Neuroprotective Potential of Peptide KSVSPKFLTG from Magallana gigas via Activating the ACE2/Ang-(1-7)/Mas Axis in SHSY-5Y Cells

Given the growing demand for health-promoting foods, there is increasing interest in the multi-dimensional regulatory effects and the mechanisms of food-derived bioactives. Here, we report that KSVSPKFLTG, an anti-inflammatory peptide from Magallana gigas with ACE2-binding properties, protects SHSY-5Y cells against MPP+/FAC-induced neurotoxicity. The peptide attenuates oxidative stress damage in SHSY-5Y cells and improves the mitochondrial membrane potential. It also mitigates iron overload and upregulates ferroptosis-related protective proteins (GPX4, SLC7A11, BCBP2, SLC40A1) via activating the renin–angiotensin system. These findings reveal an RAS-modulating neuroprotective mechanism of the oyster-derived anti-inflammatory peptide, simultaneously opening new avenues for alleviating nerve damage caused by inflammation through bioactive peptides.