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 α-glucosidase and α-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 1 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 α-glucosidase and α-amylase with 0.248 and 0.00124 μM while reference drug acarbose showed IC₅₀ value of 73.0700 and 0.0017 μM against α-glucosidase and α-amylase, respectively. Kinetic analysis revealed that sinigrin has the mixed type mode of inhibition against α-glucosidase. Molecular docking results revealed its strong binding affinity with α-glucosidase (-10.00 kcal/mol) and α-amylase (-8.10 kcal/mol). Simulations graphs confirmed its stability against both enzymes. Furthermore, in hyperglycemic zebrafishes 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.