Molecular Docking Analysis of Selected Phytochemicals Targeting GLP-1R, GIPR, and DPP4

Obesity and Type 2 diabetes mellitus (T2DM) are becoming major health concerns worldwide, with 890 million people being obese as of 2022 [1]. Recently developed drugs to treat T2DM have shown remarkable results in weight loss, proving them-selves as efficient tools in fighting obesity. They are also called GLP-1 agonists, because they mimic the action of the natural glucagon-like peptide-1 a hormone that regulates blood sugar by stimulating insulin secretion. However, these medications are extreme-ly expensive, so recent studies are focusing on finding natural alternatives that could be more affordable. In silico studies are computer simulations on how molecules inter-act, and may save a lot of experimental work by giving indications on which com-pounds could be effective for a given purpose. The present study carried out molecular docking on selected phytochemicals with reported roles in weight management and their interactions with GLP-1 receptors, as well as gastric inhibitory polypeptide re-ceptors (GIPR) and Dipeptidyl Peptidase-4 (DPP4). The selected molecules were: ber-berine, chlorogenic acid, curcumin, epigallocatechin gallate (EGCG), hesperidin, quer-cetin and rutin. The molecular docking results show that EGCG, hesperidin and rutin may have some good affinity with the GLP-1 receptor, berberine, hesperidin and rutin to DPP4, while none of the selected molecules had significant affinity to the GIP re-ceptor. However, these phytochemicals have much smaller molecules than the syn-thetic peptides that are used in the treatment of T2DM and obesity, so they may well bind to other receptors too and have little selectivity and specificity. The ADME profile indicates berberine as the most promising candidate for drug development. Further studies are needed to investigate if these molecules have practical application in the treatment of obesity and how they could be used.