assessed by microcomputer tomography (µCT). Histological sections were stained with hematoxylin/eosin (H/E), Picrosirius Red, and Masson's trichrome. Expression of Runx-2 was studied by immunohistochemistry. Gene expression of Itgam, Arg1, and Inos was assessed by RT-qPCR. At 7 days, there was increased gene expression of Itgam and Arg1 and of the relative expression of Arg1/Inos in curcumin-treated animals, but no difference in any other outcomes. At 14 days, curcumin-loaded nanoparticles significantly increased bone repair and collagen content, as well as the number of osteocytes, percentage of extracellular matrix, and expression of Runx2. The results demonstrate that local administration of curcumin-loaded nanoparticles enhanced tissue repair in an experimental model of periodontal repair. Nanoparticle-encapsulated curcumin enhances early post-treatment repair of periodontal tissues.

Topics: Alveolar Bone Loss; Animals; Curcumin; Nanoparticles; Periodontitis; Rats

This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology.. Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis.. A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets.. The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.

Topics: Curcumin; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Molecular Docking Simulation; Network Pharmacology; Periodontitis

Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of

Topics: Animals; Biological Assay; Curcumin; Ferroptosis; Glutathione; Mice; Periodontitis; Regulated Cell Death

Periodontitis is a chronic oral disease prevalent worldwide, and natural products are recommended as adjunctive therapy due to their minor side effects. Curcumin, a widely used ancient compound, has been reported to possess therapeutic effects in periodontitis. However, the exact mechanism underlying its activity remains unclear. In this context, the present study aimed to conduct computational simulations to uncover the potential mechanism of action of Curcumin in the treatment of periodontitis.. Single-cell analysis was conducted using a dataset (i.e., GSE164241) curated from the Gene Expression Omnibus (GEO) database through an R package "Seurat package." Bulk RNA sequencing data were curated from GSE10334 and GSE16134 and processed by R package "Limma." Then, the marker genes in the single-cell transcriptome and differentially expressed genes (DEGs) in the bulk transcriptome were integrated. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were also carried out to reveal their functionalities. Key targets were mined from their protein-protein interaction (PPI) network topologically. Afterward, molecular docking was performed. The top-ranked pose was subjected to molecular dynamics simulations to investigate the stability of the docking result.. FOS, CXCL1, CXCL8, and IL1B, were filtered after a series of selected processes. The results of molecular modeling suggested that except for IL1B, the Vena Scores of the rest exceeded -5 kcal/mol. Furthermore, the molecular dynamic simulation indicated that the binding of the CXCL8-Curcumin complex was stable over the entire 100 ns simulation.. The present study unlocked the binding modes of CXCL1, FOS, and CXCL8 with the Curcumin molecule, which were relatively stable, especially for CXCL8, hindering its promising potential to serve as the critical targets of Curcumin in periodontitis treatment.

Topics: Computational Biology; Curcumin; Gene Expression Profiling; Humans; Molecular Docking Simulation; Periodontitis; Protein Interaction Maps

This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy.. 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.. 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.. 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.

Topics: Cell Membrane; Curcumin; Humans; Molecular Docking Simulation; Periodontitis; Receptors, Chemokine

This study aimed to evaluate the effect of curcumin gel on antioxidant marker level in experimental induced diabetes and periodontitis (EDP) in rats. Adult Wistar rats were randomized into five groups (20 each): (1) EDP treated with scaling and root planing (SRP) + curcumin gel (CU), (2) EDP treated with CU, (3) EDP treated with SRP, (4) EDP without treatment, and (5) systemically healthy and without ligature (control). Each group was subdivided equally into 4 subgroups of 5 rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ), and periodontitis was induced by a ligature. Blood samples were collected by cardiac puncture at 0, 7, 14, and 21 days to assess oxidative stress of malondialdehyde (MDA) and antioxidant enzymes of glutathione peroxidase (GPx), catalase (CAT), and suproxidase dismutase (SOD) levels. The results showed a significant increase in serum MDA and antioxidant enzyme levels in the untreated EDP group compared to the control group (

Topics: Animals; Antioxidants; Catalase; Curcumin; Diabetes Mellitus, Experimental; Glutathione Peroxidase; Oxidative Stress; Periodontitis; Rats; Rats, Wistar; Superoxide Dismutase

Topics: Animals; Curcumin; Cytokines; Interleukin-6; Male; Periodontitis; Rats; RNA, Messenger

