Administration of oleuropein or hydroxytyrosol improves diabetic markers in obese mice

Context: Olive leaves are renowned for their medicinal properties in managing diabetes, primarily due to their high concentrations of hydroxytyrosol andoleuropein.Aims: To evaluate the anti-diabetic effects of hydroxytyrosol and oleuropein isolates in a mice model of obesity-induced diabetes.Methods: Male Swiss Webster mice were subjected to a high-fat diet and streptozotocin to induce obesity and diabetes, respectively. Following induction, themice were treated with either oleuropein or hydroxytyrosol at a dosage of 20 mg/kg body weight over a period of 14 days. Fasting glucose levels, insulinsensitivity, and glucose tolerance were monitored throughout the treatment period. Additionally, histological examinations of the liver and pancreas wereconducted. Furthermore, in silico docking studies were performed to assess the interactions of oleuropein and hydroxytyrosol with key metabolic receptors,including peroxisome proliferator-activated receptor gamma (PPARγ), hydroxysteroid 11-β dehydrogenase 1 (HSD11B1), and fructose-bisphosphatase 1(FBP1).Results: Treatment with oleuropein and hydroxytyrosol led to significant reductions in fasting blood glucose levels and marked improvements in insulinsensitivity in obese and diabetic mice. These compounds also provided protective effects against pancreatic and hepatic cellular damage. In silico analysescorroborated these findings, demonstrating strong binding affinities of oleuropein and hydroxytyrosol to the targeted receptors.Conclusions: Oleuropein and hydroxytyrosol exhibit potent anti-diabetic effects in vivo, comparable to those of metformin, including glucose regulation,improved insulin sensitivity, and cellular protection. These findings suggest their potential as therapeutic agents for managing type 2 diabetes and itsassociated complications.