Assessing the efficacy of gutiferone E in photodynamic therapy for oral candidiasis.

The rise in antifungal resistance and side effects of conventional treatments drive the search for innovative therapies like Photodynamic Therapy (PDT). This study explored the efficacy of PDT mediated by gutiferone, an isolated compound from red propolis, for candidiasis treatment. Multiple evaluation methods were employed, including determining the minimum inhibitory concentration (MIC) via broth microdilution, quantifying biomass using crystal violet detachment, and cell counting through total plate count. PDT mediated by gutiferone was also assessed in five groups of mice, followed by histopathological examination and agar plating of lingual tissue samples. Among the seven Candida species tested, gutiferone displayed efficacy against C. albicans, C. glabrata, and C. tropicalis, with MIC values of 1000 µg/mL. In C. tropicalis biofilms, exposure to gutiferone led to a reduction of 1.61 Log10 CFU/mL. PDT mediated by gutiferone achieved an average reduction of 3.68 Log10 CFU/mL in C. tropicalis biofilm cells, underscoring its potent fungicidal activity. Histopathological analysis revealed fungal structures, such as pseudohyphae and hyphae, in infected groups (G2) and irradiated mice. In contrast, groups treated with gutiferone or subjected to gutiferone-assisted PDT (G5) exhibited only few blastoconidia. Furthermore, CFU/mL assessments in lingual tissue post-treatment demonstrated a significantly lower count (0.30 Log10 CFU/mL) in the G5 group compared to G2 (2.43 Log10 CFU/mL). These findings highlight the potential of PDT mediated by gutiferone as a promising alternative for managing denture stomatitis. Future research and clinical investigations offer the promise of validating its clinical applicability and improving outcomes in the treatment of oral candidiasis.

Curcuminoid-Mediated Antimicrobial Photodynamic Therapy on a Murine Model of Oral Candidiasis.

Antimicrobial Photodynamic Therapy (aPDT) has been extensively investigated in vitro, and preclinical animal models of infections are suitable for evaluating alternative treatments prior to clinical trials. This study describes the efficacy of aPDT in a murine model of oral candidiasis. Forty mice were immunosuppressed with subcutaneous injections of prednisolone, and their tongues were inoculated using an oral swab previously soaked in a C. albicans cell suspension. Tetracycline was administered via drinking water during the course of the experiment. Five days after fungal inoculation, mice were randomly distributed into eight groups; a ninth group of untreated uninfected mice was included as a negative control (n = 5). Three concentrations (20 µM, 40 µM, and 80 µM) of a mixture of curcuminoids were tested with a blue LED light (89.2 mW/cm2; ~455 nm) and without light (C+L+ and C+L- groups, respectively). Light alone (C-L+), no treatment (C-L-), and animals without infection were evaluated as controls. Data were analyzed using Welch's ANOVA and Games-Howell tests (α = 0.05). Oral candidiasis was established in all infected animals and visualized macroscopically through the presence of characteristic white patches or pseudomembranes on the dorsum of the tongues. Histopathological sections confirmed a large presence of yeast and filaments limited to the keratinized layer of the epithelium in the C-L- group, and the presence of fungal cells was visually decreased in the images obtained from mice subjected to aPDT with either 40 µM or 80 µM curcuminoids. aPDT mediated by 80 µM curcuminoids promoted a 2.47 log10 reduction in colony counts in comparison to those in the C-L- group (p = 0.008). All other groups showed no statistically significant reduction in the number of colonies, including photosensitizer (C+L-) or light alone (C-L+) groups. Curcuminoid-mediated aPDT reduced the fungal load from the tongues of mice.

[New opportunities for complex treatment of oropharyngeal candidiasis in HIV-infected patients in the later stages of the disease].

