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Frontiers in Pharmacology 2021Miconazole is effective in treating inflammatory skin conditions and has well-established antifungal effects. To elucidate the underlying mechanisms mediating its...
Miconazole is effective in treating inflammatory skin conditions and has well-established antifungal effects. To elucidate the underlying mechanisms mediating its additional beneficial effects, we assessed whether miconazole influences the inflammation induced by 27-hydroxycholesterol (27OHChol), an oxygenated cholesterol derivative with high proinflammatory activity, using THP-1 monocytic cells. Miconazole dose-dependently inhibited the expression of proinflammatory markers, including CCL2 and CCR5 ligands such as CCL3 and CCL4, and impaired the migration of monocytic cells and CCR5-positive T cells. In the presence of 27OHChol, miconazole decreased CD14 surface levels and considerably weakened the lipopolysaccharide response. Furthermore, miconazole blocked the release of soluble CD14 and impaired the transcription of the matrix metalloproteinase-9 gene and secretion of its active gene product. Additionally, it downregulated the expression of ORP3 and restored the endocytic function of THP-1 cells. Collectively, these findings indicate that miconazole regulates the 27OHChol-induced expression of proinflammatory molecules in monocytic cells, thereby suppressing inflammation in an oxysterol-rich milieu.
PubMed: 34744703
DOI: 10.3389/fphar.2021.691019 -
Pharmaceutics Dec 2021Dapivirine (DPV) is a potent NNRTI used to prevent the sexual transmission of HIV. In a phase 1 trial (IPM 028), the concomitant use of a DPV vaginal ring and an...
Dapivirine (DPV) is a potent NNRTI used to prevent the sexual transmission of HIV. In a phase 1 trial (IPM 028), the concomitant use of a DPV vaginal ring and an antifungal miconazole (MIC) vaginal capsule was found to increase the systemic exposure to DPV in women, suggesting a potential for drug-drug interactions. This study's objective was to investigate the mechanism of DPV-MIC interactions using drug-metabolizing enzymes (DMEs; CYPs and UGTs) that are locally expressed in the female reproductive tract (FRT). In vitro studies were performed to evaluate the metabolism of DPV and its inhibition and induction potential with DMEs. In addition, the impact of MIC on DPV metabolism and the inhibitory potential of DPV with DMEs were studied. Our findings suggest that DPV is a substrate of CYP1A1 and CYP3A4 enzymes and that MIC significantly decreased the DPV metabolism by inhibiting these two enzymes. DPV demonstrated potent inhibition of CYP1A1 and moderate/weak inhibition of the six CYP and eight UGT enzymes evaluated. MIC showed potent/moderate inhibition of seven CYP enzymes and weak/no inhibition of eight UGT enzymes. The combination of DPV and MIC showed potent inhibition of seven CYP enzymes (1A1, 1A2, 1B1, 2B6, 2C8, 2C19, and 3A4) and four UGT enzymes (1A3, 1A6, 1A9, and 2B7). DPV was not an inducer of CYP1A2, CYP2B6, and CYP3A4 enzymes in primary human hepatocytes. Therefore, the increased systemic concentrations of DPV observed in IPM 028 were likely due to the reduced metabolism of DPV because of CYP1A1 and CYP3A4 enzymes inhibition by MIC in the FRT.
PubMed: 34959473
DOI: 10.3390/pharmaceutics13122193 -
Journal of Dentistry Oct 2022This study assessed the effects of chitosan (CS) on microcosm biofilms derived from saliva of patients with Candida-associated denture stomatitis.
OBJECTIVE
This study assessed the effects of chitosan (CS) on microcosm biofilms derived from saliva of patients with Candida-associated denture stomatitis.
METHODS
Five removable denture wearers with denture stomatitis were included in the study. The minimum inhibitory concentration (MIC) of CS against clinical isolates of Candida albicans was determined according to the broth microdilution method. Pooled saliva from the donors was used as an inoculum for the formation of biofilms, which were developed during 72 h on acrylic surfaces in the Amsterdam Active Attachment model. The biofilms were then treated with different concentrations of CS, and the antibiofilm effects were evaluated through the quantification of colony-forming units (CFUs), total biomass (TB), metabolic activity (MA), lactic acid production (LAP), and cell viability (by confocal laser scanning microscopy). Chlorhexidine, miconazole, and nystatin were tested as positive controls, while the negative control (NC) was the untreated biofilm. Data were analyzed by 1-way ANOVA and Fischer LSD's post hoc test (α=0.05).
RESULTS
MIC values of CS ranged from 500 to 800 µg/mL. For CFUs, 2500 µg/mL CS was the most effective treatment in reducing total anaerobes, mutans streptococci, and Lactobacillus spp., significantly differing from the controls. For C. albicans CFUs, CS and positive controls did not differ from each other but led to significant reductions compared to NC. Regarding TB, MA, LAP, and cell viability, 2500 µg/mL CS promoted the greatest reductions compared to NC.
CONCLUSION
CS has similar or superior effects to conventional active principles on important parameters of oral candidiasis microcosm biofilms.
