The use of seaweeds as functional foods and drugs is well known. Capsosiphon fulvescens (C. fulvescens) is a green sea algafor which
beneficial health impacts have been reported even in diabetes. In the present study, three C. fulvescens constituents (chalinasterol,
capsofulvesin A and capsofulvesin B) were evaluated for their molecular binding signature and interaction patterns against human
aldose reductase as an antidiabetic target. The enzyme has been robustly implicated in the development of secondary complications
of diabetes. The results generated here with the aid of in silico tools revealed a favourable binding affinity for the seawed constituents
on the active site of aldose reductase. However, detailed observation shows no interference with the NADP binding pocket. The binding
configuration of capsofulvesin A and capsofulvesin B were comparable to fidarestatas the compounds inserted one of their elongated
aliphatic long chains with double bondsinto the binding pocket. Nonetheless, subtle differences were sighted with the binding format
of the aliphatic chain of capsofulvesin B resulting froma possiblehydrophobic hinderanceor influence within the binding pocket. Only
one of the aliphatic chainsof capsofulvesin A enjoyed hydrophobic interaction with residues Val47, Trp219 and Phe122 compared to the
capsofulvesin B having hydrophobic interaction with Phe122 at the second chain while the other aliphatic chain formed hydrophobicbond
with Trp20, Val47, Trp219 and Leu300. Meanwhile, the galactoseunit of the two compounds displayed similar binding orientation and
interaction with amino acid residues Ser22 and Trp20 at the active site. Chalinasterol, on the other hand, established hydrogen bond
with the imidazole ring of His110 and indole ring of Trp111 respectively. The current study represents the first attempt to model the
interaction of these ligands with aldose reductase and theunique bindingpatterns might explain the mechanism and potency of C.
fulvescens in themanagement of diabetes and its complications.