Iranian Journal of

Background: Diabetes mellitus is recognized as a complex metabolic syndrome primarily characterized by elevated blood glucose levels (hyperglycemia). α-glucosidase, located in the microvilli of the small intestine, play a pivotal role in the hydrolysis of complex carbohydrates into absorbable monosaccharides. However, the use of common chemical inhibitors of this enzyme, such as metformin, is frequently associated with undesirable side effects. The present research aims to evaluate the inhibitory potential of compounds isolated from Fumaria officinalis on α-glucosidase activity, utilizing computational (in silico) approaches.
Methods: This study was designed and executed with a descriptive-analytical approach, based on computational methodologies. Initially, the 3D structures of key compounds identified from Fumaria officinalis were retrieved from the PubChem database. Simultaneously, the crystal structure of the α-glucosidase was downloaded from the Protein Data Bank (PDB). The toxicity profile of the compounds was predicted using Toxtree and Protox II tools, and drug-likeness properties, based on Lipinski’s rules, were assessed via the SwissADME server. Finally, molecular docking studies were conducted to investigate the interactions between the enzyme and the compounds of interest, employing AutoDock Tools 1.5.6 and Molegro Virtual Docker 6.0 software. Analysis of the molecular interactions resulting from docking was performed with Discovery Studio 3.5 software.
Results: The findings of this research indicate that all selected compounds from Fumaria officinalis, while adhering to Lipinski’s rules and showing no predicted toxicity, exhibited favorable binding energies, positioning them as potential candidates for α-glucosidase inhibition. Among the evaluated compounds, Fumaricine and Chlorogenic Acid demonstrated the lowest binding energies, -7.18 and -7.83 kcal/mol, respectively, thus exhibiting the highest inhibitory potential compared to other compounds. Notably, the binding energies of these two compounds were significantly more negative than that of the standard inhibitor, metformin, indicating their stronger binding affinity to the enzyme’s active site.
Conclusion: Based on the results obtained from this computational study, it can be inferred that Fumaricine and Chlorogenic Acid, as the most prominent compounds found in Fumaria officinalis, act as more effective inhibitors due to their ability to form stronger hydrogen and hydrophobic interactions with key amino acids in the α-glucosidase enzyme’s active site. Therefore, it is suggested that further in vitro and in vivo studies be conducted on these compounds to comprehensively validate their potential in the prevention and management of diabetes mellitus.