Antihypertensive effects and mechanisms of wheat oligopeptides in spontaneously hypertensive rats

Hypertension is a significant risk factor for heart disease, stroke, and chronic kidney disease. Wheat oligopeptides (WOPs), small peptide mixtures derived from the enzymatic hydrolysis of wheat protein, contain peptides of varying molecular weights. Although previous studies have shown that plant-derived protein peptides can lower blood pressure, systematic research on WOPs and their antihypertensive mechanisms remains relatively limited. The aim of this study was to evaluate the antihypertensive efficacy of WOPs kDa and to investigate its mechanisms.

The study found that WOPs demonstrated potent angiotensin-converting enzyme (ACE) inhibitory activity, achieving a 77% inhibition rate at 2.5 mg·mL^-1, and that they induced marked reductions in diastolic (DBP), systolic (SBP), and mean arterial (MBP) blood pressure in spontaneously hypertensive rats (SHRs). WOPs reduced oxidative stress-induced damage in the kidneys and myocardium of the SHR by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway. They also lowered serum levels of inflammatory factors in SHRs: tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), endothelin-1 (ET-1), vascular endothelial growth factor A (VEGF-A), and cluster of differentiation 62E (CD62E). WOPs also alleviated kidney and myocardial tissue damage caused by hypertension through the activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and regulation of angiotensin II type 1 receptor (AT1R), ACE, and endothelial nitric oxide synthase (eNOS) signaling proteins, thereby contributing to blood pressure regulation.

WOPs demonstrated notable antihypertensive effects in vivo. These results may provide a theoretical basis for further investigation of the in vivo antihypertensive mechanisms of WOPs and support their potential use in pharmaceutical and functional food development. © 2025 Society of Chemical Industry.