Determination of interactions of antidiabetic plants with glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors by in silico analysis

Type 2 diabetes mellitus stands as the most prevalent variant of diabetes, presenting a myriad of complications that profoundly diminish the quality of life for affected individuals and elevate the risk of premature mortality. Furthermore, those grappling with this condition frequently endure a range of adverse social, economic, and psychological repercussions. In response to this pressing health challenge, a diverse array of treatment modalities, founded upon distinct mechanisms of action, have been developed and continue to be explored. The overarching aims of such interventions are to achieve optimal glycemic control, avert potential complications, enhance the quality of life, and mitigate early mortality rates. Among these therapeutic strategies, incretin-based therapies hold particular significance, as they harness the body's innate processes by emulating the secretion mechanisms of GIP and GLP-1 from the pancreas. In parallel to these established treatments, there has been a burgeoning interest in herbal-based medicines, which have garnered increasing attention in recent years. In the present study, we undertook the identification of plants and phytochemical compounds possessing antidiabetic properties, specifically those native to Turkey. To this end, we employed molecular docking analysis—a pivotal approach in the realms of drug design and development—to scrutinize the interactions between these plant-derived compounds and the protein targets associated with GLP-1 receptor agonists and DPP-4 inhibitors utilized in incretin-based therapies. The results of our molecular docking analysis yielded an impressive 1.740 candidate molecules for GLP-1 and 818 candidate molecules for DPP-4. Subsequent SwissADME analysis of these candidates revealed that 864 were situated within the bioavailability radar for GLP-1, while 228 were identified for DPP-4. A more granular examination of the candidate molecules targeting DPP-4 ultimately revealed 36 distinct compounds derived from 13 different plant sources. These findings suggest a promising potential for these molecules in the treatment of diabetes, as demonstrated through in silico methodologies. In conclusion, this study successfully identified a total of 36 phytochemicals from 13 plants endowed with antidiabetic potential through a rigorous comparative analysis of 1.914 phytochemicals and existing antidiabetic pharmacotherapies, thus contributing valuable insights into the quest for novel drug candidates.