Antifungal Activity of Phenolic and Polyphenolic Compounds from Different Matrices of Vitis vinifera L. against Human Pathogens.

Phenolic compounds, the most widely distributed class of natural products in the plants, show several biological properties including antifungal activity. Phenolics contained in grapes can be classified in two main groups, flavonoids and non-flavonoids compounds. Variability and yield extraction of phenolic and polyphenolic compounds from different matrices of Vitis vinifera depends of cultivar, climate, soil condition and process technology. Unripe grapes, berry skins and seeds, leaves, canes and stems and not-fermented and fermented pomaces represent large reusable and valuable wastes from agricultural and agro-industrial processes. This review summarizes studies that examine the extraction method, chemical characterization, and antifungal activity of phenolic and polyphenolic compounds from edible and non-edible V. vinifera matrices against human fungal pathogens. In the world, around one billion people have fungal diseases related to skin, nail or hair and around 150 million have systemic diseases caused by fungi. Few studies on antifungal activity of plant extracts have been performed. This review provides useful information for the application of V. vinifera phenolics in the field of antifungals for human use.

Anti-Candida Biofilm Activity of Pterostilbene or Crude Extract from Non-Fermented Grape Pomace Entrapped in Biopolymeric Nanoparticles.

Polymeric nanoparticle-based carriers are promising agents to deliver drugs to cells. Vitis vinifera phenolic compounds are known for their antifungal activity against Candida albicans. The aim of the present study was to investigate the antifungal activity of pterostilbene or crude extracts from non-fermented grape pomace, entrapped in poly(lactic-co-glycolic) acid nanoparticles (NPs), with diameters of 50 and 150 nm, on Candida biofilm. The fluorescent probe coumarin 6 was used to study the uptake of poly(lactic-co-glycolic)acid (PLGA) NPs in planktonic cells and biofilm. The green fluorescent signal of coumarin 6 was observed in Candida biofilm after 24 and 48 hours. Both pterostilbene and crude pomace extract entrapped in NPs exerted a significantly higher anti-biofilm activity compared to their free forms. The entrapment efficiency of both pterostilbene and crude pomace extract in PLGA NPs was ~90%. At 16 µg/mL, pterostilbene loaded in PLGA NPs reduced biofilm formation of 63% and reduced mature biofilm of 50%. Moreover, at 50 µg/mL, the pomace extract loaded in NPs reduced mature biofilm of 37%. These results strongly suggest that PLGA NPs are promising nanodevices for the delivery of antifungal drugs as the crude grape pomace extract, a by-product of white wine making.

Chitosan oligosaccharides affect xanthone and VOC biosynthesis in Hypericum perforatum root cultures and enhance the antifungal activity of root extracts.

KEY MESSAGE: Water-soluble chitosan oligosaccharides (COS) affect xanthone and volatile organic compound content, as well as antifungal activity against human pathogenic fungi of extracts obtained from Hypericum perforatum root cultures. Several studies have demonstrated the elicitor power of chitosan on xanthone biosynthesis in root cultures of H. perforatum. One of the major limitations to the use of chitosan, both for basic and applied research, is the need to use acidified water for solubilization. To overcome this problem, the elicitor effect of water-soluble COS on the biosynthesis of both xanthones and volatile organic compounds (VOCs) was evaluated in the present study. The analysis of xanthones and VOCs was performed by HPLC and GC-MS headspace analysis. The obtained results showed that COS are very effective in enhancing xanthone biosynthesis. With 400 mg L-1 COS, a xanthone content of about 30 mg g-1 DW was obtained. The antifungal activity of extracts obtained with 400 mg L-1 COS was the highest, with MIC50 of 32 µg mL-1 against Candida albicans and 32-64 µg mL-1 against dermatophytes, depending on the microorganism. Histochemical investigations suggested the accumulation of isoprenoids in the secretory ducts of H. perforatum roots. The presence of monoterpenes and sesquiterpenes was confirmed by the headspace analysis. Other volatile hydrocarbons have been identified. The biosynthesis of most VOCs showed significant changes in response to COS, suggesting their involvement in plant-fungus interactions.

Effect of Pasteurization on Flavonoids and Carotenoids in Citrus sinensis (L.) Osbeck cv. 'Cara Cara' and 'Bahia' Juices.

Orange juice is considered an excellent dietary source of several bioactive compounds with beneficial properties for human health. Citrus sinensis Osbeck cv. 'Cara Cara' is a bud mutation originated from 'Washington' navel orange, also known as 'Bahia' navel orange. The ascorbic acid, flavonoid, and carotenoid contents in pasteurized and nonpasteurized Bahia and Cara Cara juices using two LC-MS/MS platforms were investigated. Higher ascorbic acid content was observed in Bahia compared to Cara Cara in both pasteurized and nonpasteurized juices. Total flavanones content as well as hesperidin levels were higher in Cara Cara with respect to Bahia pasteurized juice. Cara Cara was also characterized by a significantly higher and diversified carotenoid content compared to Bahia juice with a mixture of (Z)-isomers of lycopene, all-E-ß-carotene, phytoene, and phytofluene isomers accounting for the highest carotenoid proportion. The exceptionally high carotenoid content of Cara Cara may be particularly interesting for nutritional or functional studies of uncommon carotenes in a citrus food matrix.

