Antifungal Activity of Natural Compounds vs. Candida spp.: A Mixture of Cinnamaldehyde and Eugenol Shows Promising In Vitro Results

Candida spp. are commensal organisms of the skin, mucous membranes, gastrointestinal tract, blood, and vagina of animals and humans. In recent decades, the incidence of human fungal infections has increased, with Candida spp. (mainly C. albicans) infections being the most frequent, and the treatment of fungal infections is still a clinical challenge. Colonization of the human gastrointestinal tract by Candida spp. is significant because infections (e.g., candidemia and vulvovaginal candidiasis) frequently arise from commensal microorganisms. The aim of this study was to test in vitro the antifungal activity and the eventual synergistic effect of five pure components of essential oils: cinnamaldehyde, α-pinene, limonene, eucalyptol, and eugenol. These compounds were tested on 18 Candida strains (15 C. albicans, 2 C. glabrata, and 1 C. lusitaniae) derived from a culture collection of vaginal clinical strains. Methods: Fungistatic activity was evaluated using the disk diffusion method. For fungicidal activity, microdilution and time–kill curve protocols were set up. The checkerboard method was chosen to evaluate a possible synergistic effect of these compounds when mixed. Results: Cinnamaldehyde and eugenol gave the best results, inhibiting all the Candida strains and showing a highly additive effect (FICI 0.625). The cinnamaldehyde inhibition zone (IZ), MIC, and MFC means were 69 mm, 50.05 mg/L, and 109.26 mg/L respectively. Cinnamaldehyde led to the total loss of viable Candida cells within 4 h. Eugenol IZ, MIC, and MFC means were 35.2 mm, 455.42 mg/L, and 690.09 mg/L, respectively. Eugenol led to the total loss of viable fungal cells within 1 h. Treatment with α-pinene inhibited 88.9% of Candida strains, with an IZ mean of 21.2 mm, a MIC mean of 195.41 mg/L, and a MFC mean of 251.27 mg/L; this compound led to the total loss of viable fungal cells only after 24 h. Limonene inhibited only 33.3% of the tested strains and eucalyptol did not produce an inhibition halo, so these compounds were not tested further. Conclusions: These characteristics, together with the well-known safety of cinnamaldehyde and eugenol for human use, make these two natural compounds the perfect candidates for the treatment of candidiasis. This was a pilot study, the purpose of which was to evaluate the best composition of a mixture to be used against intestinal and vulvovaginal candidiasis; in vivo studies are needed to confirm these very encouraging results.

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QSAR Study of Some 1,3-Oxazolylphosphonium Derivatives as New Potent Anti-Candida Agents and Their Toxicity Evaluation

Current Drug Discovery Technologies ◽

10.2174/1570163815666180418145422 ◽

2019 ◽

Vol 16 (2) ◽

pp. 204-209

Author(s):

Maria M. Trush ◽

Vasyl Kovalishyn ◽

Alla D. Ocheretniuk ◽

Oleksandr L. Kobzar ◽

Maryna V. Kachaeva ◽

...

Keyword(s):

Fungal Infections ◽

Electric Organ ◽

Biological Marker ◽

Diffusion Method ◽

Phosphonium Salts ◽

Candida Spp ◽

Qsar Study ◽

Disk Diffusion Method ◽

Qsar Models

Background: The incidence of invasive fungal infections caused by Candida spp. has increased continuously in recent decades, especially in populations of immunocompromised patients or individuals hospitalized with serious underlying diseases. Therefore, the goal of our study was the search for new potent Candida albicans inhibitors via the development of QSAR models that could speed up this search process. A number of the most promising 1,3-oxazol-4-yltriphenylphosphonium derivatives with predicted activities were synthesized and experimentally tested. Furthermore, the toxicity of the studied compounds was determined in vitro using acetylcholinesterase enzyme as a biological marker. Methods: The classification QSAR models were created using Random Forests (WEKA-RF), k-Nearest Neighbors and Associative Neural Networks methods and different combinations of descriptors on the Online Chemical Modeling Environment (OCHEM) platform. Аntifungal properties of the investigated compounds were performed using standard disk diffusion method. The enzyme inhibitory action of the compounds was determined by modified Ellman's method using acetylcholinesterase from the electric organ of Electrophorus electricus. Results: Three classification QSAR models were developed by the WEKA-RF, k-NN and ASNN methods using the ALogPS, E-State indices and Dragon v.7 descriptors. The predictive ability of the models was tested through cross-validation, giving a balanced accuracy BA = 80-91%. All compounds demonstrated good antifungal properties against Candida spp. and slight inhibition of the acetylcholinesterase activity. Conclusion: The high percentage of coincidence between the QSAR predictions and the experimental results confirmed the high predictive power of the developed QSAR models that can be applied as tools for finding new potential inhibitors against Candida spp. Furthermore, 1,3-oxazol-4- yl(triphenyl)phosphonium salts could be considered as promising candidates for the treatment of candidiasis and the disinfection of medical equipment.

