Prediction of the Potential Mechanism Underlying the Anti-Inflammatory Effect of MAAs Identified from Sargassum sp. Extracts: A Zebrafish and Molecular Docking Study

Background/Objectives: Excessive inflammation harms the host, and conventional anti-inflammatory drugs have limitations. Seaweed-derived bioactive substances have become a focus in anti-inflammatory research, yet studies on the anti-inflammatory effects of mycosporine-like amino acids (MAAs) from Sargassum remain scarce. Methods: A zebrafish inflammation model was used to evaluate the anti-inflammatory activity and safety of Sargassum-derived MAA extracts. Isolation and identification were conducted to confirm the MAA monomers, and molecular docking was applied to analyze the binding characteristics of two monomers (mycosporine-NMA-Thr, palythine) with anti-inflammatory targets, compared with dexamethasone. Results: At 100 μg/mL, the MAA extracts significantly reduced the number of immune cells surrounding zebrafish neuromasts, demonstrating clear anti-inflammatory activity. However, its safe concentration was only 25 μg/mL, highly overlapping with the effective anti-inflammatory concentration (≥ 50 μg/mL), and toxicity was presumably from impurities. The extracts contained palythine and mycosporine-NMA-Thr (first isolated from Sargassum sp.). Both monomers had docking energies < −7.0 kcal/mol with their targets (comparable stability to dexamethasone), with mycosporine-NMA-Thr showing better binding affinity to arhgef and palythine to naglu, along with target selectivity. Conclusions: Sargassum sp. exhibits significant anti-inflammatory activity. The palythine and mycosporine-NMA-Thr isolated from Sargassum sp. exhibit broad-spectrum binding capacities toward multiple anti-inflammatory targets, providing promising candidate molecules for the development of natural anti-inflammatory agents.