Neuroprotective Potential of the Edible Seaweed Pterocladiella capillacea: Bioactivity Coupled LC-MS/MS, Metabolomics Annotation, Validation, and Network Pharmacology

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a global impact, highlighting an urgent need for effective dietary therapeutic agents for the development of brain-healthy functional foods and medicines. This study focuses on the edible red alga Pterocladiella capillacea from Zhanjiang, China, investigating its anti-neuronal injury activity, active principles, and underlying mechanisms. Methods: Based on antioxidant and neuroprotection evaluations and column fractioning, bioactivity-coupled liquid chromatography-tandem mass spectrometry (Bio-LC-MS/MS) was employed to recognize the neuroprotective compounds, which were further annotated by comprehensive metabolomics analysis. The annotated compounds were validated by LC-MS/MS and bioassay. Computational prediction techniques were further used to reveal their mechanism of action. Results: The study demonstrated that P. capillacea extract and fractions exhibited significant antioxidant and anti-neuronal injury activities. Among the annotated and MS-validated potential compounds, erucamide standard exhibited the strongest neuroprotective effect, maintaining cell viability above 85% at low concentrations. Network pharmacology and molecular docking revealed that erucamide may exert neuroprotective effects by modulating the AKT1 and BCL2 targets. ADMET prediction suggested a low risk of central side effects. Conclusions: The neuroprotective potential of P. capillacea provides a primary foundation for new brain-healthy functional foods and drug development in future.