Hyaluronic acid in vivo serves a multitude of functions, including water retention and osmoregulation. Inhibition of hyaluronidase activity prevents the degradation of hyaluronic acid, thereby preserving its normal physiological functions. Fucoidan is a natural sulfated polysaccharide extracted from brown algae. Here, bovine testicular hyaluronidase was separated and purified as a basis for investigating the inhibitory effect of fucoidan on hyaluronidase activity. The experimental results showed that fucoidan exhibited strong competitive inhibition of hyaluronidase activity, with an IC50 value of 4.137 μM. Molecular docking demonstrated that fucoidan binds to the active site of hyaluronidase, with its sulfate groups forming hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations suggested that the complex formed by the binding of fucoidan to hyaluronidase was highly stable, with a binding energy of -24.59 kcal/mol, indicating a high affinity between fucoidan and hyaluronidase. The Ramachandran plot indicated that the binding of fucoidan to hyaluronidase results in a structural change in the active site of the enzyme, making its structure more inert and compact.
Keywords: activity; fucoidan; hyaluronidase; inhibition; interaction; molecular mechanism.