Novel Potent Decameric Peptide of Spirulina platensis Reduces Blood Pressure Levels Through a PI3K/AKT/eNOS-Dependent Mechanism

Considered as a superfood of the future, Spirulina platensis matrix has been extensively used because of its beneficial effect on the management of cardiovascular diseases. However, its nutraceutical properties, bioactive compounds, and molecular mechanisms are unknown. Here, we demonstrate that S platensis matrix processed in vitro by simulated gastrointestinal digestion induces direct endothelial nitric oxide (NO)-mediated vasorelaxation of resistance vessels in mice. To gain insight into the bioactive compounds responsible for this effect, we used a complex multistep peptidomic approach to fractionate the crude digest: of the 5 peptide fractions identified (A–E), only fraction E evoked vasorelaxation. High-resolution mass spectrometry–based screening revealed in E the presence of 4 main peptides (SP3–SP6 [spirulina peptides]), of which only SP6 (GIVAGDVTPI) exerted direct endothelium-dependent vasodilation of ex vivo vessels, an effect occurring via a PI3K (phosphoinositide-3-kinase)/AKT (serine/threon...