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In vitro synergism of simvastatin and fluconazole against Candida species

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652012000400003 ◽

2012 ◽

Vol 54 (4) ◽

pp. 197-199 ◽

Cited By ~ 11

Author(s):

Everardo Albuquerque Menezes ◽

Antônio Alexandre de Vasconcelos Júnior ◽

Carlla Lorena Façanha Silva ◽

Fábio Ximenes Plutarco ◽

Maria da Conceição dos Santos Oliveira Cunha ◽

...

Keyword(s):

Synergistic Effect ◽

Susceptibility Testing ◽

Inhibitory Concentration ◽

Fungal Infections ◽

Candida Spp ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Antifungal Action ◽

Systemic Infections

Systemic fungal infections are responsible for high mortality rates. Several species of fungi may be involved, but Candida spp. is the most prevalent. Simvastatin is used to lower cholesterol and also exhibits antifungal action. The aim of this study was to evaluate the synergistic action of simvastatin with fluconazole against strains of Candida spp. Susceptibility testing was performed according to protocol M27-A3, by broth microdilution method and the synergistic effect of simvastatin and fluconazole was calculated based on FICI (Fractional Inhibitory Concentration Index). Eleven strains were evaluated, and simvastatin showed a synergistic effect with fluconazole against 10 (91%) of the Candida spp. strains tested. Simvastatin may be a valuable drug in the treatment of systemic infections caused by Candida spp.

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REFRACTORY FUNGAL VAGINITIS TREATED BY TOPICAL AMPHOTERICIN B. Review

Medical Science of Ukraine (MSU) ◽

10.32345/2664-4738.2.2020.10 ◽

2020 ◽

Vol 16 (2) ◽

pp. 55-58

Author(s):

Falah Hasan Obayes AL-Khikani

Keyword(s):

Antifungal Activity ◽

Side Effects ◽

Amphotericin B ◽

Intravenous Injection ◽

Fungal Infections ◽

Wide Spectrum ◽

Candida Spp

Vaginitis is a common problem for women regarding a worldwide health challenge with many side effects. Vaginitis is among the most visiting to gynecology clinics. About 75% of all reproductive women had at least one fungal vaginitis infection in their life, and more than 40% will have two or more than two. Candida spp is the most prevalent in fungal vaginitis, while reports for unusual fungi were observed as mucor spp. Amphotericin B (AmB) belongs to the polyene group has a wide spectrum in vitro and in vivo antifungal activity. All of the known available formulas of AmB are administrated via intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary development including topical vaginal AmB. Due to the revealing of antimicrobial-resistant fungi in recent years, this study explains the role of topical AmB in treating refractory fungi vaginitis that may not a response to other drugs reported in many cases that may help researchers to develop new effective formula of AmB regarding fungal vaginitis.

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In Vitro Activity of Lawsonia inermis (Henna) on Some Pathogenic Fungi

Journal of Mycology ◽

10.1155/2014/375932 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Elham Abdelbasit Suleiman ◽

Elbasheir Ahmed Mohamed

Keyword(s):

Antifungal Activity ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Diffusion Method ◽

In Vitro Activity ◽

Lawsonia Inermis ◽

Traditional Use ◽

Yeast Strains ◽

Inhibition Concentration

The present study was conducted to investigate antifungal activity of Lawsonia inermis (Henna plant). Leaf samples of the plant were collected from Eastern Nile of Khartoum State, Sudan. Ethanol and petroleum ether extracts were obtained by maceration (cold method). The extracts were bioassayed in vitro to know their bioactivity to inhibit the growth of tested fungi. The cup-plate agar diffusion method was adopted to assess the antifungal activity of the extracts against tested yeasts, while agar incorporated method was used for other molds. Both extracts revealed antifungal activity against all yeast strains except Pichia fabianii which was found resistant to both ethanol and ether extracts. The results displayed antifungal activity against tested fungi. Minimum inhibition concentration (MIC) of 5, 7.5, and 10 mg/mL was found to inhibit the growth of tested dermatophytes. The obtained results revealed antifungal activity of Henna leaves extracts which support the traditional use of Henna in therapy of fungal infections. The possibility of therapeutic use of Sudanese Henna as antifungal agent is recommended.

