Sulfated galactans from Gracilaria corticata reprogram metabolism, activate Immunity, promote regeneration, and exhibit anti-melanoma activity.

Sulfated polysaccharides from marine algae hold therapeutic potential, but their mechanisms remain underexplored. This study investigates how distinct sulfated galactans from the red seaweed Gracilaria corticata reprogram cellular metabolism to drive specific biological responses. Six fractions (GC-1A/B, GC-2A/B, GC-3A/B) obtained by sequential cold and hot extraction were structurally characterized using NMR and FTIR. Cold-extracted fractions (GC-1A/B) enhanced macrophage phagocytosis and nitric oxide production, indicating immunostimulation. Hot-extracted fractions (GC-2A/3A) promoted human skin cell proliferation and migration while inhibiting B16-F10 melanoma cell growth. Targeted metabolomics revealed that these effects arise from cell-type-specific metabolic reprogramming, including changes in amino acid and lipid profiles. In skin cells, the active fractions also increased antioxidant enzyme activity and modulated wound healing genes. These findings establish sulfated galactans as metabolic modulators whose bioactivity depends on the extraction method. This work provides a framework for developing marine polysaccharides into targeted therapies for immune disorders, tissue regeneration, and cancer.