Resumo

Introduction: Uncaria tomentosa is a vine widely distributed in the South America rainforest. Phytochemically, cat's claw bark have been studied intensively but there are few studies focusing on its phenolic compounds. Nonetheless, it is known that the polyphenolic fraction is composed mainly by phenolic acids, flavonoids monomers and high molecular weight proanthocyanidins, including condensed tannins derived from epicatechin and catechin. Former works reported relevant biological activities for cat’s claw bark, for instance, antiproliferative, immunostimulatory, anti-inflammatory, antiviral, and antioxidant. However, there is no previous report on the antifungal activity of crude extracts or any purified fraction prepared from it. Paradoxical effect refers the situation whereby increasing doses of medication reverses its own activity, to the point that an almost absolute inactivity could be reached. In the practice a turbid growth is still noticeable with rather high drug concentrations above the minimum inhibitory concentration. This effect was also reported to caspofungin, an echinocandin derivative used for the treatment of invasive candidiasis. Objective: This work addresses the paradoxical effect of high molecular weight polyphenol fraction from U. tomentosa on a C. parapsilosis resistant strain(CP03). Materials and Methods: Bark samples purchased in Brazilian mark were properly air-dried and comminuted. The enriched fraction, PP2, was obtained from a hydroethanolic crude extract prepared specifically for that intend. The total polyphenols content was estimated by the Folin Ciocalteau assay. For testing antifungal screening, the determination of minimum inhibitory concentration (MIC) was performed in accordance with the M27-A3 guidelines of CLSI. Results and Discussion: The PP2 total polyphenols content was 3.7 µg/mg. Corroborating previous finding, PP2 exhibit a moderate antifungal activity (3,90 µg/mL). In that occasion, however, the resistance to growth inhibition and killing of C. parapsilosis clinical isolates could be assessed at PP2 high concentrations (500 - 62,5 µg/mL). This behavior resembles closely that noticed for caspofungin. This newly introduced agent has as its mechanism of action non-competitive inhibition of synthesis of (1,3)-β-D-glucan, a principal constituent of fungal cell walls. Conclusion: An noticeable paradoxical effect on the C. parapsilosis strain growth was elicited by PP2, a purified fraction of high molecular weight polyphenols from U. tomentosa bark. Further studies are in progress to better enlighten this finding.