Abstract / Summary
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, which, together with associated metabolic abnormalities, contributes to progressive damage in multiple organ systems. The development of effective and safe therapeutic alternatives remains a major research priority. Phlorizin is a dihydrochalcone that inhibits sodium-glucose cotransporter 1 and 2 (SGLT1 and SGLT2). 4‐ortho‐mono‐fructosyl phlorizin (4PHF) was synthesized from phlorizin by transfructosylation with a levansucrase from Paraburkholderia phymatum (KesL) using sucrose as a donor. The in vivo antidiabetic effect of 4PHF was evaluated using a murine model of experimental diabetes (high-fat diet followed by a single streptozotocin dose). Groups were treated as follows for 28 days: Non-Diabetic control group received only distilled water; a group receiving 4PHF, and a group treated with a SGLT2 inhibitor, dapagliflozin. 4PHF exhibited a tendency to reduce blood glucose levels, increased urinary glucose excretion, improved lipid profile by lowering triglycerides and total cholesterol. Histologically, 4PHF showed clear hepatoprotective and renoprotective effects. Immunohistochemistry revealed a marked decrease in SGLT2 expression and in the number of SGLT2-positive tubules in treated animals, suggesting that the treatment may modulate SGLT2 inhibition. Overall, 4PHF emerges as a promising therapeutic candidate for diabetes mellitus, as it reduces renal SGLT2 expression, improves metabolic dysfunction, and attenuates diabetes-induced hepatic and renal damage.