A possible alternative therapy for type 2 diabetes using Myristica fragrans Houtt in combination with glimepiride: In vivo evaluation and in silico support

Abstract

The current study aimed to evaluate the in vivo hypoglycemic potential of Myristica fragrans seed extract co-administered with glimepiride in Swiss albino mice. Computational tools were used to further verify the in vivo findings and to help compare this combination to the glimepiride-pioglitazone combination in terms of the binding affinity of the ligands to their respective target protein receptors and the relative stability of the drug-protein complexes. The effect of the combined therapy was observed both in alloxan- and glucose-induced hyperglycemic Swiss albino mice. The mean fasting blood glucose level of the test groups was measured and statistically evaluated using Student's t test. The combined therapy significantly reduced the blood glucose level in a time-dependent manner compared to glimepiride alone. The binding affinity of glimepiride was found to be -7.6 kcal/mol with sulfonylurea receptor 1 in molecular docking. Conversely, macelignan-peroxisome proliferator-activated receptor (PPAR) α and macelignan-PPAR γcomplexes were stabilized with -9.2 and -8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γcomplexes were more stable than pioglitazone complexes. The combination shows promise in animal and computer models and requires further trials to provide evidence of its activity in humans.