Identification and characterization of antihypertensive peptides from edible Grifola frondosa (maitake) mushroom hydrolysates: Suppression of vascular remodeling in angiotensin II-induced zebrafish model

Grifola frondosa (maitake), a widely consumed edible fungus with documented cardiovascular benefits, is rich in protein and serves as a valuable natural source for bioactive peptide production. Despite its potential, studies on blood pressure-lowering peptides derived from G. frondosa are limited. In this study, we enzymatically hydrolyzed G. frondosa proteins to generate ACE inhibitory peptides, followed by chromatographic separation and purification. Peptidomics-based high-throughput sequencing was used to analyze fractions with potent ACE inhibitory activity, leading to the identification of eight novel peptide sequences (APPLRP, LPPLL, LPPLLL, LPPLPRP, LPPPLLK, LPPRLP, LPPRP, and RPPLP). These peptides were selected based on their amino acid positional characteristics, ADMET properties, and cross-referencing with established databases. Molecular docking analysis revealed that APPLRP and LPPLPRP exhibited the strongest ACE binding affinity, suggesting their superior inhibitory potential. Furthermore, network pharmacology elucidated the mechanistic pathways underlying the antihypertensive effects of these peptides, particularly their role in mitigating angiotensin II-induced vascular remodeling in a zebrafish model. • Peptidomics combined with virtual screening were used to confirm the ACE-inhibitory peptides in GfH. • ACE inhibitory peptide of GfH exhibits X -Pro-Pro- Y type with amino acid composition. • Molecular docking and network pharmacology reveals potential targets of peptides APPLRP and LPPLPRP. • APPLRP and LPPLPRP attenuated vascular remodeling in an Ang II-induced zebrafish model.