Treatment of recurrent oropharyngeal candidiasis (OPC) in HIV-infected patients is a serious clinical problem due to the emergence of resistant Candida strains, the risk of invasive disease, and high economic costs, which warrants the need for new treatment regimens. AIM: To improve the treatment regimen of OPC in the later stages of HIV infection by combining the complex herbal medicinal product Tonsilgon® N with fluconazole and evaluate the effectiveness of this combination. MATERIALS AND METHODS: A comparative randomized clinical study included 65 patients divided into observation and comparison groups, receiving fluconazole plus Tonsilgon® H and fluconazole monotherapy, respectively, for 7 days. On days 1 and 8, the severity of OPC clinical signs was assessed using a visual analog scale. The secretory immunoglobulin A in saliva was measured as a criterion for changing the level of local mucosal protection of the oral cavity and pharynx. CONCLUSION: This treatment regimen for oropharyngeal candidiasis in patients with HIV infection in the later stages of the disease (IVB-IVC) with fluconazole and Tonsilgon® N is effective, which is confirmed by a significantly more pronounced regression of clinical signs (pM-U<0.01), as well as an increase in the level of secretory immunoglobulin A in the oral fluid (from 0.62±0.33 g/L to 0.81±0.18 g/L; p<0.05).

Oral Candidiasis and Novel Therapeutic Strategies: Antifungals, Phytotherapy, Probiotics, and Photodynamic Therapy.

Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans, normally a saprophyte of the oral cavity, may become virulent and infect the oral mucosa with variegated clinical presentation, in case of imbalance of the oral microbiota, the presence of local predisposing factors and systemic conditions that weaken the immune system. Conventionally, oral candidiasis eradication is done with the help of antifungal drugs. However, the growing phenomena of drug resistance and the increase in infections sustained by non-albicans species being less responsive to common antifungals have orientied researches towards the experimentation of alternative therapies. The present review considered the most promising alternative therapeutic proposals. The use of plant derivatives with phytotherapy is a promising option, such as probiotics, to rebalance the oral microbiota in case of dysbiosis. Finally, antimicrobial photodynamic therapy (aPDT), with highly selective fungicidal activity and free of side effects, is also being studied as a powerful alternative to drug administration. All these therapies are alternatives or supportive to the conventional treatment of recurrent and non-drug-responsive forms of oral candidiasis. However, further studies are needed to define the most active compounds, the efficacy of the therapies compared with the conventional ones, and the planning of regulated and standardized protocols.

Curcumin nanoparticles: the topical antimycotic suspension treating oral candidiasis.

Phytotherapeutics is widely used nowadays as an alternative to the current antifungal drugs to reduce their side effects. Curcumin, with its wide therapeutic array as antioxidant and anti-inflammatory agent, is one of the natural compounds that ha..s an antifungal effect, especially when being used at nanoscale to increase its bioavailability. Our research aimed to evaluate clinically and microbiologically the effect of using topical nanocurcumin suspension to treat oral candidiasis. After 4 days from induction of oral candidiasis (baseline), we randomly divided 39 female BALB/c mice into three groups of 13 animals; nanocurcumin, nystatin, and sham groups. All animals in nanocurcumin and nystatin groups received topical treatment twice daily for 10 days. Then, we performed clinical and microbiological evaluations at baseline, day 5, and day 10. By the end of treatment, our results revealed that nanocurcumin promoted a significant reduction in the number of candida colonies. There was no statistically significant difference neither clinically nor microbiologically between nanocurcumin and nystatin groups. In conclusion, nanocurcumin has a good antifungal effect as nystatin, however, its therapeutic efficacy takes a longer time to appear than nystatin. The enhanced bioavailability of curcumin at the nanoscale qualifies this nano-herb as a promising alternative therapy for oral candidiasis, evading nystatin-associated morbidity.

Management of Denture Infection with Phytomedicine.

Natural teeth are an integral part of the masticatory system. Absence of dentition subjects the individual to compromised oral function, facial appearance and phonetics. Rehabilitation with dental prosthesis is imperative to restore form and masticatory activity. Currently, fabrication of removable and fixed prosthesis has become most predictable. Nonetheless, there is an increased prevalence of oral stomatitis observed over the years in edentulous individuals wearing removable dentures. Amongst the many pathogens that cause denture infections, Candida albicans is assumed to be the most virulent opportunistic agent. Different methods, such as mechanical, chemical, chemicmechanical, and pharmacological are tried to fight such infections. Regardless of various management strategies developed to treat denture stomatitis, the research continues to evolve the most optimal one. Improper oral and or denture hygiene maintenance, surface irregularities on denture, persistence of xerostomia and associated systemic illness pose risk for exaggeration of the disease. In extreme conditions, the development of aspiration pneumonia in geriatric patients is considered a threat to both dental and medical specialists. Therapeutic administration of synthetic anti-microbial drugs, along with meticulous oral hygiene maintenance are recommended protocols till date. However, limitations such as antibiotic resistance, side effects, counter drug reactions, cost of the medicaments predispose to origin of natural herbal products to treat denture stomatitis. Vast array of plant products are studied in previous literature, yet no definitive edge of one over the other is proven. This article intends to provide a mini-review on the different organic plant materials, also called as phytomedicines used for the treatment of candida associated denture stomatitis (CADS).

