In silico evaluation of macroalgae specific carbohydrates for antioxidant, anti-inflammatory and antiglycemic...

Seaweeds represent a rich source of bioactive carbohydrates and complex polysaccharides with promising applications in managing oxidative stress, inflammation and glycemic control as a sustainable treatment of diabetes mellitus. This study employed an in silico approach to evaluate the therapeutic potential of all twelve major macroalgae specific carbohydrates. Disaccharide units of the macroalgal carbohydrate polymers were designed, energy-minimised, screened for drug-likeness and bioactivity in order to identify the shared targets for antioxidant, anti-inflammatory and antiglycemic activities with these ligands. The predicted protein targets were integrated with disease-associated genes and protein-protein interaction networks were constructed to validate and understand the metabolic functions. Drug-likeness and bioactivity indicated favourable pharmacokinetic and therapeutic properties. Enrichment analyses revealed that ligands modulate diverse biological processes linked to oxidative stress mitigation, inflammatory regulation and glucose metabolism. From the docked ligands, monomeric sugar ligands of β1→6 laminarin and ulvan B exhibited the highest binding affinities with multiple key targets, followed by fucoidan, ulvan A, alginate and κ-, ι- and λ-carrageenans that showed substantial interactions. Notably, dihydrofolate reductase (DHFR), and Harvey rat sarcoma viral oncogene homolog (HRAS) were identified as promising targets for antiglycemic activity and glutathione reductase (GSR) were linked to both antioxidant and antiglycemic activities. Renin (REN) showed selective affinity with κ-carrageenan in the anti-inflammatory pathway and angiotensin converting enzyme (ACE) appeared as a common promiscuous target across all three activities. These findings highlight the potential of seaweed-derived sugars to modulate key regulatory proteins and signalling pathways, suggesting their promising role as natural, multi-functional therapeutic agents for managing oxidative, inflammatory and metabolic disorders.