Gingivitis can trigger gingival diseases such as periodontitis. Since the complete removal of microbial plaques by mechanical procedures is not conceivable in some conditions and also chemical mouthwashes have a lot of side effects, finding a new treatment strategy would be useful. In the present study, for the first time, the effects of oral nano-curcumin on gingival inflammation in patients with gingivitis and mild periodontitis were assessed. Forty eight patients with gingivitis and mild periodontitis participated in this clinical trial. In one group the patients were treated with Sina curcumin capsules 80 mg and the other group received a placebo. Clinical parameters, including modified gingival index, papillary bleeding index, and plaque index were determined on days 0, 7, 14, and 28. There were no significant differences in age, sex, papillary bleeding index (PBI), and modified gingival index (MGI) between the two groups at baseline. There was a dropout of two patients (both from the placebo group). The MGI and PBI have a significantly decreasing trend in both case and control groups and the decreases were severe in the case group. The differences between PBI and MGI in the two groups were significant at 14 and 28 days. The plaque index did not significantly change in either group over the study period. The trend of changes in plaque index was not different between the two groups of the study. In the current study, no side effect was found in the patients. Oral nano-curcumin has positive effects on the decrease of inflammation and gingival bleeding in patients with gingivitis and mild periodontitis. Nano-curcumin capsules have a systemic target site with more bioavailability than topical forms.

Topics: Capsules; Curcumin; Gingivitis; Humans; Inflammation; Periodontitis

The application of curcumin is limited by its instability. Mono-carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated.. The cytotoxicity of MCACs on MC3 T3-E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H. MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A-10A, 1H-10H), among which, 1A exhibited the most potent cytoprotective effect against H. The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis.

Topics: Animals; Antioxidants; Curcumin; Heme Oxygenase-1; NF-E2-Related Factor 2; Oxidative Stress; Periodontitis; Rats; Reactive Oxygen Species

There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats.. Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)-control group, (2) (DPP)-experimentally induced diabetes mellitus and periodontitis, (3) (DPC)-experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)-experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)-experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue.. The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin.. The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Curcumin; Diabetes Mellitus, Experimental; Hyperglycemia; Male; Oxidative Stress; Periodontitis; Rats; Rats, Wistar; Rutin

To evaluate the role of natural curcumin (CURC) on experimental periodontitis (EP) in animals with diabetes mellitus (DM).. One hundred rats were assigned to DM + placebo (PLA); DM + CURC; DM + insulin (INS); DM + CURC + INS; and Non-DM. Diabetes was induced by streptozotocin. After 3 days, they were initiated CURC and PLAC solutions and insulin administrations, daily for 30 days. This included a period of 19 days prior to EP induction (ligature at the first mandibular and the second maxillary molar) and then additional 11 days. Specimens from the mandible were processed for morphometric examination of bone level. Gingival tissues from mandibular molars were collected for quantification of IL-1β, IL-4, IL-6, IL-17, IFN-γ, and TNF-α using a Luminex/MAGpix assay. Gingivae from maxillary molars were subjected to RT-PCR for assessment of Runx2, RANKL, OPG, SIRT, Dkk1, and Sost levels.. Lower linear bone loss was detected in ligated molars of DM + CURC + INS vs DM + PLAC and DM + INS groups (P < 0.05). In ligated sites from DM rats treated with CURC + INS, IL-6, IL-1β, INF-γ, and TNF-α levels were the lowest in comparison with PLAC and/or INS and CURC as monotherapies (P < 0.05). CURC, independently of INS, increased Runx2 and SIRT when compared to DM + PLAC (P < 0.05) in ligated sites, whereas only CURC + INS reduced the RANKL/OPG ratio when compared to DM + PLAC (P < 0.05).. Natural CURC, when associated with INS, reduces the DM-induced loss of supporting alveolar bone and promotes favorable modulation on osteo-immune-inflammatory mediators.

Topics: Alveolar Bone Loss; Animals; Curcumin; Cytokines; Diabetes Mellitus, Experimental; Male; Periodontitis; Rats; Rats, Wistar; Streptozocin

