Oral administration of nasturtium affects peptide YY secretion in male subjects.

SCOPE: Nasturtium plants contain the glucosinolate glucotropaeolin and its corresponding breakdown product benzyl isothiocyanate (BITC), the latter being intensively studied with regard to cancer chemoprevention and anti-inflammatory properties. In addition, recent research has shown that isothiocyanates are able to activate the release of several gut hormones in vitro and in rodent studies. Here, we tested the effects of a dietary nasturtium administration on circulating levels of gut hormones in humans. METHODS AND RESULTS: Metabolically healthy males (n = 15) received a single oral dose of 10 g freeze-dried nasturtium leaf material suspended in water or only water (control). Blood samples were taken every hour and serum concentrations of insulin, C-peptide, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide (PYY) were analyzed. Oral nasturtium intake resulted in an increased release of PYY over a time period of 6 h whereas circulating levels of other hormones were not changed. CONCLUSION: Given the finding that nasturtium consumption enhances secretion of PYY, a key hormone involved in energy regulation, special diets containing nasturtium, or supplementation with nasturtium or BITC might be considered in the treatment of obesity.

Bioavailability and metabolism of benzyl glucosinolate in humans consuming Indian cress (Tropaeolum majus L.).

SCOPE: Benzyl isothiocyanate (BITC), which occurs in Brassicales, has demonstrated chemopreventive potency and cancer treatment properties in cell and animal studies. However, fate of BITC in human body is not comprehensively studied. Therefore, the present human intervention study investigates the metabolism of the glucosinolate (GSL) glucotropaeolin and its corresponding BITC metabolites. Analyzing BITC metabolites in plasma and urine should reveal insights about resorption, metabolism, and excretion. METHODS AND RESULTS: Fifteen healthy men were randomly recruited for a cross-over study and consumed 10 g freeze-dried Indian cress as a liquid preparation containing 1000 µmol glucotropaeolin. Blood and urine samples were taken at several time points and investigated by LC-ESI-MS/MS after sample preparation using SPE. Plasma contained high levels of BITC-glutathione (BITC-GSH), BITC-cysteinylglycine (BITC-CysGly), and BITC-N-acetyl-L-cysteine (BITC-NAC) 1-5 h after ingestion, with BITC-CysGly appearing as the main metabolite. Compared to human plasma, the main urinary metabolites were BITC-NAC and BITC-Cys, determined 4-6 h after ingestion. CONCLUSION: This study confirms that consumption of Indian cress increases the concentration of BITC metabolites in human plasma and urine. The outcome of this human intervention study supports clinical research dealing with GSL-containing innovative food products or pharmaceutical preparations.

The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC.

In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level.

Determination of bioactive, free isothiocyanates from a glucosinolate-containing phytotherapeutic agent: a pilot study with in vitro models and human intervention.

Isothiocyanates (ITCs) derived from plants of the order Brassicales are known for their antibacterial, anti-inflammatory or anticarcinogenic potential. Although only the free ITCs exert bioactivity, quantification in vivo is almost exclusively performed on total ITC/metabolite content. We therefore investigated in a pilot study the amount of free ITC at different steps critical for therapeutic efficacy. A sensitive and specific GC-MS/MS method for the simultaneous quantification of individual free ITC after solid-phase extraction (SPE) was developed. We show here that release of biologically active ITC from plants occurs at not only alkaline but also acidic pH. Furthermore, in human urine conversion of the ultimate, inactive mercapturic acid conjugate back into its corresponding bioactive form is increased at alkaline as compared to neutral pH. This was also observed in the urine of human volunteers, where - in correlation with the pH value - a mean of 0.16 to 1.03 µmol ITC was detected after oral application of a phytotherapeutic agent containing 30.4 µmol of the initial pro-drugs. The amounts of free ITC being necessary for bioactivity in vitro were found to be indeed achieved in vivo. These data might be helpful to better understand the beneficial effects of ITC observed in vivo.