Purpose: Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has cancer chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects the metabolite profile of curcumin. Methods

Recent data concerning the effect of soybean 7S globulin subunits on the upregulation of LDL receptors in Hep G2 cells identified the alpha' subunit as the candidate responsible for this biological effect. In vivo evaluation of this subunit on cholesterol homeostasis was hampered by the lack of suitable amounts of alpha' chain. A novel separation procedure allowed us to investigate the effects of alpha' subunit administration on plasma cholesterol and triglyceride levels, as well as on the activity of liver beta-VLDL receptors of rats fed a hypercholesterolemic (HC) diet. Rats were divided into 9 groups fed the following diets for 28 d: standard diet; HC diet; HC diets + 5, 10, and 20 mg/(kg body weight. d) of alpha' subunit; HC diets + 50, 100, and 200 mg/(kg body weight. d) of soybean 7S globulin; HC diet + 200 mg/(kg body weight. d) clofibrate. The highest dose of the alpha' subunit decreased plasma cholesterol and triglycerides 36 and 34%, respectively, in rats fed the HC diet; 10-fold amounts clofibrate reduced plasma cholesterol and triglycerides 38 and 41%. The activity of liver beta-VLDL receptors of rats fed the HC diet with the highest dose of the alpha' subunit had a 96% increase in binding compared with the HC diet group, thus restoring the receptor activity to that of rats fed the standard diet. These results represent the first in vivo evidence of both the plasma lipid-lowering properties and the upregulation of liver beta-VLDL receptors induced by the soybean alpha' subunit.

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Glucosinolates (GLs), natural compounds extracted from Brassicaceae and precursors of isothiocyanates (ITCs), have been studied in the last decades mostly due to their chemopreventive activity and, more recently, for their potential use as novel chemotherapeutics. The aim of the present study was to investigate the in vitro and in vivo activity of glucomoringin (GMG), an uncommon member of the GLs family, and to compare it with glucoraphanin (GRA), one of the most studied GL. We have evaluated the potency of both compounds in inducing cell death, cell cycle perturbations, apoptosis, NF-kB inhibition and GST-pi activity in human carcinoma cells with different GST-pi contents as well as in human multiple myeloma and leukaemia cell lines. GMG-derived ITC (GMG-ITC) showed to be more effective compared to GRA-derived ITC (Sulforaphane), especially in inhibiting NF-kB activity and inducing apoptosis through a caspase-dependent pathway; these effects were more pronounced in myeloma cells, in which we could also observe a long lasting growth inhibitory effect, probably due to NF-kB inhibition, which is considered essential for myeloma cell survival. Both GLs were able to induce cell death in the muM range in all tested cell lines but caused cell cycle perturbations only in myeloma cells; they were also able to modulate the GST/GSH pathway by causing a 3-fold increase in GST-pi activity in MCF7 cells. In vivo study showed that pure GMG-ITC was only slightly active in a carcinoma mice model, whereas it had significant antitumoral activity in a myeloma model, causing little toxicity.

BackgroundThe aim of this study was to evaluate the performance of Edmonton Frail Scale (EFS) on frailty assessment in association with multi-dimensional conditions assessed with specific screening tools and to explore the prevalence of frailty by gender.MethodsWe enrolled 366 hospitalised patients (women\men: 251\115), mean age 81.5 years. The EFS was given to the patients to evaluate their frailty. Then we collected data concerning cognitive status through Mini-Mental State Examination (MMSE), health status (evaluated with the number of diseases), functional independence (Barthel Index and Activities Daily Living; BI, ADL, IADL), use of drugs (counting of drugs taken every day), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS), Skeletal Muscle Index of sarcopenia (SMI), osteoporosis and functionality (Handgrip strength).ResultsAccording with the EFS, the 19.7% of subjects were classified as non frail, 66.4% as apparently vulnerable and 13.9% with severe frailty.The EFS scores were associated with cognition (MMSE: β = 0.980; p < 0.01), functional independence (ADL: β = −0.512; p < 0.00); (IADL: β = −0.338; p < 0.01); use of medications (β = 0.110; p < 0.01); nutrition (MNA: β = −0.413; p < 0.01); mood (GDS: β = −0.324; p < 0.01); functional performance (Handgrip: β = −0.114, p < 0.01) (BI: β = −0.037; p < 0.01), but not with number of comorbidities (β = 0.108; p = 0.052). In osteoporotic patients versus not-osteoporotic patients the mean EFS score did not differ between groups (women: p = 0.365; men: p = 0.088), whereas in Sarcopenic versus not-Sarcopenic patients, there was a significant differences in women: p < 0.05.ConclusionsThis study suggests that measuring frailty with EFS is helpful and performance tool for stratifying the state of fragility in a group of institutionalized elderly. As matter of facts the EFS has been shown to be associated with several geriatric conditions such independence, drugs assumption, mood, mental, functional and nutritional status.

These results support the view that hyperforin plays a key role in the antidepressant-like activity of Hypericum p. However, brain concentrations after effective doses are probably far from those active in vitro on the neurotransmitter mechanisms so far investigated.

The hydroalcoholic extract of Hypericum perforatum L. is an effective antidepressant, although its mechanism of action is still unknown. It inhibits the synaptosomal uptake of serotonin (5-HT), dopamine and noradrenaline, suggesting a biochemical mechanism similar to the synthetic standard antidepressants. In the present study, further investigating this hypothesis, we confirmed that a hydromethanolic extract of H. perforatum inhibited [3H]5-HT accumulation in rat brain cortical synaptosomes with an IC50 value of 7.9 microg/ml. The IC50 of pure hyperforin was 1.8 microg/ml, so the activity of the total extract is not related only to its hyperforin content (<5%). This inhibitory effect, however, is not due to a direct interaction with, and blockade of, the 5-HT transporters since the extract, like hyperforin, did not inhibit [3H]citalopram binding (IC50 > 100 microg/ml and 10 microg/ml, respectively). We also found that 3-10 microg/ml of the extract, or 0.3-1 microg/ml hyperforin, induced marked tritium release from superfused synaptosomes previously loaded with [3H]5-HT. The releasing effect of the extract resembles the releasing effect of a reserpine-like compound (Ro 04-1284), i.e. it was slightly delayed and was 5-HT carrier- and calcium-independent. These data suggest that the hydromethanolic extract of H. peforatum, similarly to Ro 04-1284, rapidly depletes storage vesicles, raising the cytoplasmic concentration of 5-HT, and this increase is presumably responsible for the apparent inhibition of [3H]5-HT uptake. Therefore, our in vitro data do not confirm that the hydromethanolic extract of H. perforatum acts as a classical 5-HT uptake inhibitor but indicate reserpine-like properties. However, the concentrations of the active component(s) effective in vitro as reserpine-like agent(s) (i.e. corresponding to > or =3 microg/ml of the hydromethanolic extract) do not seem to be achieved in the brain after pharmacologically effective doses of the extract, as indicated by the finding that there were no significant changes of rat brain 5-HT and 5-hydroxyindoleacetic acid levels after a schedule of treatment (3 x 300 mg/kgday, orally) active in an animal model predictive of antidepressant-like activity. These data also suggest that the antidepressant effect of H. perforatum extracts is unlikely to be associated with interaction with GABA, benzodiazepine and 5-HT1 receptors since, in receptor binding studies, we found IC50 values higher than 5 microg/ml. Therefore other, still unknown, mechanisms are possibly involved in H. perforatum antidepressant effects.