Antimicrobial and antibiofilm activities of Brazilian organic honey against oral microorganisms.

OBJECTIVE: To evaluate the antimicrobial activity of Brazilian honeys against oral microorganisms. DESIGN: Organic honeys (OH-1 to OH-8) were diluted (%-w/v) and sterilized by filtration. Antimicrobial activity was defined by determining MIC and CBM against oral Streptococcus. The component responsible for the antimicrobial action was defined by a catalase assay. Antibiofilm activity was evaluated against the monospecies biofilm of Streptococcus mutans  (ATCC 700610). RESULTS: OHs showed antimicrobial activity principally OH-1, OH-2, OH-3, and OH-7 with MIC values ​​ranging between 10 and 25%. The mechanism of action occurs mainly by hydrogen peroxide produced by honey enzymes. OH-1, OH-2, and OH-7 showed total biofilm destruction at low concentrations. CONCLUSION: Brazilian honeys have promising antimicrobial and antibiofilm activity with the potential to control oral microbiota.

The synthetic antimicrobial peptide IKR18 displays anti-infectious properties in Galleria mellonella in vivo model.

Antimicrobial peptides (AMPs) are promising tools for developing new antibiotics. We described the design of IKR18, an AMP designed with the aid of computational tools. IKR18 showed antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). CD studies revealed that IKR18 assumes an alpha-helical structure in the membrane-mimetic environment. The action mechanism IKR18 involves damage to the bacteria membrane, as demonstrated by Sytox green uptake. Furthermore, IKR18 displayed synergic and additive effects in combination with antibiotics ciprofloxacin and vancomycin. The peptide showed anti-biofilm activity in concentration and efficiency compared with commercial antibiotics, involving the direct death of bacteria, as confirmed by scanning electron microscopy. The anti-infective activity of IKR18 was demonstrated in the Galleria mellonella model infected with S. aureus, MRSA, and Acinetobacter baumannii. The novel bioinspired peptide, IKR18, proved to be effective in the control of bacterial infection, opening opportunities for the development of further assays, including preclinical models.

A Study on the Anti-NF-κB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7.

INTRODUCTION: Gibberellins (GA) are terpenoids that serve as important plant hormones by acting as growth and response modulators against injuries and parasitism. In this study, we investigated the in vitro anti-NF-κB, anti-Candida, and antioxidant activity of gibberellin A4 (GA4) and A7 (GA7) compounds, and further determined their toxicity in vivo. METHODS: GA4 and GA7 in vitro toxicity was determined by MTT method, and nontoxic concentrations were then tested to evaluate the GA4 and GA7 anti-NF-κB activity in LPS-activated RAW-luc macrophage cell culture (luminescence assay). GA4 in silico anti-NF-κB activity was evaluated by molecular docking with the software "AutoDock Vina", "MGLTools", "Pymol", and "LigPlot+", based on data obtained from "The Uniprot database", "Protein Data Bank", and "PubChem database". The GA4 and GA7 in vitro anti-Candida effects against Candida albicans (MYA 2876) were determined (MIC and MFC). GA7 was also evaluated regarding the viability of C. albicans preformed biofilm (microplate assay). In vitro antioxidant activity of GA4 and GA7 was evaluated against peroxyl radicals, superoxide anions, hypochlorous acid, and reactive nitrogen species. GA4 and GA7 in vivo toxicity was determined on the invertebrate Galleria mellonella larvae model. RESULTS: Our data show that GA4 at 30 µM is nontoxic and capable of reducing 32% of the NF-κB activation on RAW-luc macrophages in vitro. In vitro results were confirmed via molecular docking assay (in silico), since GA4 presented binding affinity to NF-κB p65 and p50 subunits. GA7 did not present anti-NF-κB effects, but exhibited anti-Candida activity with low MIC (94 mM) and MFC (188 mM) values. GA7 also presented antibiofilm properties at 940 mM concentration. GA4 did not present anti-Candida effects. Moreover, GA4 and GA7 showed antioxidant activity against peroxyl radicals, but did not show scavenging activity against the other tested radicals. Both compounds did not affect the survival of G. mellonella larvae, even at extremely high doses (10 g/Kg). CONCLUSION: Our study provides preclinical evidence indicating that GA4 and GA7 have a favorable low toxicity profile. The study also points to GA4 and GA7 interference with the NF-κB via, anti-Candida activity, and a peroxyl radical scavenger, which we argue are relevant biological effects.

The Use of Essential Oils and Their Isolated Compounds for the Treatment of Oral Candidiasis: A Literature Review.

