Exploring the Fluconazole-Resistance Modifying Activity and Potential Mechanism of Action of Fixed Oil from Caryocar coriaceum Wittm. (Caryocaraceae) against Candida Species.

The fixed oil from the inner mesocarp of Caryocar coriaceum Wittm. is used in the Chapada do Araripe region of Brazil for the treatment of genitourinary candidiasis. This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of C. coriaceum tested against three Candida yeasts. The oil was characterized by gas chromatography (GC-MS and GC-FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub-inhibitory concentrations (MIC/8). The mechanism of action of C. coriaceum fixed oil was determined by evaluating the inhibition of morphological transition in Candida spp. The chemical composition of the fixed oil of C. coriaceum comprised both unsaturated and saturated fatty acids. Oleic (61 %) and palmitic (33 %) acids were the major constituents. Regarding its anti-Candida activity, the oil inhibited the growth of C. albicans (IC50 : 371 µg/mL) and C. tropicalis (IC50 : 830 µg/mL). Furthermore, the oil reversed the antifungal resistance of C. albicans and C. tropicalis, restoring the susceptibility to fluconazole and reducing their IC50 from 12.33 µg/mL and 362 µg/mL to 0.22 µg/mL and 13.93 µg/mL, respectively. The fixed oil of C. coriaceum completely inhibited the morphological transition of C. albicans and C. tropicalis at a concentration of 512 µg/mL, but exhibited limited low antifungal potential against C. krusei. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the Drosophila melanogaster in vivo model. The fixed oil from the inner mesocarp of C. coriaceum emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by Candida spp.

Caryocar coriaceum fruits as a potential alternative to combat fungal and bacterial infections: In vitro evaluation of methanolic extracts.

Caryocar coriaceum, commonly known as 'pequi', is a medicinal species used traditionally for the herbal treatment of infectious and parasitic diseases in the Brazilian Northeast region. In this study, we investigated whether the fruits of C. coriaceum have bioactive chemical constituents against etiological agents of infectious diseases. The methanolic extract of the internal mesocarp of the fruits of C. coriaceum (MECC) was chemically analyzed and evaluated for its antimicrobial and drug-enhancing activity against multidrug-resistant pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and Candida spp. strains. The extract had flavones, flavonols, xanthones, catechins, and flavanones as major classes. A total of 11.26 mg GAE/g of phenolics, and 5.98 mg QE/g of flavonoids were found. No intrinsic antibacterial activity was observed; however, the extract was able to intensify the action of gentamicin and erythromycin against multi-resistant strains. The anti-Candida effect observed in this study was mainly due to the formation of reactive oxygen species. The extract was capable of causing damage to the plasmatic membrane of Candida tropicalis through pores formation. Our findings partially support the ethnopharmacological uses of the fruit pulp of C. coriaceum against infectious and parasitic diseases.

Traditional Uses, Phytochemistry, and Bioactivities of Mesosphaerum suaveolens (L.) Kuntze.

Mesosphaerum suaveolens (L.) Kuntze is a species widely used traditionally in the treatment of ailments, such as stomach pain, hemorrhoids, cough, verminosis, ulcer, liver disease, fever, influenza, nasal congestion, and inflammation. This review aims to provide a survey of available information on seven international electronic databases (Google Scholar, Medline, ResearchGate, Web of Science, Scopus, Science Direct, and PubMed) about botanical aspects, traditional uses, phytochemistry, and biological activities of M. suaveolens. Mesosphaerum suaveolens is a tropical America native species, but it can be found in several parts of the world as a ruderal plant. The species is the most studied species of the genus Lamiaceae due its phytochemical aspect, especially regarding the chemical composition of its essential oil. Besides the essential oils, M. suaveolens is a source of numerous secondary compounds such as triterpenes, diterpenes, and phenolic compounds, which are related to its biological activities, such as allelopathic, antibacterial, antifungal, insecticidal, and larvicidal activities as described in the literature.

Antibacterial and modulatory activities of ß-cyclodextrin complexed with (+)-ß-citronellol against multidrug-resistant strains.

The present study aimed to investigate the antibacterial and modulatory activities of (+)-ß-citronellol (ßCT), ß-cyclodextrin (ß-CD), and their complex ßCT/ß-CD and characterize them using infrared spectroscopy. Infrared spectra were recorded in the 750-4000 cm-1 region. The antibacterial effects of these compounds and their modulatory-antibiotic activities were determined using the minimum inhibitory concentration (MIC) test. Signatures of these pure compounds were detected in the infrared spectrum of the ßCT/ß-CD complex. The MIC of the ßCT/ß-CD complex against the tested strains was found to be 1024 µg/mL. The antagonistic and synergistic effects of these compounds were also observed using the modulation tests. ßCT or ß-CD alone did not exhibit any direct antibacterial activity. However, the ßCT/ß-CD complex in combination with gentamicin showed a synergistic effect against E. coli.

Effect of α-Bisabolol and Its ß-Cyclodextrin Complex as TetK and NorA Efflux Pump Inhibitors in Staphylococcus aureus Strains.

Efflux pumps are proteins present in the plasma membrane of bacteria, which transport antibiotics and other compounds into the extracellular medium, conferring resistance. The discovery of natural efflux pump inhibitors is a promising alternative. α-Bisabolol is a sesquiterpene isolated from several plants such as Matricaria chamomilla L. and has important properties such as antibacterial and anti-inflammatory activity. Currently, the formation of inclusion complexes with ß-Cyclodextrin has been used for improving the physicochemical characteristics of the host molecule. This study evaluated the effect of α-Bisabolol, in isolation and in complexation with ß-Cyclodextrin, as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) was determined. Subsequently, inhibitory activity over the pumps was observed by an MIC reduction for the antibiotics, by using subinhibitory concentrations (MIC/8) in combination with tetracycline and norfloxacin. The MIC of the compounds was ≥1024 µg/mL. α-Bisabolol potentiated the action of tetracycline and reduced the MIC of norfloxacin to a clinically relevant concentration. The complexed substance showed synergism however, the effect of the isolated α-Bisabolol was superior to the complex. These results indicate α-Bisabolol is a potential substance to be used as an efflux pump inhibitor.

UPLC-MS-ESI-QTOF Analysis and Antifungal Activity of the Spondias tuberosa Arruda Leaf and Root Hydroalcoholic Extracts.

The aim of this study was to identify and evaluate the chemical compositions and effects of the S. tuberosa leaf and root hydroalcoholic extracts (HELST and HERST) against different strains of Candida. Chemical analysis was performed by Ultra-Performance Liquid Chromatography Coupled to Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF). The Inhibitory Concentration of 50% of the growth (IC50) as well as the intrinsic and combined action of the extracts with the antifungal fluconazole (FCZ) were determined by the microdilution method while the minimum fungicidal concentrations (MFCs) and the effect on fungal morphological transitions were analyzed by subculture and in humid chambers, respectively. From the preliminary phytochemical analysis, the phenols and flavonoids were the most abundant. The intrinsic IC50 values for HELST ranged from 5716.3 to 7805.8 µg/mL and from 6175.4 to 51070.9 µg/mL for the HERST, whereas the combination of the extracts with fluconazole presented IC50 values from 2.65 to 278.41 µg/mL. The MFC of the extracts, individually, for all the tested strains was ≥16384 µg/mL. When fluconazole was combined with each extract, the MFC against CA URM 5974 was reduced (HELST: 2048 and HERST: 4096 µg/mL). Synergism was observed against standard C. albicans (CA) and C. tropicalis (CT) strains and with the root extract against the CT isolate. The leaf extract inhibited the morphological transition of all strains while the root extract inhibited only CT strains.