Photodynamic therapy in the treatment of denture stomatitis: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Photodynamic therapy is widely used in dentistry, but limited evidence exists regarding its effectiveness in treating denture stomatitis. High resistance to antifungals has been reported, and photodynamic therapy could be an alternative treatment. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether photodynamic therapy is effective in reducing denture stomatitis. MATERIAL AND METHODS: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and recorded in the prospective register of systematic reviews (PROSPERO) (CRD42020205589) to answer the population, intervention, control, outcome (PICO) question: "Is photodynamic therapy effective in the treatment of denture stomatitis when compared with the use of antifungal agents?" Electronic searches were performed in databases PubMed/MEDLINE, Cochrane library, and Web of Science for articles published until February 2021 by using the following terms: (denture stomatitis OR oral candidiasis) AND (low-level light therapy OR laser therapy OR lasers OR photodynamic therapies OR photochemotherapy) AND (antifungal drugs OR antifungal agents OR antimicrobial OR treatment). Clinical trials and randomized clinical trials, studies in the English language, and studies comparing antifungal agents with photodynamic therapy were included. RESULTS: In total, 5 articles were selected for the qualitative analysis and 3 for the meta-analysis. No significant difference was detected between antifungal therapy and photodynamic therapy in the reduction of colony-forming units on the palate. In a subgroup analysis, a significant difference was found in the reduction of colony-forming units on the palate at 15 days and at the denture surface at 30 days. CONCLUSIONS: Photodynamic therapy is effective in the treatment of denture stomatitis, but after 30 days and 15 days, the antifungals demonstrated better performance.

Therapeutic Effect of Green Synthesized Silver Nanoparticles Using Erodium glaucophyllum Extract against Oral Candidiasis: In Vitro and In Vivo Study.

Oral candidiasis (OC) is a fungal infection caused by an opportunistic fungi Candida albicans, which is found in the normal flora of healthy people. In this study, we examined the anti-candidal effect of green synthesized silver nanoparticles using leaf extract of Erodium glaucophyllum (EG-AgNPs) against C. albicans in vitro and in vivo. EG-AgNPs were synthesized for the first time using E. glaucophyllum extract and characterized by imaging (transmission electron microscopy (TEM), UV-VIS spectroscopy, zeta potential, X-ray diffraction (XRD), Energy dispersive x-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR). A mouse model of OC was used for in vivo study. The agar well diffusion method showed the anti-candidal activity of EG-AgNPs against C. albicans with MIC 50 µg/mL. EG-AgNPs inhibited the dimorphic transition of C. albicans and suppressed the formation of biofilm by 56.36% and 52%, respectively. Additionally, EG-AgNPs significantly inhibited the production of phospholipases and proteinases by 30% and 45%, respectively. EG-AgNPs cause cytoplasm disintegration and deterioration of cell wall as imaged by SEM and TEM. Interestingly, EG-AgNPs did not display any cytotoxicity on the human gingival fibroblast-1 HGF-1 cell line at MIC concentrations. Topical treatment of the tongue of the OC mouse model with EG-AgNPs showed significant reduction in candidal tissue invasion, less inflammatory changes, and no tissue modification, in association with marked low scare and hyphal counts as compared to control group. In conclusion, our data demonstrated the potent inhibitory action of EG-AgNPs on the growth and morphogenesis of C. albicans in vitro and in vivo. Thus, EG-AgNPs represent a novel plausible therapeutic approach for treatment of OC.