CLINICAL RELEVANCE
The antibiofilm effects of CS show that this compound has great potential to improve the clinical condition of denture stomatitis patients, and formulations containing this natural polymer could be useful for controlling oral candidiasis.
Topics: Humans; Acrylic Resins; Antifungal Agents; Biofilms; Candida albicans; Candidiasis, Oral; Chitosan; Chlorhexidine; Lactic Acid; Miconazole; Nystatin; Stomatitis, Denture
PubMed: 35914573
DOI: 10.1016/j.jdent.2022.104246 -
ACS Omega Sep 2020The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586...
The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586 FDA-approved drugs was screened against , a representative of the complex. Three compounds were found to have previously undiscovered antibacterial properties against : antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three drugs were tested against a wide range of Gram-positive and Gram-negative bacteria and confirmed to have broad-spectrum antibacterial properties. Combinations of these three drugs were also tested against the same bacteria, and two novel combination therapies with synergistic effects were discovered. In the future, antibacterial properties of these three drugs and two combination therapies will be evaluated against pathogenic bacteria using an animal model.
PubMed: 32984715
DOI: 10.1021/acsomega.0c03211 -
Journal of Physiology and Pharmacology... Aug 2014Oral candidiasis in the form of Candida-associated denture stomatitis (CaDS) is associated with Candida adhesion and biofilm formation on the fitting surface of poly...
Oral candidiasis in the form of Candida-associated denture stomatitis (CaDS) is associated with Candida adhesion and biofilm formation on the fitting surface of poly (methyl methacrylate) (PMMA) dentures. Candida biofilms show considerable resistance to most conventional antifungal agents, a phenomenon that is considered a developmental-phase-specific event that may help explain the high recurrence rates associated with CaDS. The aim of this study was to examine the activity of miconazole towards in vitro-grown mature Candida biofilms formed on heat-cured PMMA discs as a standardized model. The effect of miconazole nitrate on Candida biofilms developed on acrylic discs was determined for C. albicans MYA-2732 (ATCC), C. glabrata MYA-275 (ATCC), and clinical isolates, C. albicans 6122/06, C. glabrata 7531/06, C. tropicalis 8122/06, and C. parapsilosis 11375/07. Candida biofilms were developed on heat-cured poly(methyl methacrylate) discs and treated with miconazole (0.5 - 96 μg/ml). The metabolic activity of the biofilms was measured by the XTT reduction assay. The minimum inhibitory concentrations (MICs) of miconazole against Candida species were determined by the microdilution method. The MICs for miconazole for the investigated strains ranged from 0.016-32 μg/ml. Treatment with miconazole resulted in a significant reduction of biofilm metabolic activity for all strains. The highest inhibition was observed at 96 μg/ml miconazole. In the case of C. glabrata MYA-275 and C. tropicalis 8122/06 this corresponded to 83.7% and 75.4% inhibition, respectively. The lowest reduction was observed for C. parapsilosis 11375/07-46.1%. For all Candida strains there was a strong correlation between MIC values and miconazole concentrations corresponding to a reduction of metabolic activity of the biofilm by 50%. Miconazole exhibits high antifungal activity against Candida biofilms developed on the surface of PMMA discs. The study provides support for the use of miconazole as an effective agent for the treatment of CaDS.
Topics: Antifungal Agents; Biofilms; Candida; Dentures; Miconazole; Microbial Sensitivity Tests; Polymethyl Methacrylate; Tetrazolium Salts
PubMed: 25179092
DOI: No ID Found -
Folia Microbiologica Dec 2023The rising number of invasive fungal infections caused by drug-resistant Candida strains is one of the greatest challenges for the development of novel antifungal...
The rising number of invasive fungal infections caused by drug-resistant Candida strains is one of the greatest challenges for the development of novel antifungal strategies. The scarcity of available antifungals has drawn attention to the potential of natural products as antifungals and in combinational therapies. One of these is catechins-polyphenolic compounds-flavanols, found in a variety of plants. In this work, we evaluated the changes in the susceptibility of Candida glabrata strain characterized at the laboratory level and clinical isolates using the combination of catechin and antifungal azoles. Catechin alone had no antifungal activity within the concentration range tested. Its use in combination with miconazole resulted in complete inhibition of growth in the sensitive C. glabrata isolate and a significant growth reduction in the azole resistant C. glabrata clinical isolate. Simultaneous use of catechin and miconazole leads to increased intracellular ROS generation. The enhanced susceptibility of C. glabrata clinical isolates to miconazole by catechin was accompanied with the intracellular accumulation of ROS and changes in the plasma membrane permeability, as measured using fluorescence anisotropy, affecting the function of plasma membrane proteins.
Topics: Antifungal Agents; Miconazole; Candida glabrata; Catechin; Reactive Oxygen Species; Microbial Sensitivity Tests; Drug Resistance, Fungal; Azoles
PubMed: 37145224
DOI: 10.1007/s12223-023-01061-z -
The International Journal of... Nov 2022Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear.
BACKGROUND
Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear.
