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

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.