Franco Ferrari

1H NMR spectra of normal urines: reference ranges of the major metabolites.

Serial urine samples from 50 normal subjects were studied by 1H NMR spectroscopy operating at 300 MHz. Analyses of the spectra have shown the presence of the following metabolites in 100% of the normal subjects: Creatinine, lactate, alanine, citrate, dimethylamine, trimethylamine-N-oxide, glycine and hippurate. Other analytes, such as creatine, valine, betaine, leucine and isoleucine, were sometimes found. All metabolites were quantified on the basis of peak heights and were expressed as mmol/mol of creatinine. The study of metabolic profiles in serial samples allowed us to evaluate intra-individual variability and physiological changes due to feeding. The aim of our report is to define standard conditions for this analytical technique and to calculate confidence intervals for the major metabolites in normal urine samples, such as preliminary and mandatory stages for clinical diagnostic 1H NMR utilization.

Chemical and Pharmacological Studies of Phyllanthus caroliniensis in Mice

The aim of this study was to isolate and characterize the constituents of the hydroalcoholic extract (HE) of the leaves, stems and roots from P. caroliniensis, and also to evaluate the preliminary antinociceptive action of the HE and purified compounds in mice.

Influence of feeding on metabolite excretion evidenced by urine 1H NMR spectral profiles : a comparison between subjects living in Rome and subjects living at arctic latitudes (Svaldbard)

Urines from 25 normal subjects living in Rome and 25 normal subjects living in Ny-Alesund (Svaldbard) were analysed by 1HNMR spectroscopy. The observed differences in the concentration of the major metabolites were correlated to the composition of the diet. It was found that a diet rich of carbohydrates, such as the Italian diet, is responsible for an increased excretion of citrate, lactate, alanine, and glycine. Thus, a correct diagnostical interpretation of urinary metabolites needs to consider feeding habits.

Anthocyanins and xanthones in the calli and regenerated shoots of Hypericum perforatum var. angustifolium (sin. Fröhlich) Borkh.

The present paper reports on the production of anthocyanins and xanthones in different in vitro systems of Hypericum perforatum var. angustifolium (sin. Fröhlich) Borkh. Undifferentiated calli and regenerated shoots at different developmental stages were analyzed by applying an extractive and an analytical procedure capable of detecting and quantifying anthocyanins. The findings revealed, for the first time, the co-presence of hypericins and anthocyanins in shoots at initial and more developed stages of H. perforatum var. angustifolium L. Moreover, a high production of xanthones was found in the undifferentiated calli.

Flavanones and xanthones from Maclura pomifera

Abstract (+-)Euchrestaflavanones B and C and 8-prenyltoxyloxanthone C have been isolated from the root bark of Maclura pomifera . A study of the cyclization of alvaxanthone under varying conditions is reported.

Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (PtpB) Inhibitors from Natural Products

Protein tyrosine phosphatase B (PtpB) is one of the virulence factors secreted into the host cell by Mycobacterium tuberculosis. PtpB attenuates host immune defenses by interfering with signal transduction pathways in macrophages and, therefore, it is considered a promising target for the development of novel anti-tuberculosis drugs. Here we report the discovery of natural compound inhibitors of PtpB among an in house library of more than 800 natural substances by means of a multidisciplinary approach, mixing in silico screening with enzymatic and kinetics studies and MS assays. Six natural compounds proved to inhibit PtpB at low micromolar concentrations (< 30 µM) with Kuwanol E being the most potent with K i = 1.6 ± 0.1 µM. To the best of our knowledge, Kuwanol E is the most potent natural compound PtpB inhibitor reported so far, as well as it is the first non-peptidic PtpB inhibitor discovered from natural sources. Compounds herein identified may inspire the design of novel specific PtpB inhibitors.

Chitosan enhances xanthone production in Hypericum perforatum subsp. angustifolium cell cultures

Hypericum perforatum is an important medicinal plant containing numerous biologically active compounds. The effect of chitosan elicitation on xanthone biosynthesis in calli and in cell suspension cultures of H. perforatum subsp. angustifolium was evaluated. Elicited cell cultures showed an increase in xanthone production and a simultaneous decrease in flavonoid production. Chitosan also induced the production of 1,7-dihydroxyxanthone (euxanthone) and cadensin G, which were not detected in either the calli nor the non-elicited cell cultures. 1,7-Dihydroxyxanthone was in part (21%) released in the culture medium.

Chemical composition and antifungal activity of Hypericum perforatum subsp. angustifolium roots from wild plants and plants grown under controlled conditions

The medicinal properties of the aerial parts of Hypericum perforatum subsp. angustifolium have been extensively investigated, yet little is known about the chemical composition or potential uses of the root extracts. In this study, xanthone production in wild plants and plants grown under controlled conditions was investigated. Chemical analyses carried out on wild plants revealed that xanthones were mainly accumulated in the roots. We mainly detected 1,7-dihydroxyxanthone, paxanthone, 5-O-methyl-2-deprenylrheediaxanthone B, kielcorin. The roots of wild plants showed low xanthone accumulation. In the roots of plants grown under controlled conditions, xanthone accumulation was 27 times greater than that in the roots of wild-grown plants. Kielcorin was not detected in the roots of plants grown under controlled conditions. As xanthones are known for their antifungal activity, the extracts from both samples were tested against the human fungal pathogens Candida albicans, non-albicansCandida species, Cryptococcus neoformans, and dermatophytes. The root extracts from plants grown under controlled conditions showed greater antifungal activity, probably correlated with higher xanthone accumulation.

Xanthones from calli of Hypericum Perforatum subsp. Perforatum

Two new xanthone derivatives, 1-hydroxy-5,6,7-trimethoxyxanthone and 3-O-methylpaxanthone were isolated from callus of Hypericum perforatum subsp. perforatum together with the known paxanthone, cadensin G, 1-hydroxy-6,7-dimethoxyxanthone, 1,3,6,7-tetrahydroxyxanthone, and 1,3,5,6-tetrahydroxyxanthone. The structures of the new compounds were established by spectroscopic methods.

Three New Diels-Alder Type Adducts from the Roots of Sorocea bonplandii Baillon

Three new ketalized Diels-Alder type adducts named soroceal (1), sorocein A (2), sorocein B (3), were isolated from the methanolic extract of the roots of Sorocea bonplandii. The structures were assigned on the basis of chemical and spectroscopic evidences