Enhanced Lacto-Tri-Peptide Bio-Availability by Co-Ingestion of Macronutrients

Some food-derived peptides possess bioactive properties, and may affect health positively. For example, the C-terminal lacto-tri-peptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Val-Pro-Pro (VPP) (together named here XPP) are described to lower blood pressure. The bioactivity depends on their availability at the site of action. Quantitative trans-organ availability/kinetic measurements will provide more insight in C-terminal tri-peptides behavior in the body. We hypothesize that the composition of the meal will modify their systemic availability. We studied trans-organ XPP fluxes in catheterized pigs (25 kg; n=10) to determine systemic and portal availability, as well as renal and hepatic uptake of a water-based single dose of synthetic XPP and a XPP containing protein matrix (casein hydrolyte, CasH). In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber). Portal availability of synthetic XPP was 0.08 ± 0.01% of intake and increased when a protein matrix was present (respectively 3.1, 1.8 and 83 times for IPP, LPP and VPP). Difference between individual XPP was probably due to release from longer peptides. CasH prolonged portal bioavailability with 18 min (absorption half-life, synthetic XPP: 15 ± 2 min, CasH: 33 ± 3 min, p<0.0001) and increased systemic elimination with 20 min (synthetic XPP: 12 ± 2 min; CasH: 32 ± 3 min, p<0.0001). Subsequent renal and hepatic uptake is about 75% of the portal release. A meal containing CasH, increased portal 1.8 and systemic bioavailability 1.2 times. Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times). We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP

Search for Natural Compounds That Increase Apolipoprotein A-I Transcription in HepG2 Cells:Specific Attention for BRD4 Inhibitors

Although increasing apolipoprotein A-I (apoA-I) might lower the cardiovascular disease risk, knowledge on natural compounds that elevate apoA-I transcription is limited. Therefore, the aim of this study was to discover natural compounds that increase apoA-I transcription in HepG2 cells. Since BRD4 inhibition is known to elevate apoA-I transcription, we focused on natural BRD4 inhibitors. For this, the literature was screened for compounds that might increase apoA-I and or inhibit BRD4. This resulted in list A, (apoA-I increasers with unknown BRD4 inhibitor capacity), list B (known BRD4 inhibitors that increase apoA-I), and list C (BRD4 inhibitors with unknown effect on apoA-I). These compounds were compared with the compounds in two natural compound databases. This resulted in (1) a common substructure (ethyl-benzene) in 60% of selected BRD4-inhibitors, and (2) four compounds that increased ApoA-I: hesperetin, equilenin, 9(S)-HOTrE, and cymarin. Whether these increases are regulated via BRD4 inhibition and the ethyl-benzene structure inhibits BRD4 requires further study

Portal Drained Viscera fluxes of XPP—Effect of a protein matrix.

<p>Post-prandial portal drained viscera (PDV) fluxes after <i>intra-gastric</i> administration of tri-peptide (XPP) mixtures: control salt solution (Control), synthetic XPP’s (XPP), casein hydrolyte rich in XPP (CasH) or spiked CasH (CasH + XPP). A: Isoleucine-proline-proline (IPP). B: Leucine-proline-proline (LPP). C: Valine-proline-proline (VPP). Respective number of observations for Control, XPP, CasH and CasH +XPP are for graph A: n = 6, 9, 8 and 9; graph B: n = 6, 10, 9 and 9; graph C: n = 5, 9, 9 and 9. Values are mean ± SEM. Positive values is net release, negative values is net uptake. Statistics: repeated measures two-way ANOVA, mixed model, planned comparisons. All curves are significantly different from the XPP mixture: effect test mixture p<0.01; effect time p<0.01; interaction p<0.01</p

Composition of test mixtures—Study 1.

<p>¹⁾ Chemical purities of the IPP, LPP, and VPP synthetic products were 93.4, 95.0 and 98.7%, respectively (Bachem, Weil am Rhein, Switzerland).</p><p>²⁾ The given amounts of tri-peptides isoleucine-proline-proline (IPP), leucine-proline-proline (LPP), valine-proline-proline (VPP) in the casein hydrolysate (CasH, Casimax, DSM Food Specialties, Delft, The Netherlands). The casein hydrolysate contained 57% protein with 5.4, 16.5 and 0.3 mg/g protein of LPP, LPP and VPP, respectively.</p><p>³⁾ Total XPP = total amount of IPP, LPP and VPP.</p><p>Composition of test mixtures—Study 1.</p

Systemic levels of XPP peptides—Effect of protein matrix.

