Chaetomorpha linum (O.F.Müller) Kützing 1845 attenuates glucotoxicity via modulation of polyol pathway, oxidative stress and glucose metabolism in adipose tissue

Chronic hyperglycaemia in type 2 diabetes drives a self-perpetuating cycle of glucotoxicity. This study investigated the therapeutic potential of extracts from the green seaweed Chaetomorpha linum (O.F.Müller) Kützing, 1845 to mitigate glucotoxicity in rats adipocytes. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed distinct phytochemical profiles, with the aqueous extract containing isolobinine, kurarinol, rutaevin, and proanthocyanidin-A2, and the ethanol extract containing caryoptin, mesembrinol, 12-deoxyphorbol-13-octadecanoate, and aspulvinone H. Bioactivity assays showed that C. linum extracts reversed glucotoxicity-induced pathologies, restoring glucose uptake (3.9–6.1 mg/g adipose tissue at 240 µg/mL), suppressing polyol pathway enzyme activities (2.7–9.5 µmol/min/mg, at 240 µg/mL), and enhancing antioxidant defense markers. Concurrently, the extracts inhibited key digestive enzymes (26.7–41.0 µmol/min/µL, at 240 µg/mL). Molecular docking supported these findings, with rutaevin showing the high affinity for aldose reductase (−11.7 kcal/mol) and proanthocyanidin-A2 for lipase (−9.9 kcal/mol) and glutathione peroxidase (−7 kcal/mol). These findings highlight C. linum as a promising source of bioactive compounds for diabetes management.