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In Vitro Antifungal and Topical Anti-Inflammatory Properties of Essential Oil from Wild-Growing Thymus vulgaris (Lamiaceae) Used for Medicinal Purposes in Algeria: A New Source of Carvacrol

Scientia Pharmaceutica ◽

10.3390/scipharm88030033 ◽

2020 ◽

Vol 88 (3) ◽

pp. 33 ◽

Cited By ~ 1

Author(s):

Mohamed Nadjib Boukhatem ◽

Noureldien H. E. Darwish ◽

Thangirala Sudha ◽

Siham Bahlouli ◽

Dahbia Kellou ◽

...

Keyword(s):

Antifungal Activity ◽

Essential Oil ◽

Fungal Infections ◽

Positive Control ◽

Diffusion Method ◽

Thymus Vulgaris ◽

Dilution Method ◽

Agar Dilution Method ◽

Anti Inflammatory

The aim of this study is to investigate the Thymus vulgaris essential oil (TVEO) as an antifungal agent in aromatherapy and/or as an active ingredient in the prevention or management of topical inflammatory diseases. The chemical composition of TVEO was determined with gas chromatography and revealed the presence of 25 compounds. Carvacrol was found to be the major component (56.8%). Antifungal action of TVEO was determined in vitro by using different methods. By the disc diffusion method, TVEO showed more potent antifungal activity against Candida strains than the positive control. The diameter of inhibition zone (DIZ) varied from 34 to 60 mm for Candida yeasts. Significantly higher antifungal activity was observed in the vapor phase at lower quantities. Candida albicans and C. parapsilosis were the most susceptible strains to the oil vapor with DIZ varying from 35 to 90 mm. The minimum inhibitory concentrations (MIC) of yeast were determined with an agar dilution method and revealed that MIC varied from 0.3 to 0.15 µL/mL for yeast species. The topical anti-inflammatory potential of TVEO was also explored in vivo with the croton oil-induced ear edema assay. TVEO exhibited a potent anti-inflammatory effect at all doses (100, 10 and 2 mg/kg), which were statistically similar (p > 0.05) to the positive control. This activity was also confirmed at the cellular level with histopathology analysis. Our results suggest the potential application of this carvacrol-rich TVEO in the prevention and management of fungal infections and topical inflammation and deserve further investigation for clinical applications. Furthermore, while the mode of action remains mainly undetermined and should be studied.

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Smart Gn-Keto Nanohybrid Embedded Topical System for Effective Management of Dermatophytosis

Drug Delivery Letters ◽

10.2174/2210303108666181105112557 ◽

2019 ◽

Vol 9 (1) ◽

pp. 21-28

Author(s):

Nisha Sharma ◽

Shashikiran Misra

Keyword(s):

Antifungal Activity ◽

Fungal Infections ◽

High Surface ◽

High Surface Area ◽

Vital Role ◽

Common Disease ◽

Microdilution Method ◽

Enhanced Solubility ◽

Bioactive Agents

Background and Objectives: Dermatophytosis (topical fungal infection) is the 4th common disease in the last decade, affecting 20-25% world’s population. Patients of AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to dermatophytosis. The conventional topical dosage proves effective as prophylactic in preliminary stage. In the advanced stage, the therapeutics interacts with healthy tissues before reaching the pathogen site, showing undesirable effects, thus resulting in pitiable patient compliance. The youngest carbon nano-trope “Graphene” is recently used to manipulate bioactive agents for therapeutic purposes. Here, we explore graphene via smart engineering by virtue of high surface area and high payload for therapeutics and developed graphene–ketoconazole nanohybrid (Gn-keto) for potent efficacy towards dermatophytes in a controlled manner. </P><P> Methods: Polymethacrylate derivative Eudragit (ERL100 and ERS 100) microspheres embedded with keto and Gn-keto nanohybrid were formulated and characterized through FTIR, TGA, and SEM. In vitro drug release and antifungal activity of formulated Gn-keto microspheres were assessed for controlled release and better efficacy against selected dermatophytes. </P><P> Results: Presence of numerous pores within the surface of ERL100 microspheres advocated enhanced solubility and diffusion at the site of action. Controlled diffusion across the dialysis membrane was observed with ERS100 microspheres owing to the nonporous surface and poor permeability. Antifungal activity against T. rubrum and M. canis using microdilution method focused on a preeminent activity (99.785 % growth inhibition) of developed nanohybrid loaded microspheres as compared to 80.876% of keto loaded microspheres for T. rubrum. The culture of M. canis was found to be less susceptible to formulated microspheres. Conclusion: Synergistic antifungal activity was achieved by nanohybrid Gn-Keto loaded microspheres against selected topical fungal infections suggesting a vital role of graphene towards fungi.