<p>Post-prandial arterial concentrations after intra-gastric administration of control salt solution (Control), synthetic XPP’s (XPP), casein hydrolysate rich in XPP (CasH) and spiked CasH (CasH + XPP). A: Isoleucine-proline-proline (IPP). B: Leucine-proline-proline (LPP). C: Valine-proline-proline (VPP). Respective number of observations for Control, XPP, CasH and CasH +XPP are for graph A: n = 9, 10, 9 and 10; graph B: n = 10, 10, 9 and 10; graph C: n = 8, 10, 9 and 10. Values are mean ± SEM. Statistics: repeated measures two-way ANOVA, mixed model, planned comparisons. All curves are significantly different from the XPP mixture: effect test mixture p<0.001; effect time p<0.001; interaction p<0.001.</p

Organ Total Net balances of XPP peptides.

<p>Study 1. Post-prandial total net balances across organs over 90 min experimental period after <i>intra-gastric</i> administration of tri-peptide (XPP) mixtures: a synthetic dose of XPP (XPP), XPP containing casein hydrolyte (CasH) and spiked CasH (CasH + XPP). Organs: portal drained viscera (PDV), Liver, Splanchnic area (SPL), Kidneys. Positive balance is net release by an organ. Negative balance is net uptake by an organ. Values are mean ± SEM. Statistics: unpaired t-test for comparison of net balances of natural occurring XPP vs administrated XPP (Control vs XPP), water-based vs protein matrix (XPP vs CasH), and for comparison protein matrixes with vs without XPP spike (CasH vs CasH+XPP). Hooks: significance p<0.05. dotted hooks: tendency p<0.10.</p

Composition of test meals—Study 2.

<p>¹⁾: Indicated is the amount of protein supplied by the isolates.</p><p>²⁾: CHO: maize starch, sucrose and glucose in the weight ratio 2:1:1.</p><p>³⁾: Fat: soybean oil and sunflower oil in the weight ratio 4:1.</p><p>⁴⁾ The casein hydrolysate product (Casimax, DSM Food Specialties, Delft, The Netherlands) contained 57% protein with 5.4, 16.5 and 0.3 mg/g protein LPP, LPP and VPP, respectively.</p><p>⁵⁾ Fiber: modified citrus pectin.</p><p>Composition of test meals—Study 2.</p

Enhanced Lacto-Tri-Peptide Bio-Availability by Co-Ingestion of Macronutrients

Some food-derived peptides possess bioactive properties, and may affect health positively. For example, the C-terminal lacto-tri-peptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP) and Val-Pro-Pro (VPP) (together named here XPP) are described to lower blood pressure. The bioactivity depends on their availability at the site of action. Quantitative trans-organ availability/kinetic measurements will provide more insight in C-terminal tri-peptides behavior in the body. We hypothesize that the composition of the meal will modify their systemic availability. We studied trans-organ XPP fluxes in catheterized pigs (25 kg; n=10) to determine systemic and portal availability, as well as renal and hepatic uptake of a water-based single dose of synthetic XPP and a XPP containing protein matrix (casein hydrolyte, CasH). In a second experiment (n=10), we compared the CasH-containing protein matrix with a CasH-containing meal matrix and the modifying effects of macronutrients in a meal on the availability (high carbohydrates, low quality protein, high fat, and fiber). Portal availability of synthetic XPP was 0.08 ± 0.01% of intake and increased when a protein matrix was present (respectively 3.1, 1.8 and 83 times for IPP, LPP and VPP). Difference between individual XPP was probably due to release from longer peptides. CasH prolonged portal bioavailability with 18 min (absorption half-life, synthetic XPP: 15 ± 2 min, CasH: 33 ± 3 min, p<0.0001) and increased systemic elimination with 20 min (synthetic XPP: 12 ± 2 min; CasH: 32 ± 3 min, p<0.0001). Subsequent renal and hepatic uptake is about 75% of the portal release. A meal containing CasH, increased portal 1.8 and systemic bioavailability 1.2 times. Low protein quality and fiber increased XPP systemic bioavailability further (respectively 1.5 and 1.4 times). We conclude that the amount and quality of the protein, and the presence of fiber in a meal, are the main factors that increase the systemic bioavailability of food-derived XPP