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

Objective: To evaluate the anti-hyperglycemic potential of sinigrin using in vitro, in silico and in vivo streptozotocin (STZ) induced hyperglycemic zebrafish model. Methods: The in vitro enzyme inhibition assay was carried out to determine the IC50 value against alpha-glucosidase and alpha-amylase, in silico molecular docking was performed against both enzymes with PyRx tool and simulations were performed using GROMACS tool. Hyperglycemia was induced in zebralishes 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 against alpha-glucosidase and alpha-amylase with 0.248 and 0.001 24 mu M while reference drug acarbose showed IC50, value of 73.0700 and 0.0017 mu M against alpha-glucosidase and alpha-amylase, respectively. Kinetic analysis revealed that sinigrin has the mixed type mode of inhibition against alpha-glucosidase. Molecular clocking results revealed its strong binding affinity with alpha-glucosidase (-10.00 Kcal/mol) and alpha-amylase (-8.10 Kcal/mol). Simulations graphs confirmed its stability against both enzymes. Furthermore, in hyperglycemic zebrafishcs most significant (P<0.001) reduction of glucose was occurred at 150 mg/kg, moderate significant reduction of glucose was observed at 100 mg/kg and no any significant reduction of glucose was measured at 50 mg/kg. Conclusions: It can be evident from the present results that sinigrin has potent anti-hyperglycemic activity and it may prove to be effective treatment for the hyperglycemia.