Comparison between two antimicrobial photodynamic therapy protocols for oral candidiasis in patients undergoing treatment for head and neck cancer: A two-arm, single-blind clinical trial.

Purpose This study aimed to compare the efficacy of Antimicrobial Photodynamic Therapy (aPDT) with 300 µmol/L of methylene blue and 8 µmol/L of curcumin on oral candidiasis patients with HNSCC undergoing treatment. Methods A two-arm, single-blind clinical trial was performed. Following verification for eligibility (n = 447), 108 patients were included in the study. The study consisted of a group that received aPDT with methylene blue (n = 57) and another that received aPDT with curcumin (n = 51). The patients rinsed their mouths with an aqueous solution of 300 µmol/L of methylene blue and 8 µmol/L of curcumin in four sessions, and then the lesion was scraped for the subsequent RT-qPCR. The primary outcome was that no cure was presented for oral candidiasis after treatment. The secondary result was reducing the number of sites affected by oral candidiasis. Results There was no difference in treatment failure evaluated by the necessity of drug prescription or Candida sp DNA quantification. However, clinically the methylene blue protocol reduced the number of infected anatomical sites compared to the curcumin protocol. Conclusion Methylene blue aPDT reduced the number of infected anatomical sites compared to curcumin.

Combination treatment with photodynamic therapy and laser therapy in chronic hyperplastic candidiasis: A case report.

Chronic hyperplastic candidiasis (CHC) is a rare subtype of oral candidiasis. Due to the malignant transformation potential of this disease, its treatment deserves attention. Here we report a refractory case of an 85-year-old female with chronic hyperplastic candidiasis treated with combined photodynamic therapy and laser therapy with a superior clinical result. The patient had a two-months history of thick white plaque on her upper inner lip. Conventional antifungal therapy and repeated photodynamic therapy contributed slightly improvement to the hyperkeratosis lesion, and then it was removed by laser therapy. Recurrence was found at the follow-up visit of eighth- week, and the recurrent lesion was removed again by laser therapy and prophylactic photodynamic therapy was performed. The patient is still under follow-up.

Sodium houttuyfonate enhances the mono-therapy of fluconazole on oropharyngeal candidiasis (OPC) through HIF-1α/IL-17 axis by inhibiting cAMP mediated filamentation in Candida albicans-Candida glabrata dual biofilms.

Candida albicans and Candida glabrata are two common opportunistic fungi that can be co-isolated in oropharyngeal candidiasis (OPC). Hypha is a hallmark of the biofilm formation of C. albicans, indispensable for the attachment of C. glabrata, which is seldom in mycelial morphology. Increasing evidence reveals a hypoxic microenvironment in interior fungal biofilms, reminding of a fact that inflammation is usually accompanied by oxygen deprivation. As a result, it is assumed that the disaggregation of hypha-mediated hypoxia of biofilms might be a solution to alleviate OPC. Based on this hypothesis, sodium houttuyfonate (SH), a well-identified traditional herbal compound with antifungal activity, is used in combination with fluconazole (FLU), a well-informed synthesized antimycotics, to investigate their impact on filamentation in C. albicans and C. glabrata dual biofilms and the underlying mechanism of their combined treatment on OPC. The results show that compared with the single therapy, SH plus FLU can inhibit the hyphal growth in the mixed biofilms in vitro, decrease the fungal burden of oral tissues and internal organs, restore mucosal epithelial integrity and function, and reduce hypoxic microenvironment and inflammation in a mice OPC model. The possible mechanism of the combined therapy of SH plus FLU can be attributed to the regulation of HIF-1α/IL-17A axis through direct abrogation of the dual Candida biofilm formation. This study highlights the role of HIF-1α/IL-17A axis and the promising application of SH as a sensitizer of conventional antifungals in the treatment of OPC.

Paeonol enhances treatment of fluconazole and amphotericin B against oropharyngeal candidiasis through HIF-1α related IL-17 signaling.

