Two Blood Pressure-Lowering Peptides Discovered in Pumpkin Seed Meal Survive Digestion and Protect Blood Vessels | Research

The takeaway

Two novel peptides from pumpkin seed meal inhibited ACE, upregulated protective ACE2, improved blood vessel cell function, and survived simulated digestion — making pumpkin seeds a promising source of natural blood pressure-lowering compounds.

IC₅₀ = 90.69 μM
The pumpkin seed peptide PVQVLASAYR's ACE inhibitory potency, combined with ACE2 upregulation and vascular protection, represents a multi-mechanism approach to blood pressure reduction

What the researchers found

Two peptides were identified with ACE inhibitory activity: SNHANQLDFHP (IC₅₀ = 172.07 μM) and PVQVLASAYR (IC₅₀ = 90.69 μM). Molecular docking showed both interact with ACE through hydrogen bonds and hydrophobic interactions.

In endothelial cells (EA.hy926), both peptides decreased endothelin-1 secretion (a vasoconstrictor), increased nitric oxide release (a vasodilator), and upregulated ACE2 activity (the protective arm of the renin-angiotensin system). Both peptides showed good stability against simulated gastrointestinal enzyme digestion, supporting potential oral bioavailability.

Why it matters

Pumpkin seed meal is currently a waste product of the oil industry. Discovering that it contains bioactive peptides with multiple blood pressure-lowering mechanisms — ACE inhibition, ACE2 upregulation, and direct vascular protection — could add significant value to this agricultural byproduct while providing natural alternatives or supplements for hypertension management.

How the study worked

Pumpkin seed meal hydrolysate was prepared using Neutrase 5.0 BG enzyme. Peptides were isolated and purified through ultrafiltration, Sephadex G-15 chromatography, and RP-HPLC. ACE inhibition was measured in vitro. Molecular docking modeled peptide-ACE interactions. Endothelial cell assays measured endothelin-1, nitric oxide, and ACE2 activity. Simulated gastrointestinal digestion tested stability.

What this study cannot tell us

All findings are from in vitro experiments and computational modeling — no animal or human studies have confirmed blood pressure-lowering effects. The IC₅₀ values are higher than pharmaceutical ACE inhibitors, so clinical significance is uncertain. Simulated digestion may not fully represent in vivo conditions. Actual oral bioavailability in living organisms was not measured.

How to read the evidence

This is a preclinical in vitro study combining enzyme assays, molecular docking, cell culture, and simulated digestion. While the multi-method approach provides strong mechanistic evidence, no in vivo or clinical studies have been conducted.

When this study was published

Published in 2024, this study reflects the current state of food-derived bioactive peptide research with modern molecular docking and cell-based validation techniques.

The bigger picture

Food-derived ACE inhibitory peptides are an increasingly researched class of bioactive compounds that could bridge the gap between nutrition and pharmacology. This study stands out because the peptides don't just block ACE — they also upregulate protective ACE2 and directly improve vascular function, providing a triple mechanism of action that drug-based ACE inhibitors don't offer.

Questions still open

Do these pumpkin seed peptides actually lower blood pressure when consumed as food or supplements in humans?
How does the combined ACE inhibition plus ACE2 upregulation compare to pharmaceutical ACE inhibitors in vascular protection?
Could pumpkin seed meal be processed into a standardized supplement with reliable blood pressure-lowering peptide content?

Common questions

Can eating pumpkin seeds lower blood pressure?

This study found that specific peptides in pumpkin seed meal can inhibit ACE and protect blood vessels in laboratory tests, and that these peptides survive simulated digestion. However, whether eating pumpkin seeds in normal dietary amounts would meaningfully lower blood pressure has not been tested in humans. The research supports the potential for pumpkin seed-based supplements, but clinical studies are needed before making health claims.

Why is ACE2 upregulation important alongside ACE inhibition?

ACE and ACE2 have opposing effects in blood pressure regulation. ACE produces angiotensin II, which constricts blood vessels and raises pressure. ACE2 converts angiotensin II into Ang(1-7), which relaxes vessels and lowers pressure. By simultaneously inhibiting ACE (blocking the harmful pathway) and upregulating ACE2 (boosting the protective pathway), these peptides offer a dual-action approach that pharmaceutical ACE inhibitors alone don't provide.

Read the original research

Two Novel Angiotensin-Converting Enzyme (ACE) Inhibitory and ACE2 Upregulating Peptides from the Hydrolysate of Pumpkin (Cucurbita moschata) Seed Meal.

Journal of agricultural and food chemistry, 72(19), 10909-10922

View on PubMed ↗Publisher’s paper ↗

Citation

Li, Xin; Peng, Chenghai; Xiao, Suyao; Wang, Qun; Zhou, Aimei. (2024). Two Novel Angiotensin-Converting Enzyme (ACE) Inhibitory and ACE2 Upregulating Peptides from the Hydrolysate of Pumpkin (Cucurbita moschata) Seed Meal.. Journal of agricultural and food chemistry, 72(19), 10909-10922. https://doi.org/10.1021/acs.jafc.4c00609