Recently, antimicrobial photodynamic therapy (aPDT) as an alternative treatment modality has been used adjunctively in the treatment of periodontitis and peri-implantitis. Photosensitizing agents in the form of nanoparticles have been designed for improving the efficiency of aPTD. Graphene quantum dots are a special type of nanocrystals that can promote aPDT when coupled with curcumin (Cur). The main objective of the present study was to investigate the effects of photoexcited GQD-Cur on the metabolic activity of perio-pathogen mixed biofilms.. GQD-Cur was synthesized and characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible spectrometry (UV-Vis), and X-ray diffraction (XRD). The cell cytotoxicity effect of GQD-Cur was evaluated on primary human gingival fibroblast (HuGu) cells. Perio-pathogen mixed biofilms including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia photosensitized with GQD doped with Cur were irradiated with a blue LED at a wavelength of 435 ± 20 nm for 1 min, and then bacterial viability measurements were performed. The antimicrobial susceptibility profile, biofilm formation ability, amount of reactive oxygen species (ROS) released, and variations of gene expressions involved in biofilm formation were assessed.. The SEM, DLS, FTIR, UV-Vis spectrometry, and XRD pattern confirmed that GQD-Cur was synthesized successfully. According to the results, GQD-Cur exhibited no cytotoxicity against HuGu cells. Photoexcited GQD-Cur resulted in a significant reduction in cell viability (93%) and biofilm formation capacity (76%) of peri-pathogens compared to the control group (P < 0.05). According to the results, a significant concentration-dependent increase in the ROS generation was observed in perio-pathogens mixed cells treated with different doses of GQD-Cur-aPDT. Moreover, rcpA, fimA, and inpA gene expression profiles were downregulated by 8.1-, 9.6-, and 11.8-folds, respectively.. Based on the results, photoexcited GQD-Cur have a high potency of perio-pathogens suppression in planktonic and biofilm forms and downregulation of the biofilm genes expression pattern was exploited as a nanoscale-based platform for periodontitis.

Topics: Aggregatibacter actinomycetemcomitans; Biofilms; Cell Survival; Curcumin; Graphite; Peri-Implantitis; Periodontitis; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Prevotella intermedia; Quantum Dots; Reactive Oxygen Species

CMC2.24, a novel tri-ketonic chemically modified compound based on natural di-ketonic curcumin, has been shown to reduce bone loss and inflammatory mediators in experimental periodontitis, however, a potential dose-response relationship was not determined. The purpose of this study was to assess the effects of different doses of CMC2.24 on inflammation and bone resorption in vivo and also to describe on the effects of CMC2.24 on macrophage response.. CMC2.24 was administered daily to animals for 28 days by oral gavage, at the following doses: 0 (control), 1, 3, 10, and 30 mg/kg of body weight. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) into the gingival tissues. Outcomes assessed were bone resorption, detection of tartrate-resistant acid phosphatase, and determination of gene expression. In vitro, macrophages (RAW264.7) were treated with different concentrations of CMC2.24: 1, 3, 10, and 30 μM and then subjected to different activation stimuli. Gene expression, phagocytic activity, production of reactive oxygen species (ROS) and cytokine production were evaluated.. CMC2.24 inhibited bone resorption, osteoclastogenesis, and tumor necrosis factor (TNF)-α expression in vivo. These beneficial responses reached maximum levels at a dose of 1 mg/kg, i.e. no dose-dependent effect. In vitro, CMC2.24 reduced the production of TNF-α and interleukin-10, inhibited phagocytic activity and stimulated production of ROS. A dose-dependent effect was observed only for ROS production.. Low doses of CMC2.24 (1 mg/kg/day) administered orally were sufficient to significantly inhibit alveolar bone resorption associated with the experimental periodontal disease; whereas in vitro macrophage inflammatory gene expression and phagocytosis were reduced, whereas production of ROS was stimulated.

Topics: Alveolar Bone Loss; Animals; Curcumin; Gingiva; Inflammation; Lipopolysaccharides; Osteoclasts; Periodontitis; Tumor Necrosis Factor-alpha

Studies have documented the anti-inflammatory effects of spices, which may be related to treatment of chronic diseases. The purpose of this study was to evaluate the influence of curcumin and piperine and their association on experimental periodontal repair in rats.. Periodontitis was induced via the installation of a ligature around the first molar. After 15 days, the ligatures were removed, and the rats were separated into groups (12 animals per group): (i) curcumin, (ii) piperine, (iii) curcumin+piperine, (iv) corn oil vehicle, and (v) control group (animals had ligature-induced periodontitis but were not treated). The compounds were administered daily, for 15 days by oral gavage. Animals were euthanized at 5 and 15 days, and hemimaxillae and gingival tissues were harvested. Bone repair was assessed by μCT (microcomputer tomography). Histological sections were stained with hematoxylin/eosin (H/E) for the assessment of cellular infiltrate or picrosirius red for quantification of collagen content, and subjected to immunohistochemistry for detecting NF-ĸB. Gingival tissues were used to evaluate levels of TGF-β and IL-10 (ELISA).. Curcumin and piperine increased the TGF-β level, significantly improved the collagen repair, and decreased the cellularity and activation of NF-ĸB in the periodontal tissues, but only curcumin caused a significant increase in early bone repair.. Curcumin and piperine promoted a substantive effect on tissue repair; however, there was not synergistic effect of compounds administered in combination.. Curcumin and piperine stimulates the tissue repair and may be potential candidates for the treatment of periodontal disease.