Oropharyngeal candidiasis (OPC) is an oral infection mainly caused by Candida albicans, a dimorphic human opportunistic pathogen that can proliferate and invade the superficial oral epithelium using its hyphae. The filamentation of C. albicans is a hallmark of biofilm formation, accompanied by the occurrence of a hypoxic microenvironment. Paeonol (PAE) is a traditional medicine with multiple properties. In a previous study, we demonstrated the synergism of PAE plus Fluconazole (FLU) or Amphotericin B (AmB) against C. albicans in vitro and in vivo. This study aimed to explore the therapeutic mechanisms of drug combinations on OPC. In an established OPC mouse model, the culture of hypoxia was observed by calcofluor white and hypoxyprobe staining. The expression and levels of IL-17 signaling-associated genes and proteins (IL-17A and IL-23) were evaluated in tissue homogenates and EC109 cells. The results show that compared with the single therapy, PAE plus FLU or AmB can decrease fungal burden, restore mucosal integrity, and reduce the hypoxic microenvironment and inflammation in the OPC mice. Relative to infected mice, the drug combinations can also rectify the abnormal expression of hypoxia inducible factor (hif)-1α, il-17a, and il-23 mRNA. Meanwhile, compared with the infected EC109 cells treated with a single drug, PAE plus FLU or AmB significantly inhibited the mRNA and protein expression of HIF-1α, IL-17A, and IL-23. Taken together, the possible mechanism of PAE plus FLU or AmB can be attributed to the regulation of hypoxia-associated IL-17 signaling in OPC treatment.

Development, optimization, and evaluation of a nanostructured lipid carrier of sesame oil loaded with miconazole for the treatment of oral candidiasis.

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p < .05) higher for MZ-SO NLC (1472 µg/cm2) as compared with a marketed MZ formulation (1215 µg/cm2) and an aqueous MZ suspension (470 µg/cm2). Additionally, an in vivo efficacy study in terms of the ulcer index against C. albicans found a superior result for the optimized MZ-SO NLC (0.5 ± 0.50) in a treated group of animals. Hence, it can be concluded that MZ, through an optimized NLC of SO, can treat candidiasis effectively by inhibiting the growth of C. albicans.

Synergistic effect of thymoquinone and nystatin in the treatment of oral candidiasis; an in vitro study.

The effectiveness of antifungal agents may be insufficient against resistant strains in some cases of oral candidiasis. The aim of this study was to evaluate the antifungal effect of thymoquinone against Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei strains and the synergistic antifungal activity of these strains in combination with nystatin. To evaluate in vitro antifungal activity and interactions between thymoquinone and nystatin, substances were tested against Candida albicans ATCC 10,231, C. tropicalis ATCC 750, C.krusei ATCC 6258 and C. glabrata ATCC 2001 standard strains both individually and combinationally via microdilution method. MIC and ΣFIC index value were analysed. The Kruskal Wallis test and Bonferroni test were used for statistical evaluations. Statistical significance was set at p < 0.05. A statistically significant difference was observed between the mean ranks of all Candida species and doses of thymoquinone, nystatin, and the combination thymoquinone-nystatin (p < 0.05). MIC values for thymoquinone were determined as 15 µg/mL for C. albicans, C. tropicalis and C. krusei while it was 30 µg/mL for C. glabrata. Moreover, MIC for nystatin was found as 1.875 µg/mL for C. albicans, C. tropicalis and C. krusei, whereas it was 7.5 µg/mL in C. glabrata. Interaction assays and ΣFIC index value revealed that, TQ and nystatin have a synergistic effect against to all strains. Thymoquinone was found to have antifungal activity on Candida species and synergistic effect when combined with nystatin.

Activity of antifungal drugs and Brazilian red and green propolis extracted with different methodologies against oral isolates of Candida spp.

