ABSTRACT
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 IC
ABSTRACT
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 IC 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 IC 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.
ABSTRACT
The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii×Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling (p-Akt(Ser473) and p-PKC-ζ/λ(Thr410/403)), p-AMPK(Thr172) and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-α and nuclear NF-κB) as well as p-PKC-θ(Thr538) were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.