The
angiotensin-converting enzyme (ACE) inhibitory peptide LVLPGE
provides outstanding antihypertensive effects in vivo, with a maximum
systolic blood pressure (SBP) drop of 39 mmHg at a dose of 10 mg/kg.
We evaluated the gastrointestinal digestion, transport, and in vivo
antihypertensive effects of LVLPGE at different doses. LVLPGE was
resistant to gastrointestinal enzymes with a stability of 97.8% and
a permeability P
app of (5.09 ± 0.94)
× 10–7 cm/s. LVLPGE was mainly transported
through the Caco-2 cell monolayer by the peptide transporter PepT
1 and passive-mediated transport. LVLPGE at doses of 30 and 50 mg/kg
had a positive antihypertensive effect in vivo; 30 mg/kg had a more
significant effect than 50 mg/kg. After oral administration, the pharmacokinetics
of LVLPGE showed that the C
max was 4.65
ng/mL at 2 min. The blood pressure-lowering effect increased as the
concentration of LVLPGE increased in the plasma of spontaneous hypertensive
rats (SHRs).
Diabetes is a major metabolic disease that requires long-term pharmacotherapy. Bioactive peptides have unique advantages such as higher potency, selectivity, and safety over small molecules and have achieved great success in the treatment of diabetes. We previously isolated a dipeptidyl peptidase-IV (DPP-IV) inhibitory peptide VPLVM with IC 50 = 99.68 μM from the protein hydrolysates of broccoli stems and leaves. Here, we evaluated the interaction with DPP-IV, transport, stability, and in vivo hypoglycemic effects of VPLVM. VPLVM interacted closely and steadily with DPP-IV at S1 and S2 pockets. VPLVM had a good gastrointestinal enzyme resistance and was transported through the Caco-2 cell monolayer via paracellular diffusion and by the PepT1 with a P app of 6.96 × 10 −7 cm/s. VPLVM has a t 1/2 of 12.56 ± 0.41 min in vitro plasma stability. In the oral glucose tolerance test, VPLVM showed an excellent hypoglycemic effect at 30 min after administration. VPLVM has potential as a candidate for the treatment of hyperglycemia.
Broccoli-derived peptides show beneficial metabolic effects, and it is necessary to examine their exact functional sequences. First, peptides from the trypsin hydrolysate of broccoli proteins were isolated and identified using column chromatography and quadrupole time-of-flight mass spectrometry. After that, their functions were verified by oral administration. The results identified two novel peptides as Leu-Pro-Gly-Val-Leu-Pro-Val-Ala (LPGVLPVA) and Tyr-Leu-Tyr-Ser-Pro-Ala-Tyr (YLYSPAY). LPGVLPVA exhibited an ACE IC 50 value of 0.776 ± 0.03 μM and a DPP-IV IC 50 value of 392 ± 24 μM; YLYSPAY showed an ACE IC 50 value of 8.52 ± 0.63 μM and a DPP-IV IC 50 value of 181 ± 4 μM. Administration of the peptides reduced the blood pressure of spontaneously hypertensive rats and reduced blood glucose levels in the oral glucose tolerance test in mice. The results indicated that LPGVLPVA and YLYSPAY could be potential nutritional candidates for hypertensive and diabetic people, especially for those with diabetes associated with hypertension.
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