Topics: Alkaloids; Animals; Benzodioxoles; Cats; Curcumin; Male; Periodontitis; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Wistar

The bystander effects, whereby naive (bystander) microbial cells near microbial cells directly exposed to certain treatment show responses that would not have happened in the absence of the directly targeted microbial cells, is recently documented in the field of microbiology. In this article, we discuss that substantial bystander responses are also observed after antimicrobial photodynamic therapy (aPDT) using curcumin (Cur).. Bystander effects induced by whole bacterial cell suspension (WBCS. A. actinomycetemcomitans cell survival reduced by 82.7% (P = 0.001) and 76.2% (P = 0.01) after exposure to WBCS. The results of the current study revealed that Cur-aPDT could significantly reduce microbial cell survival, cell metabolic activity, efflux capacity, and QS ability through the bystander effects. As a result, the bystander effects of Cur-aPDT along with the direct effect of Cur-aPDT can enhance the efficiency of aPDT as an adjunct therapeutic strategy for treatment of local infections.

Topics: Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Bystander Effect; Cell Survival; Curcumin; Microbial Viability; Peri-Implantitis; Periodontitis; Photochemotherapy; Photosensitizing Agents; Quorum Sensing

Periodontitis progresses due to increased levels of active metalloproteinases (MMPs) and the imbalance between MMPs and their tissue inhibitors (TIMPs). Natural curcumin limits the lytic activity of MMPs but has low cellular uptake. Use of synthetic curcumin analogs could be a means of overcoming this limitation of treatment efficiency. Human periodontal stem cells were isolated from gingival tissue, gingival ligament fibers, periodontal ligament, and alveolar bone. The effect of five synthetic curcumin analogs was compared with that of natural curcumin by assessing cytotoxicity [by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay], the cellular uptake (by fluorometry), the proteolytic activities of MMP-2 and -9 (by zymography), and the levels of TIMP-1 (by ELISA). Our results indicated increased cytotoxicity of synthetic curcumins for doses between 100 and 250 μM. At a concentration of 10 μM, cellular uptake of synthetic curcumins varied depending on their chemical structure. The curcumin compounds modulated pro-MMP-2 levels and increased TIMP-1 production. There was no detectable synthesis of pro-MMP-9 and no activation of MMPs 2 and 9. Gingival tissue and gingival ligament fiber stem cells were most responsive to treatment, showing inverse correlations between pro-MMP-2 and TIMP-1 levels. In conclusion, synthetic curcumins influenced the balance between pro-MMP-2 and TIMP-1 in human periodontal stem cells in vitro, and this could open perspectives for their application as adjuvants in periodontal therapy.

Topics: Cells, Cultured; Curcumin; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Periodontitis; Stem Cells; Tissue Inhibitor of Metalloproteinase-1

Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis.. Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis.. The film was developed by using solvent casting technique and "Design of Experiments" approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior.. Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04 ± 2.4, swelling index 138.10 ± 1.25, and folding endurance 270 ± 3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7 days.. The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.

Topics: Biodegradable Plastics; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Excipients; Gelatin; Humans; Periodontitis; Polymers

The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease.. Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.24 30 mg/kg body weight, (iii) Curcumin 100 mg/kg body weight and (iv) no treatment. Compounds were administered daily by oral intubation over a 15-day period of time. Periodontal disease was induced by injections of LPS (lipopolysaccharide) into the gingival tissues three times per week. Contralateral sides were injected with the same volume of PBS (phosphate buffered saline) vehicle. After 15 days, hemimaxillae and gingival tissues were harvested. Bone resorption was assessed by μCT (microcomputer tomography). Formalin-fixed, paraffin embedded histological sections were stained with haematoxylin/eosin (H/E) for the assessment of cellular infiltrate or subjected to immunohistochemistry for detecting TRAP (tartrate-resistant acid phosphatase)-positive cells and caspase-3. Apoptosis was assessed in the gingival tissues by DNA fragmentation.. CMC2.24 and curcumin caused a significant reduction of the inflammatory cell infiltrate, however μCT analysis showed that only CMC2.24 reduced bone resorption and the number of TRAP-positive multinucleated cells (osteoclasts). Curcumin, but not CMC2.24, significantly reduced the number of apoptotic cells in the gingival tissues and of osteocytes in the alveolar bone crest.. The results suggest that CMC2.24 and curcumin inhibit inflammation by different mechanisms, but only CMC2.24 was capable of reducing alveolar bone resorption in the LPS-induced model of periodontitis.

