LC-HRMS-Based Metabolomic Profiling and Antioxidant Activity of Sargassum ilicifolium Under Different Pretreatments, Extraction Methods, and Solvents.

Sargassum is a widespread brown seaweed species and a source of bioactive compounds with promising antioxidant potential. Unfortunately, to date, the Sargassum species remains largely unexplored. This study was conducted to explore the bioactive compounds from Sargassum ilicifolium extracts collected from Nguyahan and Sundak Beaches, Gunungkidul, Indonesia, by observing Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS)-based metabolomics profiling and antioxidant activity assays. Metabolomic analysis detected 506 molecular features across different extraction methods and solvents, with five metabolites putatively dereplicated, including atractylenolide III, pheophorbide A, 13-docosenamide, 1,3,6,8-tetrahydroxy-2-(1-hydroxyhexyl)anthracene-9,10-dione, and 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid. Extraction parameters, particularly solvent polarity and sample pretreatment, have been shown to affect the metabolite variation. Dried samples showed less variation in metabolites than the fresh sample. Antioxidant activity assay showed a moderate to high radical scavenging activity (30-100%), with methanol extracts as a polar solvent inhibited more than semipolar solvents. This study provides a metabolomics-guided assessment of the antioxidant potential of S. ilicifolium, supporting its value and potential as a source of bioactive compounds for future pharmaceutical and nutraceutical applications.