Lin_2026_Foods_15_

Plant-derived bioactive peptides have garnered widespread interest for their functions in managing obesity and associated metabolic disorders. This study investigated the lipid-lowering activity and underlying mechanisms of VPIIMH, a hexapeptide derived from Chlorella pyrenoids, using in vitro enzymatic assays, Caenorhabditis elegans models, and network pharmacology. In vitro, VPIIMH acted as a reversible non-competitive inhibitor of pancreatic lipase, achieving an inhibition rate of 43.17 +/- 1.47% at 8.0 mg/mL. Molecular docking revealed that this inhibition likely occurs through ionic bonds between VPIIMH and PL (1LPB) at Arg256. In a high-fat C. elegans model, treatment with 0.5 mg/mL VPIIMH significantly reduced fat accumulation by 37.2% and triglyceride levels by 26.9%. Furthermore, VPIIMH extended the lifespan of C. elegans under oxidant stress by 40.3% and under heat stress by 17.5%. Network pharmacology predicted that VPIIMH targets nine core proteins, which were classified into three synergistic modules: the SIRT1-PPAR for core regulation, the RAS for systemic coordination, and the inflammatory target (CCR5, MMP9, EGFR) for microenvironment support. This study elucidates the multi-target and multi-pathway mechanism of VPIIMH, suggesting its potential application in combating obesity and related lipid metabolism disorders. These findings provide a scientific basis for the development of VPIIMH as a functional food ingredient targeting metabolic health.