Renata Cougo Moraes

In vitro evaluation of the acquisition of resistance, antifungal activity and synergism of Brazilian red propolis with antifungal drugs on Candida spp.

To evaluate the ability of Candida parapsilosis and Candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from Brazilian red propolis (BZP‐BRP) as compared to fluconazole (FLC). To investigate possible synergy between BZP‐BRP and FLC and anidulafungin (AND).

Bioactive soy isoflavones: extraction and purification procedures, potential dermal use and nanotechnology-based delivery systems

Isoflavones are polyphenol compounds found mainly in legumes such as soybeans (Glycine max (L.) Merrill). These compounds can be found in different chemical forms; however, the beneficial effects for skin care have been mainly credited to their free forms. This manuscript claims to review the main effects of isoflavone aglycones on the skin, the different techniques for obtaining bioactive forms from soybeans, and the interest in incorporating them into topical systems. The benefits of dermatological application of isoflavones, as anti-aging action, estrogenic activity, wound healing properties, and antiphotocarcinogenic effects are highlighted. Moreover, the advantages and drawbacks of the extraction techniques of soybeans, methods for converting glucosides into aglycones, and purification procedures are described. Different strategies to incorporate these poorly soluble compounds in conventional or nanostructured delivery systems are also discussed. Illustrative examples especially for genistein-loaded liposomes, nanoemulsions, nanocapsules and cyclodextrin complexation are reported.

Cat's claw oxindole alkaloid isomerization induced by common extraction methods

Cat’s claw oxindole alkaloids are prone to isomerization in aqueous solution. However, studies on their behavior in extraction processes are scarce. This paper addressed the issue by considering five commonly used extraction processes. Unlike dynamic maceration (DM) and ultrasound-assisted extraction, substantial isomerization was induced by static maceration, turbo-extraction and reflux extraction. After heating under reflux in DM, the kinetic order of isomerization was established and equations were fitted successfully using a four-parameter Weibull model (R2 > 0.999). Different isomerization rates and equilibrium constants were verified, revealing a possible matrix effect on alkaloid isomerization.

Catʼs Claw Oxindole Alkaloid Isomerization Induced by Cell Incubation and Cytotoxic Activity against T24 and RT4 Human Bladder Cancer Cell Lines

The antitumor activity of Uncaria tomentosa, a native vine from the Amazonian rainforest, has been ascribed to pentacyclic oxindole alkaloids occurring in its bark. Former studies have shown that this activity, as well as its intensity, depends on whether cats claw alkaloids occur as original compounds or isomerized derivatives. This work addresses this aspect, using T24 and RT4 human bladder cancer cell lines for that purpose. Bark samples were extracted by dynamic maceration, prepurified with cross-linked polyvinylpyrrolidone and properly fractioned by an ion exchange process to obtain an oxindole alkaloid purified fraction. Alkaloid isomerization was induced by heating it under reflux at 85 °C. Samples collected after 5, 15, and 45 min of heating were analyzed by HPLC-PDA, freeze-dried at once, and separately assayed using the non-isomerized purified fraction for comparison purposes. The latter showed significant and dose-dependent cytotoxic activity against both T24 and RT4 cancer cell lines (IC50: 164.13 and 137.23 µg/mL, respectively). However, results for both cell lines were equivalent to those observed for isomerized samples (p > 0.05). The alkaloid isomerization induced by the incubation conditions (buffered medium pH 7.4 and temperature 37 °C) helps to explain the similar results obtained from non-isomerized and isomerized samples. Mitraphylline, speciophylline, uncarine F, and, to a lesser degree, pteropodine were more susceptible to isomerization under the incubation conditions. Thus, the alkaloid profile of all fractions and their cytotoxic activities against T24 and RT4 human bladder cancer cell lines are determined to a large extent by the incubation conditions.

In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates

Abstract Context: Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance. Objectives: The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated. Materials and methods: TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis. Results: The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0 μg/mL) and WIF and FLZ (1.95:8.0 μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700–800 cm−1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF. Conclusions: DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat’s claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.