Spirulina derived peptides: Inhibition mechanism on pancreatic lipase and impact on lipid-lowering effects of Caenorhabditis elegans.

This study aimed to optimize the enzymatic hydrolysis process of Spirulina protein (SP) using pepsin. By employing a combined approach that includes sequencing, virtual screening, and in vitro and in vivo experiments, we investigated the inhibitory mechanism of pancreatic lipase (PL) and its effects on lipid accumulation in Caenorhabditis elegans (C. elegans). Optimal hydrolysis conditions were determined to be pH 1.8, an enzyme concentration of 3100 U/g, and an enzymolysis time of 2.6 h, resulting in Spirulina protein hydrolysate (SPH) that demonstrated significant PL inhibition (37.52 ± 1.05 %) through mixed-type inhibition kinetics. HPLC-Q Exactive-MS and bioinformatics analyses identified five active peptides (LPLL, FLGF, YPFW, YYGR, FLQR) with IC50 values ranging from 1.1997 to 1.8566 mg/mL, which are comparable to Orlistat (0.99197 mg/mL). These peptides interact with PL through both polar and non-polar interactions, including hydrogen bonding and hydrophobic interactions, which stabilize the peptide-PL complex. Furthermore, they significantly reduced lipid accumulation in C. elegans. This study demonstrates that Spirulina peptides extracted via pepsin hydrolysis inhibit PL activity and reduce lipid accumulation in C. elegans, suggesting their potential as functional food ingredients or dietary supplements for weight management.