In vitro evaluation of cytotoxic potential of essential oil extracted from leaves of Croton heliotropiifolius Kunth in human tumor cells.

Croton heliotropiifolius Kunth, popularly known as "velame," is a shrub that resides in northeastern Brazil. The essential oil of C. heliotropiifolius contains high concentrations of volatile compounds in the leaves and is widely used in folk medicine for many purposes as an antiseptic, analgesic, sedative, and anti-inflammatory agent. Due to the apparent limited amount of information, the aim of this study was to determine the cytotoxic potential of essential oil extracted from leaves of C. heliotropiifolius, utilizing different human cancer cell lines (HL-60, leukemia; HCT-116, colon; MDA-MB435, melanoma; SF295, glioblastoma) and comparison to murine fibroblast L929 cell line. The chemical characterization of the essential oil revealed the presence of large amounts of monoterpenes and sesquiterpenes, the majority of which were aristolene (22.43%), germacrene D (11.38%), ɣ-terpinene (10.85%), and limonene (10.21%). The essential oil exerted significant cytotoxicity on all cancer cells, with low activity on murine L929 fibroblasts, independent of disruption of cell membranes evidenced by absence of hemolytic activity. The cytotoxicity identified was associated with oxidative stress, which culminated in mitochondrial respiration dysfunction and direct or indirect DNA damage (strand breaks and oxidative damage), triggering cell death via apoptosis. Our findings suggest that extracts of essential oil of C. Heliotropiifolius may be considered as agents to be used therapeutically in treatment of certain cancers.

Anticandidal activity of Croton heliotropiifolius Kunth essential oil is enhanced by N-acetylcysteine and itraconazole.

Aim: Evaluate the anticandidal effect of Croton heliotropiifolius Kunth essential oil and its interaction with azoles and N-acetylcysteine (NAC) against planktonic cells and biofilms. Materials & methods: Broth microdilution and checkerboard methods were used to evaluate the individual and combined activity with fluconazole and itraconazole (ITRA). The antibiofilm effect of the oil was assessed in 96-well plates alone and combined with ITRA and NAC, and cytotoxicity determined by MTT. Results: The oil inhibited all Candida species growth. The activity was enhanced when associated with ITRA and NAC for planktonic cells and biofilms in formation. The effective concentrations were lower than the toxic ones to V79 cells. Conclusion: C. heliotropiifolius Kunth essential oil is an anticandidal alternative, and can be associated with ITRA and NAC.

Candida is a type of fungus that can cause disease in people. In recent years, the number of available drugs to treat this disease have declined. It is important to search for new drugs. Plants are often used to improve health, so we tested the essential oil of a plant called Croton heliotropiifolius to see if it could kill the fungus. We found that the essential oil could kill the fungus, and could be used with other drugs to improve their effects.

Antifungal activity of propafenone on Candida spp. strains: interaction with antifungals and possible mechanism of action.

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.

Evaluation of amlodipine against strains of Candida spp. in planktonic cells, developing biofilms and mature biofilms.

Aim: To evaluate the antifungal activity of amlodipine against strains of Candida spp. and to its possible mechanism of action.Methods: Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results: Amlodipine showed MICs ranging from 62.5 to 250 µg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion: Amlodipine had good antifungal activity against planktonic cells and biofilms of Candida spp., by leading the cells to apoptosis.

Candida is a type of fungus that can cause diseases. This fungus became stronger over time and drugs can no longer kill them easily, so it is important to find new drugs. We decided to study whether amlodipine, a drug used for heart disease, has action against Candida. We discovered that amlodipine make fungi weaker. We still need to do more studies to find out if amlodipine can help prevent Candida diseases.

Analysis of the anti-Candida activity of tricyclic antidepressants in association with amphotericin B and their antifungal mechanisms.

Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128 µg/mL, NOR from 8 to 128 µg/mL, and CLO from 8 to 64 µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.

Phenolic content and antioxidant and antiacetylcholinesterase properties of honeys from different floral origins.

Twenty-three honey samples of Apis mellifera L. forged on plants from northeastern Brazil were analyzed to determine total phenolic content, flavonoid content, antioxidant activity, and antiacetylcholinesterase activity. The total phenol content was determined by using the Folin-Ciocalteu method, and the flavonoid content was analyzed using by the aluminum chloride method. The antioxidant activity was evaluated using the diphenyl-1-picrylhydrazyl-scavenging test. Honey samples from Lippia sidoides Cham. (mean [±standard deviation] 50% inhibitory concentration [IC(50)], 4.20±1.07 mg/mL) and Myracrodruon urundeuva Fr. All. (IC(50), 28.27±1.41 mg/mL) showed better antioxidant activity and presented higher total phenol values (108.50±3.52 mg gallic acid equivalents/100 g for L. sidoides and 68.55±1.01 mg gallic acid equivalents/100 g for M. urundeuva). Several honey samples had relevant results on antiacetylcholinesterase assay. The biological activity of honeys is related to their floral origin, and medicinal plants constitute a useful resource for the generation of functional foods.