Wheat-Derived Peptides Lower Blood Pressure in Hypertensive Rats Through Multiple Mechanisms | Research

The takeaway

Wheat oligopeptides achieved 77% ACE inhibition and significantly reduced blood pressure in hypertensive rats by combating oxidative stress, inflammation, and organ damage.

77% ACE inhibition
Wheat oligopeptides at 2.5 mg/mL blocked more than three-quarters of ACE enzyme activity in vitro

What the researchers found

Wheat oligopeptides (WOPs) demonstrated potent ACE inhibitory activity, achieving 77% inhibition at 2.5 mg/mL, and produced marked reductions in systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MBP) in spontaneously hypertensive rats.

The peptides worked through multiple mechanisms: activating the Nrf2/Keap1 pathway to reduce oxidative stress in kidneys and heart tissue, lowering serum levels of six inflammatory markers (TNF-α, IL-6, IL-1β, ET-1, VEGF-A, CD62E), and modulating the PI3K/AKT signaling pathway along with AT1R, ACE, and eNOS signaling proteins to protect organ tissue from hypertension-related damage.

Why it matters

Hypertension affects over a billion people worldwide and is a leading cause of heart disease, stroke, and kidney failure. While synthetic ACE inhibitors are effective, they carry side effects. Food-derived peptides that lower blood pressure through multiple complementary mechanisms — ACE inhibition, anti-inflammation, and antioxidant protection — could offer a gentler, more holistic approach through functional foods.

How the study worked

Wheat oligopeptides were produced by enzymatic hydrolysis of wheat protein. ACE inhibitory activity was measured in vitro. In vivo experiments used spontaneously hypertensive rats (SHRs) — a well-established animal model for essential hypertension. Blood pressure was measured over the treatment period. Kidney and heart tissues were examined for oxidative stress and inflammation markers. Signaling pathway activation was assessed through molecular analysis of relevant proteins.

What this study cannot tell us

This is an animal study using a specific rat model of hypertension; results may not directly translate to humans. The exact peptide sequences responsible for the antihypertensive effects were not individually identified. Dosing, bioavailability, and long-term safety in humans have not been evaluated. No comparison with standard antihypertensive drugs was reported.

How to read the evidence

This is a preclinical animal study using a well-established hypertension model. The in vivo results with mechanistic data are stronger than pure in vitro studies, but human clinical evidence is needed.

When this study was published

Published in 2025, this is a very recent study contributing to the growing evidence base for food-derived antihypertensive peptides.

The bigger picture

Food-derived antihypertensive peptides are a rapidly growing research area as consumers and healthcare systems seek natural approaches to managing blood pressure. While most prior work has focused on milk- and fish-derived peptides, this study highlights wheat as a promising and widely available source. The multi-mechanistic action — beyond simple ACE inhibition — sets wheat oligopeptides apart from many food-derived alternatives.

Questions still open

Which specific peptide sequences within the wheat oligopeptide mixture are responsible for the blood-pressure-lowering effects?
Do wheat oligopeptides survive human digestion intact enough to exert antihypertensive activity?
How would the blood-pressure-lowering effect of WOPs compare to standard ACE inhibitor drugs in a head-to-head animal study?

Common questions

What are wheat oligopeptides and how are they made?

Wheat oligopeptides are short chains of amino acids produced by breaking down wheat protein with enzymes. They are small enough to potentially be absorbed in the gut and exert biological effects. The process is similar to how the body digests protein, but it is done in a controlled laboratory setting.

Could wheat peptides replace blood pressure medication?

Not based on current evidence. This study was conducted in rats, and it is unknown whether the same effects would occur in humans. Even if confirmed in clinical trials, food-derived peptides would more likely complement, rather than replace, conventional medications — potentially as part of functional foods for people with mildly elevated blood pressure.

Read the original research

Antihypertensive effects and mechanisms of wheat oligopeptides in spontaneously hypertensive rats.

Journal of the science of food and agriculture, 105(15), 8935-8946

View on PubMed ↗Publisher’s paper ↗

Citation

Liu, Wenying; Wang, Xinze; Meng, Ganlu; Yang, Chengjun; Zhang, Xinxue. (2025). Antihypertensive effects and mechanisms of wheat oligopeptides in spontaneously hypertensive rats.. Journal of the science of food and agriculture, 105(15), 8935-8946. https://doi.org/10.1002/jsfa.70135