BACKGROUND: Oral candidiasis is an opportunistic disease caused by fungi of the Candida genus. The occurrence of Candida spp. resistance to the commercial antifungal drugs points to the search for alternative treatments. Propolis has been successfully used in the treatment of infectious diseases for centuries. It has been proposed that an ultrasound pretreatment in the propolis extraction protocol can enhance the concentrations of molecules with antimicrobial activities in the final extract. Thus, this study aimed to compare the antifungal activity against oral Candida spp. isolates of green and red propolis extracts submitted or not to an ultrasound pretreatment before the extraction procedure. METHODS: Candida spp. were isolated from denture stomatitis lesions and identified by sequencing. Oral Candida spp. isolates and reference strains were submitted to broth microdilution assays using commercial antifungals and Brazilian green and red propolis extracts submitted or not to an ultrasound pretreatment. Minimal Inhibitory Concentrations (MIC) and Minimal Fungicide Concentrations (MFC) were determined and biofilm formation interference was evaluated for resistant isolates. RESULTS: C. albicans, Candida tropicalis and Candida dubliniensis were isolated from denture stomatitis lesions. Growth inhibition was observed in all Candida isolates incubated with all green and red propolis extracts. At lower doses, red propolis extracts presented significant antifungal activity. The ultrasound pretreatment did not promote an increase in the antifungal activity of green or red propolis. Three isolates, which were highly resistant to fluconazole and itraconazole, were susceptible to low doses of red propolis extracts. These same three specimens had their biofilm formation inhibted by red propolis ethanolic extract. CONCLUSIONS: Thus, red propolis can be faced as a promising natural product to be used in the auxiliary antifungal therapy of denture stomatitis.

Artemisinin elevates ergosterol levels of Candida albicans to synergise with amphotericin B against oral candidiasis.

Oral candidiasis, especially caused by Candida albicans, is the most common fungal infection of the oral cavity. The increase in drug resistance and lack of new antifungal agents call for new strategies of antifungal treatment. This study repurposed artemisinin (Art) as a potentiator to the polyene amphotericin B (AmB) and characterised their synergistic mechanism against C. albicans and oral candidiasis. The synergistic antifungal activity between Art and AmB was identified by the checkerboard and recovery plate assays according to the fractional inhibitory concentration index (FICI). Art showed no antifungal activity even at >200 mg/L. However, it significantly reduced AmB dosages against the wild-type strain and 75 clinical isolates of C. albicans (FICI ≤ 0.5). Art significantly upregulated expression of genes from the ergosterol biosynthesis pathway (ERG1, ERG3, ERG9 and ERG11), as shown by RT-qPCR, and elevated the ergosterol content of Candida cells. Increased ergosterol content significantly enhanced binding between fungal cells and the polyene agent, resulting in sensitisation of C. albicans to AmB. Drug combinations of Art and AmB showed synergistic activity against oral mucosal infection in vivo by reducing the epithelial infection area, fungal burden and inflammatory infiltrates in murine oropharyngeal candidiasis. These findings indicate a novel synergistic antifungal drug combination and a new Art mechanism of action, suggesting that drug repurposing is a clinically practical means of antifungal drug development and treatment of oral candidiasis.

The Effects of Nutraceuticals and Herbal Medicine on Candida albicans in Oral Candidiasis: A Comprehensive Review.

Candida albicans is part of the healthy flora in the oral cavity. It can also cause opportunistic infection, which can be deleterious. The most typical type of chronic oral candidiasis is denture stomatitis, and C. albicans is identified as the most crucial organism in this situation. Due to the development of the resistant form of candida, using conventional drugs can sometimes be ineffective. Herbs and naturally imitative bioactive compounds could become a new source for antimycotic therapy. Several review studies suggest that herbal medicine and natural bioactive compounds have antibacterial, antiviral and antifungal effects. Thus, it is hypothesized that these natural products might have beneficial effects on pathogenic oral fungal flora such as C. albicans. Although the effects of herbs have been investigated as antifungal agents in several studies, to the best of our knowledge, the effects of these natural products on C. albicans have not yet been reviewed. Thus, the aim of this study was to review the anti-candida activity (especially C. albicans in oral candidiasis) of herbal medicines and natural bioactive compounds. It is concluded that, in general, medicinal plants and nutraceuticals such as garlic, green tea, propolis, curcumin, licorice root, cinnamon, resveratrol, ginger, and berberine are useful in the treatment of C. albicans in oral candidiasis and could be considered as a safe, accessible, and inexpensive management option in an attempt to prevent and treat oral diseases. However, most of the evidence is based on the in vitro and animal studies, so more clinical trials are needed.

Ellagic Acid-Cyclodextrin Complexes for the Treatment of Oral Candidiasis.