Topics: Administration, Oral; Alveolar Bone Loss; Animals; Apoptosis; Body Weight; Bone and Bones; Carboxymethylcellulose Sodium; Caspase 3; Curcumin; Disease Models, Animal; Gingiva; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Osteoclasts; Periodontitis; Rats; Tartrate-Resistant Acid Phosphatase; Time Factors; Tomography

Curcumin exhibits anti-inflammatory effects and has been suggested as a treatment for inflammatory diseases. The aim of this study was to investigate the effects of curcumin on the lipopolysaccharide induced inflammatory response in rat gingival fibroblasts in vitro and ligation-induced experimental periodontitis in vivo, and to speculate the possible anti-inflammatory mechanism of curcumin.. The gingival fibroblasts were incubated with different concentrations of curcumin in the absence or presence of lipopolysaccharide (LPS). Concentrations of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-B ligand (RANKL) culture supernatants of rat gingival fibroblasts were determined by enzyme linked immunosorbent assay. The nuclear fraction of rat gingival fibroblasts was extracted and nuclear factor kappa-B (NF-κB) activation was assessed by western blotting to elucidate related mechanisms. Curcumin was given every two days by oral gavage. The gingival inflammation and alveolar bone loss between the first and second molars were observed by hematoxylin and eosin staining. Collagen fibers were observed by picro-sirius red staining. Alveolar bone loss was assessed by micro-CT analysis.. Curcumin attenuated the production of IL-1β and TNF-α in rat gingival fibroblasts stimulated by LPS, and inhibited the LPS-induced decrease in OPG/sRANKL ratio and NF-κB activation. Curcumin significantly reduced gingival inflammation and modulated collagen fiber and alveolar bone loss in vivo.. curcumin modulates inflammatory activity in rat periodontitis by inhibiting NF-κB activation and decreasing the OPG/sRANKL ratio induced by LPS.

Topics: Animals; Cells, Cultured; Curcumin; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Gingiva; Interleukin-1beta; Male; Osteoprotegerin; Periodontitis; Random Allocation; Rats; Rats, Wistar; Reference Values; Sensitivity and Specificity; Tumor Necrosis Factor-alpha; X-Ray Microtomography

Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone.

Topics: Alveolar Bone Loss; Animals; Anti-Inflammatory Agents; Bone Remodeling; Curcuma; Disease Models, Animal; Gene Expression; Gingiva; Inflammation; Lipopolysaccharides; Male; Osteoblasts; Osteogenesis; Periodontitis; Phenols; Plant Extracts; Rats; Rats, Sprague-Dawley

The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC 2.24, or the vehicle, was administered by oral gavage daily for 3 weeks to the diabetics. Hemimaxillae and gingival tissues were harvested, and bone loss was assessed radiographically. Gingival tissues were pooled according to the experimental conditions and processed for the analysis of matrix metalloproteinases (MMPs) and bone-resorptive cytokines. Activation of p38 MAPK and NF-κB signaling pathways was assessed by western blot. Both LPS and diabetes induced an inflammatory process in the gingival tissues associated with excessive alveolar bone resorption and increased activation of p65 (NF-κB) and p38 MAPK. In both models, the administration of CMC 2.24 produced a marked reduction of inflammatory cytokines and MMPs in the gingival tissues, decreased bone loss, and decreased activation of p65 (NF-κB) and p38 MAPK. Inhibition of these cell signaling pathways by this novel tri-ketonic curcuminoid (natural curcumin is di-ketonic) may play a role in its therapeutic efficacy in locally and systemically associated periodontitis.

Topics: Alveolar Bone Loss; Animals; Curcumin; Cytokines; Diabetes Complications; Gingiva; Lipopolysaccharides; Matrix Metalloproteinases; Mitogen-Activated Protein Kinases; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Periodontal Diseases; Periodontitis; Rats

This study assessed the effect of curcumin as a photosensitizer in antimicrobial photodynamic therapy (aPDT) for the treatment of induced periodontitis in rats. Periodontitis was induced via a ligature around the mandibular first molar on the left side of 96 rats. The ligature was removed 7 days later, and the animals were randomized into four groups: NT, no local treatment; CUR, irrigation with curcumin solution (40 μM); LED, irradiation with a light-emitting diode (LED, InGaN, 465-485 nm, 200 mW/cm

Topics: Animals; Curcumin; Inflammation; Male; Mandible; Molar; Osteoprotegerin; Periodontitis; Photochemotherapy; Proliferating Cell Nuclear Antigen; RANK Ligand; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24.. Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA.. Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone.. This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction.

