Lactoferrin-Derived Peptides Lower Blood Pressure by Blocking Angiotensin Receptors | Research

The takeaway

Peptides derived from lactoferrin selectively block angiotensin AT1 receptors, inhibiting blood vessel constriction through a mechanism distinct from ACE inhibition.

RPYL confirmed AT1 receptor blocker
The lactoferrin-derived peptide RPYL directly inhibited angiotensin II binding to AT1 receptors in radioligand assays, a mechanism shared with prescription ARB drugs

What the researchers found

Lactoferrin-derived peptides, including LfcinB20-25 (RRWQWR), LIWKL, and RPYL, all inhibited angiotensin II-induced vasoconstriction in ex vivo assays. RPYL showed the highest inhibitory effect and was confirmed to directly block AT1 receptor binding using radioligand assays with [(125)I]-(Sar(1),Ile(8))-angiotensin II.

Importantly, neither the lactoferrin hydrolysate nor RPYL inhibited endothelin-1 or depolarization-induced vasoconstriction, demonstrating selectivity for the angiotensin pathway. This represents a blood pressure-lowering mechanism beyond ACE inhibition that may work synergistically with it.

Why it matters

Most food-derived blood pressure-lowering peptides work by inhibiting ACE (the enzyme that makes angiotensin II). This study reveals that lactoferrin peptides can also block angiotensin receptors directly — the same mechanism used by prescription ARB drugs like losartan. Having multiple mechanisms of action could make lactoferrin-derived peptides more effective as natural blood pressure support.

How the study worked

The study used ex vivo vascular tissue assays to test lactoferricin B-derived peptide (LfcinB20-25), a low molecular weight lactoferrin hydrolysate (<3 kDa), and two peptides identified within the hydrolysate (LIWKL and RPYL) for their ability to inhibit vasoconstriction induced by angiotensin II, endothelin-1, or depolarization. RPYL was further tested in radioligand receptor binding assays to confirm direct AT1 receptor blockade.

What this study cannot tell us

This is an ex vivo study using isolated vascular tissue, not a whole-animal or human study. The peptides' oral bioavailability and ability to reach blood vessels intact after digestion is unknown. Concentrations used in tissue assays may not reflect achievable physiological levels. Only a limited number of peptide sequences were tested from the lactoferrin hydrolysate.

How to read the evidence

This is a preclinical mechanistic study using ex vivo vascular tissue assays and radioligand binding. While the methodology is rigorous for identifying receptor-level mechanisms, the findings are far from clinical application without in vivo and human data.

When this study was published

Published in 2014, this study is over a decade old. It remains a key reference for the angiotensin receptor blocking activity of lactoferrin-derived peptides, a mechanism that has been further explored in subsequent research.

The bigger picture

Food-derived bioactive peptides are a growing area of functional food and nutraceutical research. Most work has focused on ACE-inhibitory peptides, but this study opens a parallel pathway — angiotensin receptor blockade. Lactoferrin is already commercially available as a supplement, and understanding its peptide fragments' mechanisms could lead to targeted formulations for blood pressure management.

Questions still open

Can the peptide RPYL survive digestion and reach the bloodstream in sufficient concentrations to block AT1 receptors in vivo?
Do the dual mechanisms (ACE inhibition + AT1 receptor blockade) of lactoferrin peptides produce additive blood pressure effects in animal models or humans?
Could lactoferrin-derived peptides be developed into a natural alternative or complement to prescription ARB medications?

Common questions

What is lactoferrin and where do these peptides come from?

Lactoferrin is an iron-binding protein found naturally in milk, saliva, and other body fluids. When lactoferrin is digested or broken down in the lab, it produces smaller peptide fragments. Some of these fragments have biological activities, including the ability to lower blood pressure by interacting with the same receptors targeted by prescription blood pressure medications.

How is angiotensin receptor blocking different from ACE inhibition?

ACE inhibitors prevent the body from making angiotensin II (the hormone that constricts blood vessels), while angiotensin receptor blockers (ARBs) allow angiotensin II to be made but prevent it from working by blocking its receptor. This study shows lactoferrin peptides can do both — a dual mechanism that could provide stronger blood pressure support.

Read the original research

Antihypertensive mechanism of lactoferrin-derived peptides: angiotensin receptor blocking effect.

Journal of agricultural and food chemistry, 62(1), 173-81

View on PubMed ↗Publisher’s paper ↗

Citation

Fernández-Musoles, Ricardo; Castelló-Ruiz, María; Arce, Cristina; Manzanares, Paloma; Ivorra, M Dolores; Salom, Juan B. (2014). Antihypertensive mechanism of lactoferrin-derived peptides: angiotensin receptor blocking effect.. Journal of agricultural and food chemistry, 62(1), 173-81. https://doi.org/10.1021/jf404616f