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Multitarget Amaranth Peptides: ACE Inhibition, ACE2 Modulation, and Bioavailability Assessment.

Agustina E Nardo1,2, Santiago E Suárez1,2, Susan F García Fillería1,3

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Summary
This summary is machine-generated.

Two amaranth peptides, SFNLPILR and FNLPILR, show potential for lowering hypertension by inhibiting angiotensin-converting enzyme (ACE) and crossing the intestinal barrier. These findings support their development as functional foods for cardiovascular health.

Keywords:
AmaranthAntihypertensive peptidesMultitarget peptidesRenin-angiotensin system

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Area of Science:

  • Biochemistry
  • Cardiovascular Science
  • Food Science

Background:

  • Hypertension is a primary risk factor for cardiovascular disease, significantly influenced by the renin-angiotensin system (RAS).
  • Amaranth-derived peptides have been previously identified as potential renin inhibitors.
  • Understanding the multitarget effects of these peptides is crucial for developing novel antihypertensive strategies.

Purpose of the Study:

  • To evaluate the multitarget potential of three amaranth-derived peptides (SFNLPILR, FNLPILR, AFEDGFEWVSFK) beyond their known renin inhibitory activity.
  • To assess their capacity to inhibit angiotensin-converting enzyme (ACE), modulate ACE2 activity, and determine their bioavailability.
  • To explore their potential as functional food ingredients for hypertension management.

Main Methods:

  • In vitro enzymatic assays to determine ACE and ACE2 inhibitory activity.
  • Bioinformatic analysis to identify bioactive motifs within the peptide sequences.
  • Molecular docking simulations to visualize peptide-ACE interactions.
  • Caco-2 cell monolayer assays to assess intestinal barrier permeability.

Main Results:

  • SFNLPILR and FNLPILR demonstrated potent inhibition of ACE (IC50 = 0.075 and 0.055 mM, respectively).
  • These peptides exhibited selective or minimal modulation of ACE2 enzymatic activity.
  • Bioinformatic and molecular docking analyses confirmed ACE-inhibitory motifs and interactions with catalytic residues.
  • Transepithelial transport studies confirmed the ability of peptide fragments to permeate the intestinal barrier.

Conclusions:

  • SFNLPILR and FNLPILR are effective multifunctional inhibitors of the renin-angiotensin system, targeting ACE.
  • Their ability to cross the intestinal barrier suggests good bioavailability for oral administration.
  • These peptides represent promising candidates for developing functional foods to mitigate hypertension risk through RAS modulation.