Topics: Alveolar Process; Animals; Anti-Inflammatory Agents; Connective Tissue; Curcumin; Diabetes Mellitus, Experimental; Disease Models, Animal; Gingiva; Inflammation; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Periodontitis; Rats; Rats, Sprague-Dawley; Skin

Periodontitis is a chronic inflammatory disease of periodontal tissues that leads to the destruction of bone and other connective tissues. Resveratrol and curcumin are plant-derived substances with biological properties that may have immunomodulatory properties. This study investigated the effect of continuous administration of resveratrol and curcumin and the association of resveratrol and curcumin on the progression of experimental periodontitis in rats.. Forty Wistar rats were assigned randomly to the following groups: group 1, experimental periodontitis + placebo (PL) (n = 10); group 2, experimental periodontitis + resveratrol (RSV) (n = 10); group 3, experimental periodontitis + curcumin (C) (n = 10); and group 4, experimental periodontitis + resveratrol + curcumin (COMBI) (n = 10). Periodontitis was induced in rats by tying a silk suture, as a ligature, around one of the first molars. Daily administration of the placebo solution, 10 mg/kg of resveratrol, 100 mg/kg of curcumin or 10 mg/kg of resveratrol plus 100 mg/kg of curcumin was carried out from day 0 to day 30. At the end of the relevant experimental periods, rats were killed and the specimens obtained were processed for morphometric analysis of bone loss. Gingival tissues surrounding the first molar were collected for quantification of interleukin (IL)-1β, IL-4, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) using a Luminex/MAGPIX assay.. Intergroup comparisons of the morphometric outcomes revealed higher bone-loss values in the PL group (p < 0.05) when compared with RSV, C and COMBI groups. There was no difference in bone-loss values among RSV, C and COMBI groups (p > 0.05). The immunoenzymatic assay of the gingival tissue showed a lower concentration of IL-1β in the COMBI group in comparison with the PL group (p < 0.05). Higher values of IL-4 were demonstrated in groups RSV, C and COMBI in comparison with the PL group (p < 0.05). Only RSV caused a reduction in the levels of IFN-γ (p < 0.05). There was no difference in the concentration of TNF-α amongst the four groups (p > 0.05).. Resveratrol and curcumin are capable of reducing alveolar bone loss in an animal model of periodontitis. This occurred when these agents were added singly or in combination with one another, but there did not appear to be either synergistic or additive effects.

Topics: Animals; Curcumin; Disease Models, Animal; Disease Progression; Drug Therapy, Combination; Gingiva; Immunologic Factors; Interferon-gamma; Interleukin-1beta; Male; Periodontitis; Rats; Rats, Wistar; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

This study aimed to develop syringeable in-situ curcumin (cur) gel for the treatment of periodontal pockets as well as to evaluate the clinical efficacy of Cur in-situ gel formulation. Different in-situ gel formulations of Cur were prepared using 30% of pluronic F127, and 1% of carbopol P934. The formulations were evaluated regarding gelation temperature, pH, viscosity, syringeability study, in-vitro release and chemical stability of cur. The effect of aging of gel formulations for 3months in refrigerator was investigated. The selected formulation was clinically evaluated through the determination of probing depth, plaque index, and bleeding index at baseline and 1 month after application. The formulations showed accepted gelation temperature ranging from 28 to 34 °C and all had pH value of 4. The viscosity of the formulations at 4 °C ranged from 19 000 to 37 000 cP. All formulations were easily syringeable through 21 gauge needle at cold temperature. Curcumin stability during the release study was maintained. Aging showed no significant effect on release profile, drug content, or the pH after 3 months, while it showed a slight increase in viscosity with concomitant decrease in gelation temperature. Selected formulations delivered into periodontal pocket evaluated clinically showed to be effective. The treated group revealed that the adjunctive use of intracrevicular 2% curcumin in-situ gel adjunct to mechanical treatment in patients with adult periodontitis could aid in significant clinical reduction of probing depth, bleeding index, and to less extent of plaque. This indicates that curcumin in this novel drug delivery system is an excellent candidate for periodontal disease treatment.

