Taxifolin prevents postprandial hyperglycemia by regulating the activity of α‐amylase: Evidence from an in vivo and in silico studies

Abstract

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Hesperidin improves insulin resistance via down-regulation of inflammatory responses: Biochemical analysis and in silico validation

“…Elevated levels of these enzymes in serum, shows abnormal functioning of the liver. In HFDinduced obesity, the increased level of AST and ALT may indicate the uncontrolled and irregular metabolic function of the liver [40,54]. In present findings, hesperidin alone and in combination with orlistat has shown to regulate the serum levels of AST (P<0.001) and ALT (P<0.001) when compared with that of HFD group (Fig 4A and 4B).…”

“…The treatment of hesperidin showed its potential for lowering the serum levels of cholesterol, TGs and LDL, whereas the serum level of HDL was improved. These results were found to be corresponding in terms of anti-lipidemic effects of many plants oriented bioactive flavonoids [40,54].…”

“…Each complex was immersed into an octahedron box of the TIP3P [38] water model of 12 Å dimension at 300 K temperature and 1 bar pressure. Each system of the protein-protein and protein-ligand complex was then subjected to production simulations run of 50 ns following the same protocol and parameters as those reported in our previous publications [39,40]. All MD simulations were carried out using the CARNAL, ANAL, and PTRAJ modules of AMBER16.…”

Mechanism of Action of Mangifera indica Leaves for Anti-Diabetic Activity

“…However, in some cases, high levels of blood glucose due to excess activity of alpha-amylase results in hyperglycemia [15]. Thus, the inhibition of alpha-amylase activity can reduce postprandial hyperglycemia and prevent the risk of diabetes development [16,17]. In this study, ethanol extract of M. indica leaves (MIL) was investigated for its capability against alpha-amylase activity.…”

Repellency, Toxicity, Gene Expression Profiling and In Silico Studies to Explore Insecticidal Potential of Melaleuca alternifolia Essential Oil against Myzus persicae

“…For further refinement and stabilization in solution systems, each of the top ranked docking-simulated structural model (terpinen-4-ol- OSD , terpinen-4-ol- FPPS I and terpinen-4-ol- HSP 60 ) complexes was subjected to MD simulations for 40 nanoseconds (ns). All MD simulations and molecular mechanics-based free energy calculations (MM/PB(GB)SA) [ 50 ], were entirely carried out in the AMBER16 software package [ 51 ], following the same protocol and parameters as those reported in our previous publications [ 48 , 49 , 52 ].…”