METHODS
We evaluated the cooperative function of APP/PS1 transgenic AD model mice at ages 2, 5, and 8 months by using a cooperative drinking task. We examined neuropathologic changes in the medial prefrontal cortex (mPFC). Another experiment was designed to observe whether miconazole, which has a repairing effect on myelin sheath, could promote the cooperative ability of APP/PS1 mice in the early AD-like stage. We also investigated the protective effects of miconazole on cultured mouse cortical oligodendrocytes exposed to human amyloid β peptide (Aβ1-42).
RESULTS
We observed an age-dependent impairment of cooperative water drinking behavior in APP/PS1 mice. The AD mice with cooperative dysfunction showed decreases in myelin sheath thickness, oligodendrocyte nuclear heterochromatin percentage, and myelin basic protein expression levels in the mPFC. The cooperative ability was significantly improved in APP/PS1 mice treated with miconazole. Miconazole treatment increased oligodendrocyte maturation and myelin sheath thickness without reducing Aβ plaque deposition, reactive gliosis, and inflammatory factor levels in the mPFC. Miconazole also protected cultured oligodendrocytes from the toxicity of Aβ1-42.
CONCLUSIONS
These results demonstrate that mPFC hypomyelination is involved in the cooperative deficits of APP/PS1 mice. Improving myelination through miconazole therapy may offer a potential therapeutic approach for early intervention in AD.
Topics: Humans; Mice; Animals; Alzheimer Disease; Amyloid beta-Peptides; Miconazole; Mice, Inbred C57BL; Amyloid beta-Protein Precursor; Plaque, Amyloid; Mice, Transgenic; Disease Models, Animal; Presenilin-1
PubMed: 36112386
DOI: 10.1093/ijnp/pyac061 -
Journal of Cancer Research and... 2014Anticancer properties of artemisinin and its derivatives have been shown in many experiments.
CONTEXT
Anticancer properties of artemisinin and its derivatives have been shown in many experiments.
AIMS
Addition of butyric acid, miconazole, and iron to this traditional drug has been done in order to enhance its anticancer potency.
MATERIALS AND METHODS
Cell lines 5637 and 4T1, were cultivated and classified into 13 groups of three each. Different doses of artemisinin with constant doses of iron, miconazole and butyric acid, were added to the cultures. At the end of exposure pathological and enzymatic studies were performed.
RESULTS
In four groups treated with different doses of artemisinin and iron, dose-dependent changes were observed. These changes included apoptosis and necrosis with dominance of apoptosis. The supernatant lactate dehydrogenase (LDH) level was increased in a dose-dependent manner, but there was no significant increase in the cell fraction of malonyldialdehyde (MDA) or LDH. In four other groups, which received miconazole, butyric acid and iron in addition to different doses of artemisinin, necrosis was more prominent than apoptosis, and the MDA level did not show any significant change, but LDH was increased. The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis.
CONCLUSIONS
A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.
Topics: Animals; Antineoplastic Agents; Apoptosis; Artemisinins; Breast Neoplasms; Butyric Acid; Cell Line, Tumor; Cytoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Female; Humans; Iron; L-Lactate Dehydrogenase; Malondialdehyde; Mice; Miconazole; Necrosis; Urinary Bladder Neoplasms
PubMed: 25579554
DOI: 10.4103/0973-1482.137975 -
Antimicrobial Agents and Chemotherapy Jan 2015Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the...
Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albicans biofilm-related infections.
Topics: Amphotericin B; Antifungal Agents; Artemisinins; Artesunate; Biofilms; Candida albicans; Candidiasis; Caspofungin; Drug Synergism; Echinocandins; Fluconazole; Hexachlorophene; Lipopeptides; Miconazole; Microbial Sensitivity Tests; Pyrvinium Compounds; Reactive Oxygen Species
PubMed: 25367916
DOI: 10.1128/AAC.04229-14 -
Brain and Behavior Oct 2019Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most...
BACKGROUND
Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most widely used antifungal drugs; the aims of the study were to investigate the effects of miconazole during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury.
METHODS
We established peripheral nerve crush model and investigated the effects of miconazole by multiple aspects. We further studied the potential mechanism of action of miconazole by Western blotting, fluorescence immunohistochemistry, and PCR analysis.
RESULTS
Miconazole improves the symptoms of crushed nerve by improving inflammatory cell infiltration and demyelinating myelin of sciatic nerve. Affected by miconazole, the proportion of inflammatory M1 macrophages in the distal part of the sciatic nerve was reduced, and the proportion of anti-inflammatory M2 macrophages was increased. Finally, the neuroprotective properties of miconazole may be regulated by the nuclear factor (NF)-κB pathway.
CONCLUSIONS
Our data suggest that miconazole can effectively alleviate PNI, and the mechanism involves mediating a phenotype change of M1/ M2 macrophages. Thus, miconazole may represent a potential therapeutic intervention for nerve crush injury.
Topics: Animals; Crush Injuries; Cytochrome P-450 CYP2C9 Inhibitors; Disease Models, Animal; Macrophages; Male; Mice; Mice, Inbred C57BL; Miconazole; NF-kappa B; Nerve Crush; Nerve Regeneration; Peripheral Nerve Injuries; Phenotype; Sciatic Nerve
PubMed: 31486271
DOI: 10.1002/brb3.1400