Targeting FGL2, a molecular drug target for glioblastoma, with natural compounds through virtual screening method.

Background: Fibroleukin-2 protein (FGL2) causes redevelopment of brain tumors. Inhibition of these proteins has shown to improve glioblastoma prognosis and treatment efficacy. Aim: The current study gathered recently exploited natural compounds that suppress glioblastoma proliferation in vitro, tested against FGL2 protein. Method: Twenty-five compounds were explored through a virtual screening platform. Results: Three natural compounds (betanine, hesperetin and ovatodiolide) hit the active site of FGL2. Furthermore, the influence of these compounds was also assessed using in silico gene expression, and ADMET tools showed downregulation of some genes, which caused rapid tumor development while possessing a moderate acute toxicity and pharmacokinetic profile. Conclusion: Our study presents three compounds that are good candidates for evaluation in FGL2 mutated glioblastoma animal models.

Characterization of the profile and concentration of betacyanin in the gastric content, blood and urine of rats after an intragastric administration of fermented red beet juice.

The aim of the study was to evaluate the profile and level of betacyanins in the gastric content, blood (portal and main veins) and urine of rats after an intragastric administration of fermented red beet juice with various betacyanin doses. Samples were collected within 2 h after juice administration into the stomachs, separated from the digestive tract of a living rat. In the gastric content, betacyanins administered underwent intensive degradation and changes in their profile, as a result of the conditions prevailing in the stomach and the intensity of the absorption process. Detection of 19 betacyanins (8 native compounds and 11 metabolites) in rats' physiological fluids with the HPLC-MS/MS method proves betacyanin absorption from the stomach. In addition, the study results suggest that betacyanin dose affects the rate and extent of betacyanin degradation in the gastric content, as well as the intensity of absorption, metabolism and excretion of these pigments.

The impact of the matrix of red beet products and interindividual variability on betacyanins bioavailability in humans.

The influence of the matrix of red beetroot products and interindividual variability on betacyanins bioavailability in humans was studied. In a randomized crossover study 12 volunteers consumed red beet juice and crunchy slices containing betanin and isobetanin. Betalains were analyzed by the HPLC-DAD-MS. Urine samples examined after the consumption of both products contained not only native betacyanins but also their aglycones. In case of juice, the highest betacyanins urine excretion rate was observed within the first 2 h (64 nmol/h), while in case of crunchy slices within the period of 2-4 h (66 nmol/h). Among volunteers, the average total betacyanins excretion rate ranged from 18.54 to 67.96 nmol/h and, 13.15 to 63.58 nmol/h for red beet juice and crunchy slices, respectively. In total, approximately 0.3% of betacyanins (ranging from 0.12 to 0.58%) ingested from both products was excreted. The study showed that betacyanins bioavailability from juice and crunchy slices is similar, with the matrix of products consumed having an impact on betacyanins excretion profile, and the phenotype of volunteers affecting betacyanins excretion rate.

Improvement in the stability of betanin by liposomal nanocarriers: Its application in gummy candy as a food model.

Betanin is a red food pigment with health beneficial effects. Despite interest in the use of betanin, low bioaccessibility and oxidation limit its application. To overcome these restrictions, the betanin was loaded in liposomal nanocarriers with the encapsulation efficiency of 80.35 ±â€¯1%. To assess the efficiency of these nanocarriers, gummy candy was selected as a food model and its nutritional properties such as betanin stability and antioxidant activity were probed. The results showed that the betanin content and antioxidant activity of samples containing betanin-nanoliposomes were at least twice to those of samples containing free betanin. The tests show no differences in the sensory parameters of panelists for gummy candies fortified by betanin-loaded nanoliposomes compared to those fortified by betanin alone. As a result, the liposomal nanoparticles may be introduced as a suitable platform to stabilize and increase the bioavailability of betanin for applications in nutraceutical and medical fields.

The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans.

PURPOSE: To evaluate the plasma bioavailability of betanin and nitric oxide (NOx) after consuming beetroot juice (BTJ) and whole beetroot (BF). BTJ and BF were also analysed for antioxidant capacity, polyphenol content (TPC) and betalain content. METHODS: Ten healthy males consumed either 250 ml of BTJ, 300 g of BF or a placebo drink, in a randomised, crossover design. Venous plasma samples were collected pre (baseline), 1, 2, 3, 5 and 8 h post-ingestion. Betanin content in BTJ, BF and plasma was analysed with reverse-phase high-performance liquid chromatography (HPLC) and mass spectrometry detection (LCMS). Antioxidant capacity was estimated using the Trolox equivalent antioxidant capacity (TEAC) and polyphenol content using Folin-Ciocalteu colorimetric methods [gallic acid equivalents (GAE)] and betalain content spectrophotometrically. RESULTS: TEAC was 11.4 ± 0.2 mmol/L for BTJ and 3.4 ± 0.4 µmol/g for BF. Both BTJ and BF contained a number of polyphenols (1606.9 ± 151 mg/GAE/L and 1.67 ± 0.1 mg/GAE/g, respectively), betacyanins (68.2 ± 0.4 mg/betanin equivalents/L and 19.6 ± 0.6 mg/betanin equivalents/100 g, respectively) and betaxanthins (41.7 ± 0.7 mg/indicaxanthin equivalents/L and 7.5 ± 0.2 mg/indicaxanthin equivalents/100 g, respectively). Despite high betanin contents in both BTJ (~194 mg) and BF (~66 mg), betanin could not be detected in the plasma at any time point post-ingestion. Plasma NOx was elevated above baseline for 8 h after consuming BTJ and 5 h after BF (P < 0.05). CONCLUSIONS: These data reveal that BTJ and BF are rich in phytonutrients and may provide a useful means of increasing plasma NOx bioavailability. However, betanin, the major betalain in beetroot, showed poor bioavailability in plasma.

In vitro digestion of betalainic foods. Stability and bioaccessibility of betaxanthins and betacyanins and antioxidative potential of food digesta.

Betalains are considered to be bioactive dietary phytochemicals. The stability of betacyanins and betaxanthins from either fresh foods or manufactured products of cactus pear fruit ( Opuntia ficus indica L. Mill. cv. Gialla and Rossa) and red beet ( Beta vulgaris L. ssp. vulgaris) was assessed in a simulated oral, gastric, and small intestinal digestion and compared with the digestive stability of purified pigments. A minor loss of indicaxanthin, at the gastric-like environment only, and a decrease of vulgaxanthin I through all digestion steps were observed, which was not affected by food matrix. In contrast, food matrix prevented decay of betanin and isobetanin at the gastric-like environment. Loss of betacyanins, either purified or food-derived, was observed during the small intestinal phase of digestion. Betalamic acid accumulated after digestive degradation of purified pigments, but not of food betalains. Betaxanthins were wholly soluble in the aqueous (bioaccessible) fraction after ultracentrifugation of the postintestinal (PI) digesta, whereas release of betacyanins from the matrix was incomplete. PI digesta inhibited dose-dependently the oxidation of methyl linoleate in methanol, an effect not correlated with the betalain content. The data suggest that digestive stability controls bioaccessibility of dietary betaxanthins, whereas additional factors, relevant to the food matrix and style of processing, affect betacyanin bioaccessibility.

Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans.

The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile.