<i>trans</i>-Tiliroside and (+)-pinoresinol: polyphenols against albumin glycation, α-glucosidase activity and ROS formation, with <i>in silico</i> pharmacokinetic evaluation

<i>trans</i>-Tiliroside and (+)-pinoresinol, a flavonoid and a lignan found in plants traditionally used for diabetes mellitus care, were investigated for antidiabetic properties through <i>in vitro</i> and <i>in silico</i> studies. Four assays were conducted: Bovine Serum Albumin (BSA) assay to assess inhibition of albumin glycation, α-glucosidase assay to evaluate decrease of carbohydrate digestion, Oxygen Radical Absorbance Capacity (ORAC) assay for antioxidant activity and cytotoxicity evaluation on HT-29 cells. <i>trans</i>-Tiliroside showed higher inhibition of protein glycation, with IC₅₀ values of 113.6, 71.03 and 95.73 µM against glucose, fructose and ribose-induced glycation, respectively. Moreover, <i>trans</i>-tiliroside demonstrated higher antioxidant capacity than (+)-pinoresinol. Both compounds showed slight α-glucosidase inhibitory activity and no cytotoxicity in HT-29 cells at 0.1–100 µM. An <i>in silico</i> pharmacokinetic study evaluated their bioavailability. Results suggest <i>trans</i>-tiliroside can act as an inhibitor of protein glycation, potentially reducing unwanted glycation reactions and preventing hyperglycaemia-related diseases.