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 γ complexes were stabilized with −9.2 and −8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γ complexes 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.
List of abbreviations
- PPAR
peroxisome proliferator-activated receptor
- SUR 1
sulfonylurea receptor 1
- MD
molecular dynamics
- T2DM
type 2 diabetes mellitus
- SUs
sulfonylureas
- GPD
glimepiride
- MFSE
Myristica fragrans seed extract
- MLN
macelignan
- OGTT
oral glucose tolerance test
- PDB
Protein Data Bank
- RMSD
root-mean-square deviation
Acknowledgments
The authors would like to thank the Department of Pharmacy, University of Asia Pacific, for the laboratory facilities. Special thanks to Prof. Dr. Mohiuddin Ahmed Bhuiyan, former head, Department of Pharmacy, University of Asia Pacific, for his kind cooperation during the project.
Funding: This research did not receive any specific grant from agencies in public, commercial, or not-for-profit sector.
Availability of data and material: The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.
Ethical approval and consent to participate: The study protocol for laboratory animal use and care was approved by Institutional Research Ethics Committee, University of Asia Pacific, Bangladesh, and the ARRIVE guidelines.
Consent for publication: Not applicable.
Competing interests: The authors declare that they have no competing interests.
Authors’ contributions: WN developed the original idea and protocol, and participated in data analysis and manuscript writing. SS and FADMO participated in laboratory work and literature review. MAS performed computational study and manuscript editing. RA performed data abstraction. MS reviewed the manuscript for data presentation. MAH analyzed the computational study. All authors read and approved the final manuscript.
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