Topics: Adult; Chemistry, Pharmaceutical; Curcumin; Drug Delivery Systems; Female; Gels; Humans; Male; Middle Aged; Periodontitis; Poloxamer; Temperature; Viscosity

Curcumin has anti-inflammatory and antioxidant effects and is reported to have many biologic activities. The current study examines effect of curcumin on: 1) systemic T helper 17 (Th17) cell response; 2) gingival expressions of interleukin (IL)-17 and retinoic acid receptor-related orphan receptor (ROR) γt; and 3) alveolar bone loss (ABL) in experimental periodontitis.. Thirty-eight male albino Wistar rats were divided into four groups: 1) group 1 = periodontitis; 2) group 2 = periodontitis with curcumin treatment; 3) group 3 = periodontally healthy with curcumin treatment; and 4) group 4 = periodontally healthy. Curcumin was administered via oral gavage (30 mg/kg/d) for 15 days. After sacrifice via exsanguination, the following serum levels were determined using enzyme-linked immunosorbent assay: 1) IL-1β; 2) IL-6; 3) IL-17A; 4) IL-23; and 5) transforming growth factor- β. Morphometric evaluation of ABL was conducted and expression levels of IL-17 and RORγt in gingival tissues were evaluated immunohistochemically.. Group 2 had significantly lower ABL than group 1 (P <0.0125). Highest expression levels of IL-17 and RORγt were observed in group 1 and were significantly higher than those in all other groups (P <0.0125). The only serum biochemical parameter significantly different among groups was level of IL-23 (P <0.05). Serum IL-23 levels were higher in groups 1 and 2 than groups 3 and 4 (P <0.0125); however, they were not significantly different for groups 1 and 2 (P >0.0125).. Curcumin seems to be a promising host modulatory agent in periodontal disease pathogenesis regarding IL-17/IL-23 axis, with a decreasing effect on ABL and gingival expressions of IL-17 and RORγt.

Topics: Alveolar Bone Loss; Animals; Curcumin; Interleukin-17; Male; Nuclear Receptor Subfamily 1, Group F, Member 3; Periodontitis; Rats; Rats, Wistar; Receptors, Retinoic Acid

Periodontitis (PD) is a chronic infectious disease mediated by bacteria in the oral cavity. (Poly)phenols (PPs), ubiquitous in plant foods, possess antimicrobial activities and may be useful in the prevention and management of periodontitis. The objective of this study was to test the antibacterial effects of selected PPs on periodontal pathogens, on both planktonic and biofilm modes of growth. Selected PPs (n = 48) were screened against Streptococcus mitis (S. mitis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P. gingivalis). The antibacterial potential of each compound was evaluated in terms of planktonic minimum inhibitory concentration (PMIC) and planktonic minimum bactericidal concentration (PMBC) using standardized broth microdilution assays. The most active PPs were further tested for their effect on mono-species and multi-species biofilms using a colorimetric resazurin-based viability assay and scanning electron microscopy. Of the 48 PPs tested, 43 showed effective inhibition of planktonic growth of one or more test strains, of which curcumin was the most potent (PMIC range = 7.8-62.5 μg mL(-1)), followed by pyrogallol (PMIC range = 2.4-2500 μg mL(-1)), pyrocatechol (MIC range = 4.9-312.5 μg mL(-1)) and quercetin (PMIC range = 31.2-500 μg mL(-1)). At this concentration, adhesion of curcumin and quercetin to the substrate also inhibited adhesion of S. mitis, and biofilm formation and maturation. While both curcumin and quercetin were able to alter architecture of mature multi-species biofilms, only curcumin-treated biofilms displayed a significantly reduced metabolic activity. Overall, PPs possess antibacterial activities against periodontopathic bacteria in both planktonic and biofilm modes of growth. Further cellular and in vivo studies are necessary to confirm their beneficial activities and potential use in the prevention and or treatment of periodontal diseases.

Topics: Adsorption; Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Catechols; Curcumin; Durapatite; Fusobacterium nucleatum; Humans; Microbial Sensitivity Tests; Microbial Viability; Mouthwashes; Periodontitis; Polyphenols; Porphyromonas gingivalis; Pyrogallol; Quercetin; Streptococcus mitis; Structure-Activity Relationship

Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1β; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or μ-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations.

