RESUMO
The antimalarial drug Mefloquine has demonstrated antifungal activity against growth and virulence factors of Candida albicans. The current study focused on the identification of Mefloquine's mode of action in C. albicans by performing cell susceptibility assay, biofilm assay, live and dead assay, propidium iodide uptake assay, ergosterol quantification assay, cell cycle study, and gene expression studies by RT-PCR. Mefloquine inhibited the virulence factors in C. albicans, such as germ tube formation and biofilm formation at 0.125 and 1 mg/ml, respectively. Mefloquine-treated cells showed a decrease in the quantity of ergosterol content of cell membrane in a concentration-dependent manner. Mefloquine (0.25 mg/ml) arrested C. albicans cells at the G2/M phase and S phase of the cell cycle thereby preventing the progression of the normal yeast cell cycle. ROS level was measured to find out oxidative stress in C. albicans in the presence of mefloquine. The study revealed that, mefloquine was found to enhance the ROS level and subsequently oxidative stress. Gene expression studies revealed that mefloquine treatment upregulates the expressions of SOD1, SOD2, and CAT1 genes in C. albicans. In vivo, the antifungal efficacy of mefloquine was confirmed in mice for systemic candidiasis and it was found that there was a decrease in the pathogenesis of C. albicans after the treatment of mefloquine in mice. In conclusion, mefloquine can be used as a repurposed drug as an alternative drug against Candidiasis.
Assuntos
Antifúngicos , Candida albicans , Candidíase , Mefloquina , Fatores de Virulência , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Candida albicans/patogenicidade , Candida albicans/crescimento & desenvolvimento , Animais , Mefloquina/farmacologia , Camundongos , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Candidíase/microbiologia , Candidíase/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Espécies Reativas de Oxigênio/metabolismo , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Ergosterol/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
Cruciferous vegetables and mustard oil are rich in the glucosinolate group of molecules. Isothiocyanates are an important group of glucosinolate derivatives. These derivatives have various bioactive properties, including antioxidant, antibacterial, anticarcinogenic, antifungal, antiparasitic, herbicidal and antimutagenic activity. Previous studies indicate that regular intake of such vegetables may considerably reduce the incidence of various types of cancer. These studies have inspired studies where the bioactive agents of these plants have been isolated and explored for their therapeutic applications. The use of these bioactive compounds as antifungals could be a new therapeutic approach against human pathogenic fungi. Isothiocyanates have been studied for their antifungal activity and have the potential to be used for antifungal therapy.
Vegetables like cabbage, cauliflower and broccoli have a distinct flavor because of chemicals called glucosinolates. Whenever we cut and eat these vegetables, glucosinolates are broken down into isothiocyanates. Glucosinolates and isothiocyanates have health benefits because they stop the growth of bacteria, parasites and fungi that cause disease, such as Candida albicans. They may also prevent cancer, as regularly eating these vegetables has been shown to reduce the development of some types of cancer in humans. Investigation is needed to explore how glucosinolates and isothiocyanates could be used to treat fungal infections.
