First comprehensive in vitro and in silico investigations of the antidiabetic activity of Cladostephus spongiosus (Cladostephaceae): from marine ecosystem to biological application

Cladostephus spongiosus is a brown alga belonging to the family Cladostephaceae, known for its diverse array of bioactive compounds and broad spectrum of biological activities. This work provides the first comprehensive evaluation of its antidiabetic potential using complementary in vitro and in silico approaches. Five extracts obtained with solvents of increasing polarity were evaluated for their inhibitory activity against the key carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. In parallel, nine compounds previously identified from these extracts were investigated through molecular docking, binding interaction analysis, molecular dynamics simulations, and ADMET predictions to elucidate their potential contribution to the observed biological activity. Among the tested extracts, the ethanol extract exhibited the strongest dual antidiabetic activity, showing α-glucosidase inhibition of 4.28 mmol ACAE/g extract, α-amylase inhibition of 0.54 mmol ACAE/g extract in the iodine assay, and an IC₅₀ value of 9.73 µg/mL in the DNSA assay. Computational analyses revealed favorable interactions and stable binding profiles for several compounds, particularly loliolide, isololiolide, herniarin, and monocrotaline isomer, highlighting their potential role in enzyme inhibition. Overall, the findings identify C. spongiosus as a promising marine source of bioactive compounds with potential applications in antidiabetic drug discovery.