A marine ACE inhibitory peptide SLPWPMKPMNLIE exerts neuroprotective effects associated with RAS-related signaling in SH-SY5Y cells

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With growing demand for functional foods, the multi-dimensional regulatory effects and molecular associations of food-derived bioactive molecules have drawn increasing attention. Here, we report that SLPWPMKPMNLIE, a potential hypotensive peptide from Pinctada martensii with ACE inhibitory capacity, protects SH-SY5Y cells against MPP + /Ang II-induced neurotoxicity. The peptide attenuated oxidative stress damage, restored mitochondrial membrane potential, and mitigated iron deposition in SH-SY5Y cells. These neuroprotective effects were accompanied by alterations in renin-angiotensin system related markers: expression of ACE and AGTR1 was downregulated, while the protective MAS1 was upregulated, in parallel with the restored expression of neurotrophic factors. These findings suggest a possible association between the observed neuroprotection and modulation of RAS-related signaling. Overall, this study provides preliminary insights into the potential of shellfish-derived ACE inhibitory peptides in alleviating hypertension-related neuronal injury, and highlights the need for future mechanistic validation.