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The Impact of Gelatin on the Pharmaceutical Characteristics of Fucoidan Microspheres with Posaconazole

Materials ◽

10.3390/ma14154087 ◽

2021 ◽

Vol 14 (15) ◽

pp. 4087

Author(s):

Marta Szekalska ◽

Aleksandra Citkowska ◽

Magdalena Wróblewska ◽

Katarzyna Winnicka

Keyword(s):

Antifungal Activity ◽

Drug Release ◽

Spray Drying ◽

Fungal Infections ◽

Drug Loading ◽

High Surface ◽

Vaginal Fluid ◽

Sustained Drug Release ◽

Candida Spp ◽

The Impact

Fungal infections and invasive mycoses, despite the continuous medicine progress, are an important globally therapeutic problem. Multicompartment dosage formulations (e.g., microparticles) ensure a short drug diffusion way and high surface area of drug release, which as a consequence can provide improvement of therapeutic efficiency compared to the traditional drug dosage forms. As fucoidan is promising component with wide biological activity per se, the aim of this study was to prepare fucospheres (fucoidan microparticles) and fucoidan/gelatin microparticles with posaconazole using the one-step spray-drying technique. Pharmaceutical properties of designed fucospheres and the impact of the gelatin addition on their characteristics were evaluated. An important stage of this research was in vitro evaluation of antifungal activity of developed microparticles using different Candida species. It was observed that gelatin presence in microparticles significantly improved swelling capacity and mucoadhesiveness, and provided a sustained POS release. Furthermore, it was shown that gelatin addition enhanced antifungal activity of microparticles against tested Candida spp. strains. Microparticles formulation GF6, prepared by the spray drying of 20% fucoidan, 5% gelatin and 10% Posaconazole, were characterized by optimal mucoadhesive properties, high drug loading and the most sustained drug release (after 8 h 65.34 ± 4.10% and 33.81 ± 5.58% of posaconazole was dissolved in simulated vaginal fluid pH 4.2 or 0.1 M HCl pH 1.2, respectively).

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Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro

Pharmaceutics ◽

10.3390/pharmaceutics13070998 ◽

2021 ◽

Vol 13 (7) ◽

pp. 998

Author(s):

Virgínia Barreto Lordello ◽

Andréia Bagliotti Meneguin ◽

Sarah Raquel de Annunzio ◽

Maria Pía Taranto ◽

Marlus Chorilli ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Enterococcus Faecium ◽

Potato Starch ◽

Oral Candidiasis ◽

Candida Spp ◽

Sem Images ◽

Control Film ◽

In Vitro Antifungal Activity

Background: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. Methods and Results: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g−1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. Conclusion: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

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An In Vitro Study on the Antimicrobial Properties of Essential Oil Modified Resin Composite against Oral Pathogens

Materials ◽

10.3390/ma13194383 ◽

2020 ◽

Vol 13 (19) ◽

pp. 4383

Author(s):

Barbara Lapinska ◽

Aleksandra Szram ◽

Beata Zarzycka ◽

Janina Grzegorczyk ◽

Louis Hardan ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antibacterial Activity ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Resin Composite ◽

Antimicrobial Properties ◽

In Vitro Study ◽

Diffusion Method ◽

Oral Pathogens

Modifying the composition of dental restorative materials with antimicrobial agents might induce their antibacterial potential against cariogenic bacteria, e.g., S.mutans and L.acidophilus, as well as antifungal effect on C.albicans that are major oral pathogens. Essential oils (EOs) are widely known for antimicrobial activity and are successfully used in dental industry. The study aimed at evaluating antibacterial and antifungal activity of EOs and composite resin material (CR) modified with EO against oral pathogens. Ten EOs (i.e., anise, cinnamon, citronella, clove, geranium, lavender, limette, mint, rosemary thyme) were tested using agar diffusion method. Cinnamon and thyme EOs showed significantly highest antibacterial activity against S.mutans and L.acidophilus among all tested EOs. Anise and limette EOs showed no antibacterial activity against S.mutans. All tested EOs exhibited antifungal activity against C.albicans, whereas cinnamon EO showed significantly highest and limette EO significantly lowest activity. Next, 1, 2 or 5 µL of cinnamon EO was introduced into 2 g of CR and microbiologically tested. The modified CR showed higher antimicrobial activity in comparison to unmodified one. CR containing 2 µL of EO showed the best antimicrobial properties against S.mutans and C.albicans, while CR modified with 1 µL of EO showed the best antimicrobial properties against L.acidophilus.

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Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

Medical Mycology ◽

10.1093/mmy/myab054 ◽

2021 ◽

Author(s):

Rodrigo L Fabri ◽

Jhamine C O Freitas ◽

Ari S O Lemos ◽

Lara M Campos ◽

Irley O M Diniz ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Antifungal Activity ◽

Cell Membrane ◽

Multidrug Resistant ◽

Fungal Strain ◽

Vulvovaginal Candidiasis ◽

Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

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