Acetic acid acts as an elicitor exerting a chitosan-like effect on xanthone biosynthesis in Hypericum perforatum L. root cultures.

KEY MESSAGE: Acetic acid acts as a signal molecule, strongly enhancing xanthone biosynthesis in Hypericum perforatum root cultures. This activity is specific, as demonstrated by the comparison with other short-chain monocarboxylic acids. We have recently demonstrated that Hypericum perforatum root cultures constitutively produce xanthones at higher levels than the root of the plant and that they respond to chitosan (CHIT) elicitation with a noteworthy increase in xanthone production. In the present study, CHIT was administered to H. perforatum root cultures using three different elicitation protocols, and the increase in xanthone production was evaluated. The best results (550 % xanthone increase) were obtained by subjecting the roots to a single elicitation with 200 mg l(-1) CHIT and maintaining the elicitor in the culture medium for 7 days. To discriminate the effect of CHIT from that of the solvent, control experiments were performed by administering AcOH alone at the same concentration used for CHIT solubilization. Unexpectedly, AcOH caused an increase in xanthone production comparable to that observed in response to CHIT. Feeding experiments with (13)C-labeled AcOH demonstrated that this compound was not incorporated into the xanthone skeleton. Other short-chain monocarboxylic acids (i.e., propionic and butyric acid) have little or no effect on the production of xanthones. These results indicate that AcOH acts as a specific signal molecule, able to greatly enhance xanthone biosynthesis in H. perforatum root cultures.

In vitro antifungal activity of extracts obtained from Hypericum perforatum adventitious roots cultured in a mist bioreactor against planktonic cells and biofilm of Malassezia furfur.

Xanthone-rich extracts from Hypericum perforatum root cultures grown in a Mist Bioreactor as antifungal agents against Malassezia furfur. Extracts of Hypericum perforatum roots grown in a bioreactor showed activity against planktonic cells and biofilm of Malassezia furfur. Dried biomass, obtained from roots grown under controlled conditions in a ROOTec mist bioreactor, has been extracted with solvents of increasing polarity (i.e. chloroform, ethyl acetate and methanol). The methanolic fraction was the richest in xanthones (2.86 ± 0.43 mg g(-1) DW) as revealed by HPLC. The minimal inhibitory concentration of the methanol extract against M. furfur planktonic cells was 16 µg mL(-1). The inhibition percentage of biofilm formation, at a concentration of 16 µg mL(-1), ranged from 14% to 39%. The results show that H. perforatum root extracts could be used as new antifungal agents in the treatment of Malassezia infections.

Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 induce different age-related metabolic profiles revealed by 1H-NMR spectroscopy in urine and feces of mice.

Age-related dysbioses of intestinal microbiota and decline in the overall metabolic homeostasis are frequently found in the elderly. Probiotic supplementation may represent a way to prevent or reduce the senescence-associated metabolic disorders. The present study evaluated the metabolic impact of Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 supplementation in relation to age by analyzing urine and feces metabolic profiles using (1)H-nuclear magnetic resonance spectroscopy and multivariate analysis. Adult (3 mo old) and aged (16 mo old) mice received an oral supplementation of the 2 probiotics (1 × 10(9) colony-forming units/d each) or phosphate buffered saline (control) daily for 30 d. Urine and feces were collected for 48 h before the end of the study. Partial least squares-discriminant analysis showed that the urinary discriminant metabolites for the probiotic treatment included higher dimethylglycine in adult and aged mice, lower sarcosine and nicotinate in adult mice, higher N-methylnicotinamide in adult mice and lower N-methylnicotinamide in aged mice compared with their controls. These results indicate a probiotic-induced modulation of homocysteine and NAD metabolism pathways, which have important implications because these pathways are involved in essential cellular processes that can be altered in senescence. The probiotic supplementation also modified the fecal metabolic profiles, inducing in both adult and aged mice higher 4-hydroxyphenylacetate and lower xylose in treated mice compared with their control mice, whereas valerate was greater in treated adult mice and lower in treated aged mice compared with their controls. The ANOVA simultaneous component analysis on urinary and fecal metabolic profiling showed an age × treatment interaction (P < 0.05), confirming the age-related modulation of the metabolic response to probiotic supplementation. The results suggest that L. acidophilus and B. lactis may prevent or reduce age-related metabolic dysfunction.