In this literature review, we present the main scientific findings on the antifungal activity of essential oils (EOs) applicable for a new drug formulation to treat oral candidiasis. Seven literature databases were systematically searched for eligible in vitro and clinical trials. Selected articles were screened for biological activity, botanical species, phytochemical composition, study design, and methodological quality. A total of 26 articles were included in the review, of which 21 were in vitro studies and 5 clinical trials. The most promising EOs were obtained from Allium tubeorosum, Cinnamomum cassia, Cinnamomum zeylanicum, and Coriandrum sativum L. Among the phytochemicals, citral and thymol were the most active. Clinical trials indicated that the EOs from Pelargonium graveolens and Zataria multiflora are potentially effective to treat oral candidiasis. Further nonclinical and clinical studies with these EO are warranted to determine their potential use and safety for the treatment of oral candidiasis.

Terpinen-4-ol and nystatin co-loaded precursor of liquid crystalline system for topical treatment of oral candidiasis.

This study was performed to develop a liquid crystalline system (LCS) incorporated with terpinen-4-ol and nystatin to evaluate its antifungal, antibiofilm, and synergistic/modulatory activity against Candida albicans. The LCS was composed of a dispersion containing 40% propoxylated and ethoxylated cetyl alcohol, 40% oleic acid, and 0.5% chitosan dispersion. According to analysis by polarized light microscopy, rheology, and mucoadhesion studies, the incorporation of 100% artificial saliva increased the pseudoplasticity, consistency index, viscosity, and mucoadhesion of the formulation. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity; the LCS containing terpinen-4-ol and nystatin effectively inhibited C. albicans growth at a lower concentration, displaying a synergistic action. Therefore, LCS incorporated with terpinen-4-ol and nystatin is a promising alternative for preventing and treating infections and shows potential for the development of therapeutic strategies against candidiasis.

Antimicrobial, anti-adherence and antibiofilm activity against Staphylococcus aureus of a 4-phenyl coumarin derivative isolated from Brazilian geopropolis.

The discovery of new drug candidates, especially from natural products, remains a promising approach to overcome the alarmingly high microbial resistance rates. A major 4-phenyl coumarin named cinnamoyloxy-mammeisin (CNM) isolated from stingless bee geopropolis showed interesting biological properties; however, its antimicrobial activity against Staphylococcus aureus has never been investigated. In order to clarify these properties, CNM isolated from geopropolis was initially tested against methicillin-susceptible and -resistant S. aureus strains. Further, the effects of CNM were assessed on the microbial adherence to human cells, biofilm formation and mature biofilm. Then, the acute toxicity of the compound was determined in Galleria mellonella. CNM showed bacteriostatic activity against methicillin-susceptible and -resistant S. aureus strains, with MIC of 11.3 µM. In addition, CNM at 5.7 µM reduced bacterial adherence to human keratinocytes from 1 to 3 h and disrupted biofilm formation by reducing cell viability and architecture, as evidenced by scanning electron microscopy. The acute toxicity assay indicated no significant harmful effects. Based on these findings, CNM can be considered a promising compound with anti-S. aureus properties and predicted low toxicity. Thus, it may be used as a drug candidate or lead compound for structure/activity optimization.

Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic options.

Candida auris emerged as a pathogen resistant to multiple antifungal and has been associated with nosocomial outbreaks with high transmission capacity between hospitalized individuals. C. auris was first described in 2009, after being isolated from the external ear canal discharge of a patient in Japan. The difficulty in identification, incorrect use of antifungal drugs, and treatment failure are causes of high mortality. Since then, C. auris has been increasingly reported from East Asia to North America, with substantial fatalities and misidentification. This review aims at describing the epidemiology, virulence, risk factors, resistance, and therapeutic options in C. auris infections.

Antimicrobial effect of photodynamic therapy using erythrosine/methylene blue combination on Streptococcus mutans biofilm.