The increase in the prevalence of fungal infections worldwide and the rise in the occurrence of antifungal resistance suggest that new research to discover antifungal molecules is needed. The aim of this study was to evaluate the potential use of ellagic acid-cyclodextrin complexes (EA/HP-ß-CD) for the treatment of oral candidiasis. First, the effect of EA/HP-ß-CD on C. albicans planktonic cells and biofilms was evaluated. Then, the cytotoxicity of the effective concentration was studied to ensure safety of in vivo testing. Finally, the in vivo effectiveness was determined by using a murine model of induced oral candidiasis. Data was statistically analyzed. The minimal inhibitory concentration of EA/HP-ß-CD was 25 µg/mL and a concentration of 10 times MIC (250 µg/mL) showed an inhibitory effect on C. albicans 48 h-biofilms. The complex at concentration 250 µg/mL was classified as slightly cytotoxic. In vivo experiments showed a reduction in fungal epithelial invasion after treatment with EA/HP-ß-CD for 24 h and 96 h when compared to the negative control. In conclusion, the results demonstrated that EA/HP-ß-CD has antifungal and anti-inflammatory effects, reducing the invasive capacity of C. albicans, which suggests that EA/HP-ß-CD may be a promising alternative for the treatment of oral candidiasis.

Efficacy of essential oil of cinnamon for the treatment of oral candidiasis: A randomized trial.

AIM: It was analyzed the efficacy of mouthwash and spray containing essential oil (EO) of Cinnamomum zeylanicum Blume for the treatment of oral candidiasis. METHODS AND RESULTS: A randomized, controlled, and blinded clinical trial was conducted with 36 individuals (probabilistic sample) with oral candidiasis who were divided into two treatment groups: C. zeylanicum (0.5 mg/mL), n = 18; nystatin (100,000IU/mL), n = 18. The efficacy of the products was evaluated by two parameters: (a) clinical evolution recorded by calibrated examiners (Kappa = 0.822) according to Newton's classification and (b) reduction of colony-forming units/mL. Mycological and clinical parameters were analyzed before and at 15 days after treatment. Clinical examination of the mucosa showed that C. zeylanicum (p < 0.0339) and nystatin (p < .0139) had efficacy, resulting in a reduction of signs and symptoms (Mann-Whitney test). Mycological analysis showed that C. zeylanicum caused a reduction of 61% and 33% of Candida spp., isolates oral mucosa and dentures, respectively. Candida tropicalis strains were eliminated after C. zeylanicum, in both sites. The participants reported a pleasant taste and few product-related complaints. CONCLUSION: C. zeylanicum EO and nystatin exhibited clinical efficacy, according to the Newton classification, and reducing in Candida spp. The clinical trial has been registered (Registration number: NBR-33s6 × 5, ensaiosclinicos.gov.br).

Antifungal efficacy of atorvastatin-containing emulgel in the treatment of oral and vulvovaginal candidiasis.

Drug repositioning has been an important ally in the search for new antifungal drugs. Statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are promissory candidates to be repositioned to treat mycoses. In this study we evaluated the antifungal activity of atorvastatin by in vitro tests to determine the minimum inhibitory concentration against azole resistant Candida albicans and its mechanisms of action. Moreover, the efficacy of both atorvastatin-loaded oral and vaginal emulgels (0.75%, 1.5% and 3% w/w) was evaluated by means of in vivo experimental models of oral and vulvovaginal candidiasis, respectively. The results showed that atorvastatin minimal inhibitory concentration against C. albicans was 31.25 µg/ml. In oral candidiasis experiments, the group treated with oral emulgel containing 3.0% atorvastatin showcased total reduction in fungal load after nine days of treatment. Intravaginal delivery atorvastatin emulgel showed considerable effectiveness at the concentration of 3% (65% of fungal burden reduction) after nine days of treatment. From these findings, it is possible to assert that atorvastatin may be promising for drug repositioning towards the treatment of these opportunistic mycoses.

Atorvastatin is a statin drug that presents antifungal activity. This study showed that atorvastatin-containing oral and vaginal emulgels were able to treat vulvovaginal and oral candidiasis of infected animal model. Therefore, we showcased that atorvastatin may be a possible therapeutic agent in order to be a used to control opportunistic mucosal fungal infections caused by Candida albicans.