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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.<\/jats:p>","DOI":"10.3390\/nu18193210","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:12:42Z","timestamp":1790669562000},"page":"3210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Potential of the Edible Seaweed Pterocladiella capillacea: Bioactivity Coupled LC-MS\/MS, Metabolomics Annotation, Validation, and Network Pharmacology"],"prefix":"10.3390","volume":"18","author":[{"given":"Meicai","family":"Yue","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Shenzhen Institute of Guangdong Ocean University, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-4073","authenticated-orcid":false,"given":"Longjian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological 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Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-684X","authenticated-orcid":false,"given":"Zhiyou","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Shenzhen Institute of Guangdong Ocean University, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic 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