BACKGROUND: Photodynamic therapy (PDT) has demonstrated promising results in the treatment of several clinical pathologies through the photochemical reaction caused by the combination of a photosensitizer and a light source. The objective of this study was to evaluate the antimicrobial effect of the combination of the photosensitizers (PSs) erythrosine/methylene blue activated by a white halogen light device on Streptococcus mutans biofilm. METHODS: Two separate experiments were conducted, the first using the PSs at the concentration of 100 µM, and the second 250 µM. The PSs were tested on S. mutans biofilms cultured for 24 h in isolation, in combination, with and without light activation for 2 min fractionated in 4 periods of 30 s. After treatment, biofilms were diluted and plated on BHI medium and incubated for 24 h for colony forming units (CFU) counting. The results (log10) were analyzed with ANOVA followed by Tukey test (p < 0.05). RESULTS: The erythrosine/methylene blue combination activated by white halogen light at 100 and 250 µM, and erythrosine at 250 µM, methylene blue at 250 µM presented significantly reduced cell counts (3.2 log10, 5.3 log10, 4.5 log10, 4.3 log10, respectively) when compared to controls (p < 0.05). CONCLUSION: PDT with the combination of erythrosine/methylene blue demonstrated better results that the PSs in isolation regardless of the concentration. The use of this combination at the concentration of 250 µM shows promise as an antibacterial treatment for carious lesions and should be further assessed.

The alveolar bone protective effects of natural products: A systematic review.

OBJECTIVES: This systematic review was carried out to identify which naturally-occurring agents and constituents isolated therefrom have effects in preventing bone loss in a ligature-induced periodontitis model. MATERIALS AND METHODS: Eight databases were systematically searched for studies of experimental periodontitis. The data were extracted, analyzed, and the treatment outcomes were given scores based on the level of bone destruction as compared to their untreated induced-periodontitis control. RESULTS: 294 articles were found, of which 15 met the inclusion criteria. The selected studies tested a multi-herbal formulation; extracts (leaves, barks or fruit) of different plant species; and propolis. The most usual dosing protocol consisted of 3-times-a-day, 11-day treatment. The combined gel of Myracrodruon urundeuva (5%) and Lippia sidoides (0.5%) was the most active treatment, reducing 45-65% bone loss in the region of molars as compared to 73.4% of doxycycline (gold-standard). Ginkgo biloba extract (28-56 mg/kg) and propolis (100-200 mg/kg) prevented bone destruction by 50% and 40-44%, respectively. The other tested samples showed intermediate/weak activity in modulating bone resorption. CONCLUSIONS: The gel of M. urundeuva and L. sidoides, and G. biloba and propolis extracts showed strong alveolar bone protective effectiveness in induced-periodontitis in rats. Further translational research should bridge the gap between the rat study outcomes and the clinical efficacy and long-term toxicity of these formulations in humans. The compilation of the vast literature database presented herein may drive further in vivo and clinical studies with the selected efficacious formulations to subsidize their pharmaceutical application.

Anti dermatophytic therapy--prospects for the discovery of new drugs from natural products.

Millions of people and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which only infect keratinized structures. With the appearance of AIDS, the incidence of dermatophytosis has increased. Current drug therapy used for these infections is often toxic, long-term, and expensive and has limited effectiveness; therefore, the discovery of new anti dermatophytic compounds is a necessity. Natural products have been the most productive source for new drug development. This paper provides a brief review of the current literature regarding the presence of dermatophytes in immunocompromised patients, drug resistance to conventional treatments and new anti dermatophytic treatments.

Conventional and alternative antifungal therapies to oral candidiasis.

Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis.

Clinical and laboratory evaluations of non-surgical periodontal treatment in subjects with diabetes mellitus.

BACKGROUND: The aim of this study was to evaluate the clinical and laboratory changes 3 months after full-mouth scaling and root planing in subjects with and without diabetes mellitus. METHODS: This study was performed using 10 subjects with type 2 diabetes mellitus who required insulin therapy (DM) and 10 healthy adult control subjects (NDM) with generalized chronic periodontal disease. Both groups were treated with full-mouth scaling and root planing and given oral hygiene instructions. Clinical parameters, including plaque index (PI), gingival index (GI), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL), were measured at four sites per tooth. Subgingival plaque samples were obtained from sites with the deepest PD (> or =5 mm) and with furcations in each subject. Samples were also tested for the presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T. forsythensis) by polymerase chain reaction. Glycemic control (glycosylated hemoglobin [HbA1c] and fasting glucose levels) and clinical and microbiologic assessments were recorded at baseline and 3 months after periodontal treatment. RESULTS: Data revealed statistical changes (P < or =0.05; analysis of variance [ANOVA]) in clinical variables (PI, GI, PD, GR, and CAL) between baseline and 3 months in both groups. Conversely, no improvement in the fasting glucose level or glycosylated hemoglobin (P < or =0.05; ANOVA) was found after treatment. Besides some reduction in the bacterial frequency 3 months after treatment, no statistically significant difference was found between the groups. CONCLUSION: Clinical and laboratory responses were similar in DM and NDM groups 3 months after full-mouth scaling and root planing.