In vitro,in vivo andin silico anti-hyperglycemic inhibition by sinigrin

Objective:To evaluate the anti-hyperglycemic potential of sinigrin usingin vitro,in silico and in vivo streptozotocin (STZ) induced hyperglycemic zebrafish model.Methods: Thein vitro enzyme inhibition assay was carried out to determine the IC50 value againstα-glucosidase andα-amylase,in silico molecular docking was performed against both enzymes with PyRx tool and simulations were performed using GROMACS tool. Hyperglycemia was induced in zebrafishes using three intraperitoneal injections on alternating days for one week at 350 mg/kg of STZ. Hyperglycemic fishes were treated intraperitoneally with 50, 100 and 150 mg of sinigrin/kg of body weight for 24 h and glucose levels were measured.Results:The sinigrin showed very strong inhibition againstα-glucosidase andα-amylase with 0.248 and 0.00124 μM while reference drug acarbose showed IC50 value of 73.0700 and 0.0017 μM againstα-glucosidase andα-amylase, respectively. Kinetic analysis revealed that sinigrin has the mixed type mode of inhibition againstα-glucosidase. Molecular docking results revealed its strong binding affinity withα-glucosidase (-10.00 Kcal/mol) andα-amylase (-8.10 Kcal/mol). Simulations graphs confirmed its stability against both enzymes. Furthermore, in hyperglycemic zebrafishes most significant (P