Topics: Animals; Curcumin; Lipopolysaccharides; Male; Matrix Metalloproteinase Inhibitors; Periodontal Diseases; Periodontitis; Rats

Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs). This ultimately results in the destruction of periodontal connective tissues including alveolar bone. Curcumin is the principal dyestuff in the popular Indian spice turmeric and has significant regulatory effects on inflammatory mediators but is characterized by poor solubility and low bioactivity. Recently, we developed a series of chemically modified curcumins (CMCs) with increased solubility and zinc-binding activity, while retaining, or further enhancing, their therapeutic effects. In the current study, we demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin) has significant inhibitory effects, better than the parent compound curcumin, on proinflammatory cytokines and MMPs in in vitro, in cell culture, and in an animal model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its congeners may help to prevent tissue damage during various chronic inflammatory diseases including periodontitis and may reduce the risks of systemic diseases associated with this local disorder.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Curcumin; Diabetes Mellitus, Experimental; Diarylheptanoids; Humans; Inflammation Mediators; Male; Matrix Metalloproteinase 9; NF-kappa B; Periodontitis; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Curcumin, an active ingredient of turmeric, is proved to be a potential candidate of controlling inflammation and bone resorption, but few reports are on the periodontitis. The purpose of this study was to evaluate whether the intra-gastric administration of curcumin could inhibit the inflammation and alveolar bone resorption in rats following ligature-induced experimental periodontitis.. Male Wistar rats were randomly divided into three groups: no ligature placement and administration of vehicle, ligature placement and administration of vehicle, ligature placement and administration of curcumin. After the animals were sacrificed, their mandibles were collected for morphological, histological and immunohistochemical analysis; their gingival tissues were collected for cytokine measurements.. Bone resorption was significantly higher in the experimental periodontitis animals treated with vehicle compared with the curcumin-treated group or the control group. Furthermore, receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels were higher in the experimental periodontitis animals treated with vehicle compared with the curcumin treated group or the control group. CONCLUSIONS. Curcumin may decrease alveolar bone loss in the experimental periodontitis rats via suppressing the expression of RANKL/RANK/OPG and its anti-inflammatory properties.

Topics: Animals; Curcumin; Immunohistochemistry; Inflammation; Inflammation Mediators; Male; Osteoporosis; Periodontitis; Rats; Rats, Wistar

Curcumin is a plant-derived dietary spice with various biological activities, including anticarcinogenic and anti-inflammatory effects. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression, but no studies have evaluated the effects of curcumin on periodontal disease in vivo.. Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats by the intragastric route daily at two dosages (30 and 100 mg/kg) for 15 d. Control animals received ligatures but only the corn oil vehicle by gavage, and no treatment-negative control animals were included. Bone resorption was assessed by micro-computed tomography, and the inflammatory status was evaluated by stereometric analysis. Both RT-qPCR and ELISA were used to determine the expression of interleukin-6, tumor necrosis factor-α and prostaglandin E(2) synthase in the gingival tissues. Modulation of p38 MAPK and nuclear factor-κB activation were assessed by western blotting.. Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at both the mRNA and the protein level and produced a dose-dependent inhibition of the activation of nuclear factor-κB in the gingival tissues. Activation of p38 MAPK was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction of the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers.. Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests that it may have a therapeutic potential in periodontal diseases.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Count; Collagen; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Fibroblasts; Gingiva; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Inflammation; Interleukin-6; Intramolecular Oxidoreductases; Male; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Periodontitis; Prostaglandin-E Synthases; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; X-Ray Microtomography

Porphyromonas gingivalis, a major periodontopathic bacterium, is necessary for periodontitis to take place. The lipopolysaccharide (LPS) of P. gingivalis stimulates cytokine secretion in immune cells, and thereby initiates the inflammation related to periodontitis. Macrophages are the important ones of the immune cells that are prominent at inflammatory periodontal sites. Curcumin, a major curcumanoid found in the spice turmeric, exhibits anti-inflammatory properties. The aim of this study was to investigate the anti-inflammatory effect and the mechanism of action of curcumin in macrophages stimulated by P. gingivalis LPS.. RAW264.7 cells pre-treated with various concentrations of curcumin were stimulated by P. gingivalis LPS. TNF-alpha and IL-1beta expressions were separately detected by RT-PCR and ELISA. Next, activation of NF-kappaB-dependent transcription was examined by luciferase assay.. Curcumin dose-dependently inhibited TNF-alpha and IL-1beta gene expression and protein synthesis in RAW264.7 cells stimulated with P. gingivalis LPS. P. gingivalis LPS activated NF-kappaB-dependent transcription in RAW264.7 cells, which were down-regulated by pre-treatment with curcumin as well.. Our data suggest that curcumin can inhibit P. gingivalis LPS-induced cytokine expression, and that this could be due to the inhibition of the NF-kappaB pathway.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Curcumin; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Inflammation; Interleukin-1beta; Lipopolysaccharides; Luciferases; Macrophages; Mice; NF-kappa B; Periodontitis; Porphyromonas gingivalis; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Tumor Necrosis Factor-alpha