Natural Products as Prominent Source of Bioactive Components with Anti-diabetic Potential

Abstract

Type 2 diabetes (T2DM) is a chronic metabolic condition characterized by elevated blood sugar levels. It is caused by a combination of insulin resistance and insulin production impairment. The nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is essential for glucose homeostasis and lipid metabolism. PPAR-g agonists are a family of medicines used to manage type 2 diabetes by improving blood sugar management and enhancing insulin sensitivity. For decades, natural materials have been utilized as traditional remedies, and many of them have been demonstrated to have anti-diabetic properties. Some natural compounds have been proven in recent investigations to activate PPAR-g. We employed molecular docking and physicochemical screening in this investigation to discover natural compounds with the potential to be developed as novel anti-diabetic medicines. A library of more than 50 natural compounds was tested against the PPAR-g ligand binding domain. We also assessed the ADMET and physicochemical features of the compounds found to determine that they are drug-like. Our study shows the Drug-likeness, bioactivity score along with good ADMEt profile of various phytoconstituents with their high binding affinity toward PPAR-g (PDB ID: 2XKW) as a major target for T2DM. Physicochemical properties of selected compounds were done with SWISS ADME server while ADMEt screening was done by pkCSM server. The binding affinity and molecular interaction study of natural compounds with PPAR-g was done by using Molegro Virtual Docker (MVD). The MolDock and Rerank score of the top one compound of each category was taken to check the binding interaction with tubulin.